From 64dc79bf54bfed0792ca0ae0f297e8385fb05180 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Tue, 28 May 2024 15:07:06 +0100 Subject: [PATCH 01/17] [Platform] Add Profile and ProfileHeader to variant page (#376) --- .../platform/src/pages/VariantPage/Header.tsx | 2 +- .../src/pages/VariantPage/Profile.tsx | 13 +++ .../src/pages/VariantPage/ProfileHeader.tsx | 92 +++++++++++++++++++ .../src/pages/VariantPage/VariantPage.tsx | 65 +++++++++---- apps/platform/src/pages/VariantPage/index.js | 2 - apps/platform/src/pages/VariantPage/index.ts | 1 + apps/platform/src/pages/VariantPage/types.ts | 28 +++--- 7 files changed, 169 insertions(+), 34 deletions(-) create mode 100644 apps/platform/src/pages/VariantPage/Profile.tsx create mode 100644 apps/platform/src/pages/VariantPage/ProfileHeader.tsx delete mode 100644 apps/platform/src/pages/VariantPage/index.js create mode 100644 apps/platform/src/pages/VariantPage/index.ts diff --git a/apps/platform/src/pages/VariantPage/Header.tsx b/apps/platform/src/pages/VariantPage/Header.tsx index 9cabe1cde..58b7a6f3b 100644 --- a/apps/platform/src/pages/VariantPage/Header.tsx +++ b/apps/platform/src/pages/VariantPage/Header.tsx @@ -5,7 +5,7 @@ import { MetadataType } from "./types"; type HeaderProps = { loading: boolean; metadata: MetadataType; -} +}; function Header({ loading, metadata }: HeaderProps) { const { diff --git a/apps/platform/src/pages/VariantPage/Profile.tsx b/apps/platform/src/pages/VariantPage/Profile.tsx new file mode 100644 index 000000000..7be750c7d --- /dev/null +++ b/apps/platform/src/pages/VariantPage/Profile.tsx @@ -0,0 +1,13 @@ +import ProfileHeader from "./ProfileHeader"; + +type ProfileProps = { + varId: string; +}; + +function Profile({ varId }: ProfileProps) { + + return + +} + +export default Profile; \ No newline at end of file diff --git a/apps/platform/src/pages/VariantPage/ProfileHeader.tsx b/apps/platform/src/pages/VariantPage/ProfileHeader.tsx new file mode 100644 index 000000000..7a1036cfa --- /dev/null +++ b/apps/platform/src/pages/VariantPage/ProfileHeader.tsx @@ -0,0 +1,92 @@ +import { useState, useEffect } from "react"; +import { Field, ProfileHeader as BaseProfileHeader } from "ui"; +import { Box, Typography } from "@mui/material"; +import { InSilicoPredictorsType, MetadataType } from "./types"; + +type ProfileHeaderProps = { + varId: string; +}; + +function ProfileHeader({ varId }: ProfileHeaderProps) { + + // temp: data will come from gql, fetch local json file for now + const [metadata, setMetadata] = + useState("waiting"); + useEffect(() => { + fetch("../data/variant-data-2.json") + .then(response => response.json()) + .then((allData: MetadataType[]) => + setMetadata(allData.find(v => v.variantId === varId))); + }, []); + + // temp: always set loading to false for now + const loading = false; + + // temp: revisit this (use same as other pages) once using gql to get data + if (!metadata) { + return Metadata not found! + } else if (metadata === "waiting") { + return Waiting; + } + + return ( + + + + Location + + {metadata.chromosome}:{metadata.position} + + + {metadata.referenceAllele} + + + {metadata.alternateAllele} + + Variant Effect Predictor (VEP) + + {metadata.vep.mostSevereConsequence.replace(/_/g, ' ')} + + + + + Population Allele Frequencies + + {metadata.alleleFrequencies + .map(({populationName, alleleFrequency }) => ( + + + + + )) + } +
+ + {populationLabels[populationName as keyof typeof populationLabels]} + + + + {alleleFrequency.toFixed(3)} + +
+ + + + ) +} + +export default ProfileHeader; + +// !! NEEDS CHECKED SINCE DIFFERENT KEYS TO THOSE USED ON CURRENT VARIANT PAGE +const populationLabels = { + afr_adj: 'African/African-American', + amr_adj: 'Latino/Admixed American', + asj_adj: 'Ashkenazi Jewish', + eas_adj: 'East Asian', + fin_adj: 'Finnish', + nfe_adj: 'Non-Finnish European', + ami_adj: 'Non-Finnish European Estonian', + mid_adj: 'Non-Finnish European North-Western European', + sas_adj: 'Non-Finnish European Southern European', + remaining_adj: 'Other (population not assigned)', +}; \ No newline at end of file diff --git a/apps/platform/src/pages/VariantPage/VariantPage.tsx b/apps/platform/src/pages/VariantPage/VariantPage.tsx index bb26f5183..8cf8f648a 100644 --- a/apps/platform/src/pages/VariantPage/VariantPage.tsx +++ b/apps/platform/src/pages/VariantPage/VariantPage.tsx @@ -1,34 +1,40 @@ - -import { useState, useEffect } from "react"; -import { useLocation, useParams } from "react-router-dom"; -import { BasePage } from "ui"; +import { useState, useEffect, lazy, Suspense } from "react"; +import { + useLocation, + useParams, + Switch, + Route, + useRouteMatch, + Link, +} from "react-router-dom"; +import { Box, Tabs, Tab } from "@mui/material"; +import { BasePage, ScrollToTop, LoadingBackdrop } from "ui"; import Header from "./Header"; import NotFoundPage from "../NotFoundPage"; import { MetadataType } from "./types"; -// const Profile = lazy(() => import("./Profile")); +const Profile = lazy(() => import("./Profile")); function VariantPage() { const location = useLocation(); const { varId } = useParams() as { varId: string }; - const [metadata, setMetadata] = - useState('waiting'); - - // temp: loading is set by useQuery, set to false for now - const loading = false; + const { path } = useRouteMatch(); // temp: data will come from gql, fetch local json file for now - useEffect(() => { - fetch('../data/variant-data-2.json') - .then(response => response.json()) - .then((allData: MetadataType[]) => - setMetadata(allData.find(v => v.variantId === varId))); - }, []); + const [metadata, setMetadata] = useState("waiting"); + useEffect(() => { + fetch("../data/variant-data-2.json") + .then(response => response.json()) + .then((allData: MetadataType[]) => setMetadata(allData.find(v => v.variantId === varId))); + }, []); + + // temp: loading is set by useQuery, set to false for now + const loading = false; // temp: revisit this (use same as other pages) once using gql to get data if (!metadata) { return ; - } else if (metadata === 'waiting') { + } else if (metadata === "waiting") { return Waiting; } @@ -39,8 +45,31 @@ function VariantPage() { location={location} >
+ + ( + + + Profile} + value={`/variant/${varId}`} + component={Link} + to={`/variant/${varId}`} + /> + + + )} + /> + }> + + + + + + ); } -export default VariantPage; \ No newline at end of file +export default VariantPage; diff --git a/apps/platform/src/pages/VariantPage/index.js b/apps/platform/src/pages/VariantPage/index.js deleted file mode 100644 index 8c8d16086..000000000 --- a/apps/platform/src/pages/VariantPage/index.js +++ /dev/null @@ -1,2 +0,0 @@ -// export { default } from "./VariantPage"; -export {default} from "./VariantPage" diff --git a/apps/platform/src/pages/VariantPage/index.ts b/apps/platform/src/pages/VariantPage/index.ts new file mode 100644 index 000000000..88b3b52cc --- /dev/null +++ b/apps/platform/src/pages/VariantPage/index.ts @@ -0,0 +1 @@ +export { default } from "./VariantPage"; diff --git a/apps/platform/src/pages/VariantPage/types.ts b/apps/platform/src/pages/VariantPage/types.ts index d398d0782..24c24585d 100644 --- a/apps/platform/src/pages/VariantPage/types.ts +++ b/apps/platform/src/pages/VariantPage/types.ts @@ -1,4 +1,4 @@ -type AlleleFrequencyType = { +export type AlleleFrequencyType = { populationName: string; alleleFrequency: number; }; @@ -12,6 +12,19 @@ type VepType = { }[]; }; +export type InSilicoPredictorsType = { + cadd?: { + phred: number; + raw: number; + }; + revelMax?: number; + spliceaiDsMax?: number; + pangolinLargestDs?: number; + phylop?: number; + siftMax?: number; + polyphenMax?: number; +}; + export type MetadataType = { variantId: string, chromosome: string, @@ -24,16 +37,5 @@ export type MetadataType = { alleleType: string; alleleFrequencies: AlleleFrequencyType[]; vep: VepType; - inSilicoPredictors: { - cadd?: { - phred: number; - raw: number; - }; - revelMax?: number; - spliceaiDsMax?: number; - pangolinLargestDs?: number; - phylop?: number; - siftMax?: number; - polyphenMax?: number; - }; + inSilicoPredictors: InSilicoPredictorsType; }; \ No newline at end of file From eed3ac4732f5107124503709d7a6e9b59ceb2135 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Tue, 28 May 2024 15:27:47 +0100 Subject: [PATCH 02/17] [Platform]: variant page widgets init (#380) --- .../src/pages/VariantPage/Profile.tsx | 61 +- apps/platform/src/pages/VariantPage/types.ts | 60 +- apps/platform/src/sections/variantSections.js | 7 + packages/sections/src/variant/EVA/Body.tsx | 2964 +++++++++++++++++ .../sections/src/variant/EVA/Description.tsx | 18 + packages/sections/src/variant/EVA/Summary.tsx | 42 + packages/sections/src/variant/EVA/index.ts | 16 + .../src/variant/InSilicoPredictors/Body.tsx | 135 + .../InSilicoPredictors/Description.tsx | 18 + .../variant/InSilicoPredictors/Summary.tsx | 42 + .../src/variant/InSilicoPredictors/index.ts | 11 + .../src/variant/UniProtVariants/Body.tsx | 289 ++ .../variant/UniProtVariants/Description.tsx | 18 + .../src/variant/UniProtVariants/Summary.tsx | 42 + .../src/variant/UniProtVariants/index.ts | 11 + 15 files changed, 3731 insertions(+), 3 deletions(-) create mode 100644 apps/platform/src/sections/variantSections.js create mode 100644 packages/sections/src/variant/EVA/Body.tsx create mode 100644 packages/sections/src/variant/EVA/Description.tsx create mode 100644 packages/sections/src/variant/EVA/Summary.tsx create mode 100644 packages/sections/src/variant/EVA/index.ts create mode 100644 packages/sections/src/variant/InSilicoPredictors/Body.tsx create mode 100644 packages/sections/src/variant/InSilicoPredictors/Description.tsx create mode 100644 packages/sections/src/variant/InSilicoPredictors/Summary.tsx create mode 100644 packages/sections/src/variant/InSilicoPredictors/index.ts create mode 100644 packages/sections/src/variant/UniProtVariants/Body.tsx create mode 100644 packages/sections/src/variant/UniProtVariants/Description.tsx create mode 100644 packages/sections/src/variant/UniProtVariants/Summary.tsx create mode 100644 packages/sections/src/variant/UniProtVariants/index.ts diff --git a/apps/platform/src/pages/VariantPage/Profile.tsx b/apps/platform/src/pages/VariantPage/Profile.tsx index 7be750c7d..d8707401b 100644 --- a/apps/platform/src/pages/VariantPage/Profile.tsx +++ b/apps/platform/src/pages/VariantPage/Profile.tsx @@ -1,12 +1,71 @@ +import { Suspense, lazy } from "react"; +import { + // PlatformApiProvider, + SectionContainer, + SummaryContainer, + SectionLoader, +} from "ui"; + +import InSilicoPredictorsSummary from "sections/src/variant/InSilicoPredictors/Summary"; +import EVASummary from "sections/src/variant/EVA/Summary"; +import UniProtVariantsSummary from "sections/src/variant/UniProtVariants/Summary"; + import ProfileHeader from "./ProfileHeader"; +const InSilicoPredictorsSection = lazy(() => import("sections/src/variant/InSilicoPredictors/Body")); +const EVASection = lazy(() => import("sections/src/variant/EVA/Body")); +const UniProtVariantsSection = lazy(() => import("sections/src/variant/UniProtVariants/Body")); + +const summaries = [ + InSilicoPredictorsSummary, + EVASummary, + UniProtVariantsSummary +]; + +const VARIANT = "variant"; + +// !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! +// TO DO (see e.g. profile.jsx for the evidence page): +// - VARIANT_PROFILE_SUMMARY_FRAGMENT +// - EVIDENCE_PROFILE_QUERY +// !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! + type ProfileProps = { varId: string; }; function Profile({ varId }: ProfileProps) { - return + return ( + // !!!!!!!!!! + // PUT EVERYTHING INSIDE INSTEAD OF FRAGMENT + // !!!!!!!!!! + <> + + + + + + + + + + + }> + + + }> + + + }> + + + {/* NEED ANYTHING IN ???? see evidence page */} + + + + + ); } diff --git a/apps/platform/src/pages/VariantPage/types.ts b/apps/platform/src/pages/VariantPage/types.ts index 24c24585d..3e3de5f40 100644 --- a/apps/platform/src/pages/VariantPage/types.ts +++ b/apps/platform/src/pages/VariantPage/types.ts @@ -1,3 +1,8 @@ + +// ======== +// Metadata +// ======== + export type AlleleFrequencyType = { populationName: string; alleleFrequency: number; @@ -37,5 +42,56 @@ export type MetadataType = { alleleType: string; alleleFrequencies: AlleleFrequencyType[]; vep: VepType; - inSilicoPredictors: InSilicoPredictorsType; -}; \ No newline at end of file +}; + +// ================== +// InSilicoPredictors +// ================== + +export type InSilicoPredictorsType = { + [index: number]: { + method: string, + assesessment?: string, + flag?: string, + score?: number, + } +}; + +// ======= +// ClinVar +// ======= + +export type ClinVarType = { + alleleOrigins: string[], + alleleRequirements: string[], + approvedSymbol: string, + clinicalSignificances: string[], + cohortPhenotypes: string[], + confidence: string, + directionOnTrait: "risk", + "disease.id": string, + "disease.name": string, + diseaseFromSource: string, + diseaseId: string, + diseaseName: string, + literature: string[], + studyId: string, + targetId: string, + variantId: string, +}; + +// =============== +// UniProtVariants +// =============== + +export type UniProtVariants = { + variantId: string, + confidence: string, + diseaseFromSource: string, + literature: string[], + targetFromSourceId: string, + "target.id": string, + "target.approvedSymbol": string, + "disease.id": string, + "disease.name": string, +}; diff --git a/apps/platform/src/sections/variantSections.js b/apps/platform/src/sections/variantSections.js new file mode 100644 index 000000000..6332e4972 --- /dev/null +++ b/apps/platform/src/sections/variantSections.js @@ -0,0 +1,7 @@ +import { lazy } from "react"; + +const variantSections = new Map([ + ["eva", lazy(() => import("sections/src/evidence/EVA/Body"))], +]); + +export default variantSections; diff --git a/packages/sections/src/variant/EVA/Body.tsx b/packages/sections/src/variant/EVA/Body.tsx new file mode 100644 index 000000000..4a222b85e --- /dev/null +++ b/packages/sections/src/variant/EVA/Body.tsx @@ -0,0 +1,2964 @@ +import { + Link, + Tooltip, + SectionItem, + PublicationsDrawer, + DataTable, + ClinvarStars, +} from "ui"; +import { Typography } from "@mui/material"; +import { + clinvarStarMap, + naLabel, + defaultRowsPerPageOptions, +} from "../../constants"; +import { definition } from "."; + +import Description from "./Description"; +import { epmcUrl } from "../../utils/urls"; +import { sentenceCase } from "../../utils/global"; + +// !! NEEDED?? +const onLinkClick = e => { + // handler to stop propagation of clicks on links in table rows + // to avoid selection of a different row + e.stopPropagation(); +}; + +function getColumns(label: string) { + return [ + { + id: "disease.name", + label: "Disease/phenotype", + renderCell: (d) => { // !! DESTRUCTURE AS NORMAL WHEN USE GQL WITHOUT THESE ODD PROPERTY NAMES + const disease_id = d["disease.id"] + const disease_name = d["disease.name"]; + const { diseaseFromSource, cohortPhenotypes } = d; + return ( + + + Reported disease or phenotype: + + + {diseaseFromSource} + + {cohortPhenotypes?.length > 1 ? ( + <> + + All reported phenotypes: + + + {cohortPhenotypes.map(cp => ( +
{cp}
+ ))} + + + ) : ( + "" + )} + + } + showHelpIcon + > + {/* !! ANY !! as any needed below since onClick sig expects no args !! */} + + {disease_name} + + + ) + }, + exportLabel: "Disease/Phenotype", + exportValue: disease_name => disease_name, + filterValue: disease_name => disease_name, + }, + { + id: "studyId", + label: "ClinVar ID", + renderCell: ({ studyId }) => + studyId ? ( + + {studyId} + + ) : ( + naLabel + ), + exportLabel: "ClinVar ID", + }, + { + id: "clinicalSignificances", + label: "Clinical significance", + renderCell: ({ clinicalSignificances }) => { + if (!clinicalSignificances) return naLabel; + if (clinicalSignificances.length === 1) return sentenceCase(clinicalSignificances[0]); + if (clinicalSignificances.length > 1) + return ( +
    + {clinicalSignificances.map(clinicalSignificance => ( +
  • {sentenceCase(clinicalSignificance)}
    • + ))} +
+ ); + return naLabel; + }, + filterValue: ({ clinicalSignificances }) => clinicalSignificances.join(), + }, + { + id: "allelicRequirements", + label: "Allele origin", + renderCell: ({ alleleOrigins, allelicRequirements }) => { + if (!alleleOrigins || alleleOrigins.length === 0) return naLabel; + if (allelicRequirements) + return ( + + + Allelic requirements: + + {allelicRequirements.map(r => ( + + {r} + + ))} + + } + showHelpIcon + > + {alleleOrigins.map(a => sentenceCase(a)).join("; ")} + + ); + return alleleOrigins.map(a => sentenceCase(a)).join("; "); + }, + filterValue: ({ alleleOrigins }) => (alleleOrigins ? alleleOrigins.join() : ""), + }, + { + id: "reviewStatus", + label: "Review status", + renderCell: ({ confidence }) => ( + + + + + + ), + }, + { + id: "literature", + label: "Literature", + renderCell: ({ literature }) => { + const literatureList = + literature?.reduce((acc, id) => { + if (id !== "NA") { + acc.push({ + name: id, + url: epmcUrl(id), + group: "literature", + }); + } + return acc; + }, []) || []; + return ( + + ); + }, + }, + ]; +} + +// !!!! LOAD LOCAL DATA FOR NOW +// const [metadata, setMetadata] = +// useState("waiting"); +const request = mockQuery(); + +type BodyProps = { + id: string, + label: string, + entity: string, +}; + +function Body({ id, label, entity }: BodyProps) { + + const columns = getColumns(label); + const rows = request.data.variant.eva; + + return ( + } + renderBody={() => ( + + )} + /> + ); + +} + +export default Body; + + +// !! HARDCODE DATA FOR NOW !! +function mockQuery() { + return { + loading: false, + error: undefined, + data: JSON.parse(` +{ + "variant": { + "eva": [ + { + "alleleOrigins": [ + "germline", + "maternal", + "paternal" + ], + "allelicRequirements": [ + "Autosomal recessive inheritance" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Diffuse cerebral degeneration in infancy", + "Infantile poliodystrophy", + "Mitochondrial DNA Depletion Syndrome 4A", + "Mitochondrial DNA depletion syndrome 4A (Alpers type)", + "Neuronal degeneration of childhood with liver disease, progressive", + "Poliodystrophia cerebri progressiva", + "Progressive cerebral poliodystrophy", + "Progressive sclerosing poliodystrophy" + ], + "confidence": "criteria provided, multiple submitters, no conflicts", + "directionOnTrait": "risk", + "disease.id": "MONDO_0008758", + "disease.name": "mitochondrial DNA depletion syndrome 4a", + "diseaseFromSource": "Progressive sclerosing poliodystrophy", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "literature": [ + "11431686", + "11571332", + "12565911", + "14694057", + "15122711", + "15477547", + "15824347", + "16130100", + "16177225", + "17426723", + "19251978", + "21276947", + "26942291", + "26942292", + "632821" + ], + "studyId": "RCV000014443", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "alleleOrigins": [ + "germline", + "maternal", + "paternal" + ], + "allelicRequirements": [ + "Autosomal recessive inheritance" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Diffuse cerebral degeneration in infancy", + "Infantile poliodystrophy", + "Mitochondrial DNA Depletion Syndrome 4A", + "Mitochondrial DNA depletion syndrome 4A (Alpers type)", + "Neuronal degeneration of childhood with liver disease, progressive", + "Poliodystrophia cerebri progressiva", + "Progressive cerebral poliodystrophy", + "Progressive sclerosing poliodystrophy" + ], + "confidence": "criteria provided, multiple submitters, no conflicts", + "directionOnTrait": "risk", + "disease.id": "Orphanet_726", + "disease.name": "Alpers syndrome", + "diseaseFromSource": "Progressive sclerosing poliodystrophy", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "literature": [ + "11431686", + "11571332", + "12565911", + "14694057", + "15122711", + "15477547", + "15824347", + "16130100", + "16177225", + "17426723", + "19251978", + "21276947", + "26942291", + "26942292", + "632821" + ], + "studyId": "RCV000014443", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "alleleOrigins": [ + "germline", + "maternal", + "paternal" + ], + "allelicRequirements": [ + "Autosomal recessive inheritance" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Epilepsy, progressive myoclonic, type 5", + "SENSORY ATAXIC NEUROPATHY WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE", + "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome" + ], + "confidence": "criteria provided, multiple submitters, no conflicts", + "directionOnTrait": "risk", + "disease.id": "MONDO_0011835", + "disease.name": "sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "diseaseFromSource": "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "literature": [ + "11431686", + "11571332", + "12565911", + "14694057", + "15122711", + "15477547", + "15824347", + "16130100", + "16177225", + "17426723", + "19251978", + "21276947", + "26942291", + "26942292", + "632821" + ], + "studyId": "RCV000014441", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "alleleOrigins": [ + "germline", + "maternal", + "paternal" + ], + "allelicRequirements": [ + "Autosomal recessive inheritance" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Epilepsy, progressive myoclonic, type 5", + "SENSORY ATAXIC NEUROPATHY WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE", + "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome" + ], + "confidence": "criteria provided, multiple submitters, no conflicts", + "directionOnTrait": "risk", + "disease.id": "Orphanet_70595", + "disease.name": "Sensory ataxic neuropathy - dysarthria - ophthalmoparesis", + "diseaseFromSource": "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "literature": [ + "11431686", + "11571332", + "12565911", + "14694057", + "15122711", + "15477547", + "15824347", + "16130100", + "16177225", + "17426723", + "19251978", + "21276947", + "26942291", + "26942292", + "632821" + ], + "studyId": "RCV000014441", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "alleleOrigins": [ + "germline" + ], + "allelicRequirements": [ + "Autosomal recessive inheritance" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Cerebellar ataxia infantile with progressive external ophthalmoplegia", + "Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1", + "Progressive external ophthalmoplegia, autosomal recessive 1" + ], + "confidence": "criteria provided, multiple submitters, no conflicts", + "directionOnTrait": "risk", + "disease.id": "MONDO_0018002", + "disease.name": "adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy", + "diseaseFromSource": "Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "literature": [ + "11431686", + "11571332", + "12565911", + "14694057", + "15122711", + "15477547", + "15824347", + "16130100", + "16177225", + "17426723", + "19251978", + "21276947", + "26942291", + "26942292", + "632821" + ], + "studyId": "RCV000014440", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "alleleOrigins": [ + "germline" + ], + "allelicRequirements": [ + "Autosomal recessive inheritance" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Cerebellar ataxia infantile with progressive external 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"Poliodystrophia cerebri progressiva", + "Progressive cerebral poliodystrophy", + "Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1", + "Progressive external ophthalmoplegia, autosomal recessive 1", + "Progressive sclerosing poliodystrophy", + "SENSORY ATAXIC NEUROPATHY WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE", + "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome" + ], + "confidence": "criteria provided, single submitter", + "directionOnTrait": "risk", + "disease.id": "MONDO_0017575", + "disease.name": "mitochondrial neurogastrointestinal encephalomyopathy", + "diseaseFromSource": "Mitochondrial DNA depletion syndrome 4b", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "studyId": "RCV001813983", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Cerebellar ataxia infantile with progressive external ophthalmoplegia", + "Diffuse cerebral degeneration in infancy", + "Epilepsy, progressive myoclonic, type 5", + "Infantile poliodystrophy", + "MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOPATHY SYNDROME, TYMP-RELATED", + "MNGIE, POLG-RELATED", + "MNGIE, TYMP-RELATED", + "Mitochondrial DNA Depletion Syndrome 4A", + "Mitochondrial DNA Depletion Syndrome, MNGIE Form", + "Mitochondrial DNA depletion syndrome 1", + "Mitochondrial DNA depletion syndrome 1 (MNGIE type)", + "Mitochondrial DNA depletion syndrome 4A (Alpers type)", + "Mitochondrial DNA depletion syndrome 4B, MNGIE type", + "Mitochondrial DNA depletion syndrome 4b", + "Mitochondrial Neurogastrointestinal Encephalopathy Disease, 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"directionOnTrait": "risk", + "disease.id": "MONDO_0017575", + "disease.name": "mitochondrial neurogastrointestinal encephalomyopathy", + "diseaseFromSource": "Mitochondrial DNA depletion syndrome 4b", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "studyId": "RCV000515354", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Cerebellar ataxia infantile with progressive external ophthalmoplegia", + "Diffuse cerebral degeneration in infancy", + "Epilepsy, progressive myoclonic, type 5", + "Infantile poliodystrophy", + "MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOPATHY SYNDROME, TYMP-RELATED", + "MNGIE, POLG-RELATED", + "MNGIE, 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"Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Cerebellar ataxia infantile with progressive external ophthalmoplegia", + "Diffuse cerebral degeneration in infancy", + "Epilepsy, progressive myoclonic, type 5", + "Infantile poliodystrophy", + "MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOPATHY SYNDROME, TYMP-RELATED", + "MNGIE, POLG-RELATED", + "MNGIE, TYMP-RELATED", + "Mitochondrial DNA Depletion Syndrome 4A", + "Mitochondrial DNA Depletion Syndrome, MNGIE Form", + "Mitochondrial DNA depletion syndrome 1", + "Mitochondrial DNA depletion syndrome 1 (MNGIE type)", + "Mitochondrial DNA depletion syndrome 4A (Alpers type)", + "Mitochondrial DNA depletion syndrome 4B, MNGIE type", + "Mitochondrial DNA depletion syndrome 4b", + "Mitochondrial Neurogastrointestinal Encephalopathy Disease, POLG-Related", + "Mitochondrial 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"disease.id": "MONDO_0008758", + "disease.name": "mitochondrial DNA depletion syndrome 4a", + "diseaseFromSource": "Progressive sclerosing poliodystrophy", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "studyId": "RCV000515354", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Cerebellar ataxia infantile with progressive external ophthalmoplegia", + "Diffuse cerebral degeneration in infancy", + "Epilepsy, progressive myoclonic, type 5", + "Infantile poliodystrophy", + "MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOPATHY SYNDROME, TYMP-RELATED", + "MNGIE, POLG-RELATED", + "MNGIE, TYMP-RELATED", + "Mitochondrial DNA Depletion Syndrome 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"Progressive external ophthalmoplegia, autosomal recessive 1", + "Progressive sclerosing poliodystrophy", + "SENSORY ATAXIC NEUROPATHY WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE", + "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome" + ], + "confidence": "criteria provided, single submitter", + "directionOnTrait": "risk", + "disease.id": "Orphanet_726", + "disease.name": "Alpers syndrome", + "diseaseFromSource": "Progressive sclerosing poliodystrophy", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "studyId": "RCV000515354", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "alleleOrigins": [ + "germline" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive 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RECESSIVE", + "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome" + ], + "confidence": "criteria provided, single submitter", + "directionOnTrait": "risk", + "disease.id": "Orphanet_726", + "disease.name": "Alpers syndrome", + "diseaseFromSource": "Progressive sclerosing poliodystrophy", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "studyId": "RCV001813983", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "alleleOrigins": [ + "germline" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Cerebellar ataxia infantile with progressive external ophthalmoplegia", + "Diffuse cerebral degeneration in 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+ "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome" + ], + "confidence": "criteria provided, single submitter", + "directionOnTrait": "risk", + "disease.id": "MONDO_0008003", + "disease.name": "autosomal dominant progressive external ophthalmoplegia", + "diseaseFromSource": "Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "studyId": "RCV001731286", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Cerebellar ataxia infantile with progressive external ophthalmoplegia", 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"15_89327201_C_T" + }, + { + "alleleOrigins": [ + "germline" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Familial spastic paraparesis", + "Hereditary spastic paraplegia" + ], + "confidence": "criteria provided, single submitter", + "directionOnTrait": "risk", + "disease.id": "MONDO_0019064", + "disease.name": "hereditary spastic paraplegia", + "diseaseFromSource": "Hereditary spastic paraplegia", + "diseaseId": "EFO_0000508", + "diseaseName": "genetic disorder", + "studyId": "RCV001847600", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "alleleOrigins": [ + "germline" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Cerebellar ataxia 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matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Cerebellar ataxia infantile with progressive external ophthalmoplegia", + "Diffuse cerebral degeneration in infancy", + "Epilepsy, progressive myoclonic, type 5", + "Infantile poliodystrophy", + "MNGIE, POLG-RELATED", + "Mitochondrial DNA Depletion Syndrome 4A", + "Mitochondrial DNA depletion syndrome 4A (Alpers type)", + "Mitochondrial DNA depletion syndrome 4B, MNGIE type", + "Mitochondrial DNA depletion syndrome 4b", + "Mitochondrial Neurogastrointestinal Encephalopathy Disease, POLG-Related", + "Neuronal degeneration of childhood with liver disease, progressive", + "PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA, AUTOSOMAL DOMINANT 1", + "Poliodystrophia cerebri progressiva", + "Progressive cerebral poliodystrophy", + "Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1", + "Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1", + "Progressive external ophthalmoplegia, autosomal recessive 1", + "Progressive sclerosing poliodystrophy", + "SENSORY ATAXIC NEUROPATHY WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE", + "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome" + ], + "confidence": "criteria provided, single submitter", + "directionOnTrait": "risk", + "disease.id": "MONDO_0017575", + "disease.name": "mitochondrial neurogastrointestinal encephalomyopathy", + "diseaseFromSource": "Mitochondrial DNA depletion syndrome 4b", + "diseaseId": "MONDO_0044970", + "diseaseName": "mitochondrial disease", + "studyId": "RCV001731286", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "alleleOrigins": [ + "germline" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Cerebellar ataxia infantile with progressive external ophthalmoplegia", + "Diffuse cerebral degeneration in infancy", + "Epilepsy, progressive myoclonic, type 5", + "Infantile poliodystrophy", + "MNGIE, POLG-RELATED", + "Mitochondrial DNA Depletion Syndrome 4A", + "Mitochondrial DNA depletion syndrome 4A (Alpers type)", + "Mitochondrial DNA depletion syndrome 4B, MNGIE type", + "Mitochondrial DNA depletion syndrome 4b", + "Mitochondrial Neurogastrointestinal Encephalopathy Disease, POLG-Related", + "Neuronal degeneration of childhood with liver disease, progressive", + "Poliodystrophia cerebri progressiva", + "Progressive cerebral poliodystrophy", + "Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1", + "Progressive external ophthalmoplegia, autosomal recessive 1", + "Progressive sclerosing poliodystrophy", + "SENSORY ATAXIC NEUROPATHY WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE", + "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome" + ], + "confidence": "criteria provided, single submitter", + "directionOnTrait": "risk", + "disease.id": "MONDO_0011835", + "disease.name": "sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "diseaseFromSource": "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "diseaseId": "MONDO_0044970", + "diseaseName": "mitochondrial disease", + "studyId": "RCV001813983", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + }, + { + "alleleOrigins": [ + "germline" + ], + "approvedSymbol": "POLG", + "clinicalSignificances": [ + "pathogenic" + ], + "cohortPhenotypes": [ + "Alpers Syndrome", + "Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis", + "Alpers disease", + "Alpers progressive infantile poliodystrophy", + "Alpers-Huttenlocher Syndrome", + "Cerebellar ataxia infantile with progressive external ophthalmoplegia", + "Diffuse cerebral degeneration in infancy", + "Epilepsy, progressive myoclonic, type 5", + "Infantile poliodystrophy", + "MNGIE, POLG-RELATED", + "Mitochondrial DNA Depletion Syndrome 4A", + "Mitochondrial DNA depletion syndrome 4A (Alpers type)", + "Mitochondrial DNA depletion syndrome 4B, MNGIE type", + "Mitochondrial DNA depletion syndrome 4b", + "Mitochondrial Neurogastrointestinal Encephalopathy Disease, POLG-Related", + "Neuronal degeneration of childhood with liver disease, progressive", + "Poliodystrophia cerebri progressiva", + "Progressive cerebral poliodystrophy", + "Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1", + "Progressive external ophthalmoplegia, autosomal recessive 1", + "Progressive sclerosing poliodystrophy", + "SENSORY ATAXIC NEUROPATHY WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE", + "Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis", + "Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome" + ], + "confidence": "criteria provided, single submitter", + "directionOnTrait": "risk", + "disease.id": "MONDO_0008758", + "disease.name": "mitochondrial DNA depletion syndrome 4a", + "diseaseFromSource": "Progressive sclerosing poliodystrophy", + "diseaseId": "MONDO_0044970", + "diseaseName": "mitochondrial disease", + "studyId": "RCV001813983", + "targetId": "ENSG00000140521", + "variantId": "15_89327201_C_T" + } + ] + } +}`), + }; +} \ No newline at end of file diff --git a/packages/sections/src/variant/EVA/Description.tsx b/packages/sections/src/variant/EVA/Description.tsx new file mode 100644 index 000000000..be03b02b6 --- /dev/null +++ b/packages/sections/src/variant/EVA/Description.tsx @@ -0,0 +1,18 @@ +import { Link } from "ui"; + +type DescriptionProps = { + variantId: string; +}; + +function Description({ variantId }: DescriptionProps) { + return ( + <> + Genetic variation from clinical submissions associating {variantId} to a disease/phenotype. Source:{" "} + + EVA + + + ); +} + +export default Description; diff --git a/packages/sections/src/variant/EVA/Summary.tsx b/packages/sections/src/variant/EVA/Summary.tsx new file mode 100644 index 000000000..437471d25 --- /dev/null +++ b/packages/sections/src/variant/EVA/Summary.tsx @@ -0,0 +1,42 @@ +import { SummaryItem, usePlatformApi } from "ui"; + +import { definition } from "."; +import { dataTypesMap } from "../../dataTypes"; +// import EVA_SUMMARY from "./EVASummaryQuery.gql"; + +function Summary() { + + // !! THIS IS UGLY BUT AVOIDS ADDING TYPES IN dataType FILE FOR NOW + type dataTypesMapType = { + [index: string]: number; + }; + const dataTypesMapTyped = dataTypesMap as dataTypesMapType; + + // !! USE PLACEHOLDER REQUEST FOR NOW !! + // const request = usePlatformApi(EVA_SUMMARY); + const request = { + loading: false, + error: undefined, + data: true, // data is not actually used by summary - only cares if there is data + }; + + return ( + {}} // !! renderSummary PROP NOT USED ANYMORE ANYWAY? + // renderSummary={({ evaSummary }) => { + // const { count } = evaSummary; + // return `${count} ${count === 1 ? "entry" : "entries"}`; + // }} + subText={dataTypesMapTyped.genetic_association} + /> + ); +} + +// !!!!!!!!!!! +// Summary.fragments = { +// evaSummary: EVA_SUMMARY, +// }; + +export default Summary; \ No newline at end of file diff --git a/packages/sections/src/variant/EVA/index.ts b/packages/sections/src/variant/EVA/index.ts new file mode 100644 index 000000000..2e223cb27 --- /dev/null +++ b/packages/sections/src/variant/EVA/index.ts @@ -0,0 +1,16 @@ + +// !!!!!!!!!! +// ADD POSSIBILITY FOR PRIVATE SECTIONS IN PARTNER PAGE +// !!!!!!!!!! +// import { isPrivateVariantSection } from "../../utils/partnerPreviewUtils"; + +// !! NEED TO TYPE WHATEVER PASSED INTO HASDATA - SEE SUMMARY +const id = "eva"; +export const definition = { + id, + name: "ClinVar", + shortName: "CV", + hasData: () => true, // !! CHANGE WHEN USE GQL !! + // hasData: ({ eva }) => eva.count > 0, + isPrivate: false, // isPrivateVariantSection(id), +}; diff --git a/packages/sections/src/variant/InSilicoPredictors/Body.tsx b/packages/sections/src/variant/InSilicoPredictors/Body.tsx new file mode 100644 index 000000000..a618f622a --- /dev/null +++ b/packages/sections/src/variant/InSilicoPredictors/Body.tsx @@ -0,0 +1,135 @@ +// import { useQuery } from "@apollo/client"; +import { Typography } from "@mui/material"; +import { Link, SectionItem, Tooltip, PublicationsDrawer, DataTable } from "ui"; +import { definition } from "../InSilicoPredictors"; +import Description from "../InSilicoPredictors/Description"; +import { epmcUrl } from "../../utils/urls"; +import { identifiersOrgLink } from "../../utils/global"; +import { defaultRowsPerPageOptions, naLabel, sectionsBaseSizeQuery, +} from "../../constants"; +// import UNIPROT_VARIANTS_QUERY from "./UniprotVariantsQuery.gql"; + +function getColumns(label: string) { + return [ + { + id: "method", + label: "Method", + }, + { + id: "assessment", + label: "Prediction", + renderCell: ({ assessment, flag }) => ( + flag + ? ( + + + Flag: {flag} + + + } + showHelpIcon + > + {assessment ?? naLabel} + + ) : ( + assessment ?? naLabel + ) + ) + }, + { + id: "score", + label: "Score", + }, + ]; +} + +type BodyProps = { + id: string, + label: string, + entity: string, +}; + + +export function Body({ id, label, entity }) { + + // const variables = { + // ensemblId: ensgId, + // efoId, + // size: sectionsBaseSizeQuery, + // }; + + const columns = getColumns(label); + + // const request = useQuery(UNIPROT_VARIANTS_QUERY, { + // variables, + // }); + const request = mockQuery(); + + return ( + } + renderBody={() => { + // const rows = request.data.variant.inSilicoPredictors; + const rows = + [...request.data.variant.inSilicoPredictors].sort((row1, row2) => { + return row1.method.localeCompare(row2.method); + }); + return ( + + ); + }} + /> + ); +} + +export default Body; + +function mockQuery() { + return { + loading: false, + error: undefined, + data: JSON.parse(` +{ + "variant": { + "inSilicoPredictors": [ + { + "method": "alphaMissense", + "score": 0.077, + "assessment": "likely_benign" + }, + { + "method": "phred scaled CADD", + "score": 7.293 + }, + { + "method": "sift max", + "score": 0.2, + "assessment": "MODERATE" + }, + { + "method": "polyphen max", + "score": 0.069, + "assessment": "tolerated" + }, + { + "method": "loftee", + "assessment": "high-confidence LoF variant", + "flag": "PHYLOCSF_WEAK" + } + ] + } +}`), + }; +} diff --git a/packages/sections/src/variant/InSilicoPredictors/Description.tsx b/packages/sections/src/variant/InSilicoPredictors/Description.tsx new file mode 100644 index 000000000..7125d6ea3 --- /dev/null +++ b/packages/sections/src/variant/InSilicoPredictors/Description.tsx @@ -0,0 +1,18 @@ +import { Link } from "ui"; + +type DescriptionProps = { + variantId: string; +}; + +function Description({ variantId }: DescriptionProps) { + return ( + <> + Predicted functional effect of {variantId}. {" "}Source:{" "} + + VEP + + + ); +} + +export default Description; \ No newline at end of file diff --git a/packages/sections/src/variant/InSilicoPredictors/Summary.tsx b/packages/sections/src/variant/InSilicoPredictors/Summary.tsx new file mode 100644 index 000000000..fd8d58567 --- /dev/null +++ b/packages/sections/src/variant/InSilicoPredictors/Summary.tsx @@ -0,0 +1,42 @@ +import { SummaryItem, usePlatformApi } from "ui"; + +import { definition } from "."; +import { dataTypesMap } from "../../dataTypes"; +// import UNIPROT_VARIANTS_SUMMARY from "./UniprotVariantsSummaryQuery.gql"; + +function Summary() { + + // !! THIS IS UGLY BUT AVOIDS ADDING TYPES IN dataType FILE FOR NOW + type dataTypesMapType = { + [index: string]: number; + }; + const dataTypesMapTyped = dataTypesMap as dataTypesMapType; + + // !! USE PLACEHOLDER REQUEST FOR NOW !! + // const request = usePlatformApi(UNIPROT_VARIANTS_SUMMARY); + const request = { + loading: false, + error: undefined, + data: true, // data is not actually used by summary - only cares if there is data + }; + + return ( + {}} // !! renderSummary PROP NOT USED ANYMORE ANYWAY? + // renderSummary={({ uniprotVariantsSummary }) => { + // const { count } = uniprotVariantsSummary; + // return `${count} ${count === 1 ? "entry" : "entries"}`; + // }} + subText={dataTypesMapTyped.genetic_association} // !! LEAVE AS GENETIC ASSOCITION FOR NOW + /> + ); +} + +// !!!!!!!!!!!!! +// Summary.fragments = { +// UniprotVariantsSummary: UNIPROT_VARIANTS_SUMMARY, +// }; + +export default Summary; diff --git a/packages/sections/src/variant/InSilicoPredictors/index.ts b/packages/sections/src/variant/InSilicoPredictors/index.ts new file mode 100644 index 000000000..2b681c2fd --- /dev/null +++ b/packages/sections/src/variant/InSilicoPredictors/index.ts @@ -0,0 +1,11 @@ +// import { isPrivateEvidenceSection } from "../../utils/partnerPreviewUtils"; + +const id = "in_silico_predictors"; +export const definition = { + id, + name: "In silico predictors", + shortName: "VP", + // UPDATE HERE ONCE HAVE PROPER DATA + hasData: data => true, // data.uniprotVariantsSummary.count > 0, + isPrivate: false, // isPrivateEvidenceSection(id), +}; diff --git a/packages/sections/src/variant/UniProtVariants/Body.tsx b/packages/sections/src/variant/UniProtVariants/Body.tsx new file mode 100644 index 000000000..103e99baf --- /dev/null +++ b/packages/sections/src/variant/UniProtVariants/Body.tsx @@ -0,0 +1,289 @@ +// import { useQuery } from "@apollo/client"; +import { Typography } from "@mui/material"; +import { Link, SectionItem, Tooltip, PublicationsDrawer, DataTable } from "ui"; +import { definition } from "../../variant/UniProtVariants"; +import Description from "../../variant/UniProtVariants/Description"; +import { epmcUrl } from "../../utils/urls"; +import { identifiersOrgLink } from "../../utils/global"; +import { defaultRowsPerPageOptions, sectionsBaseSizeQuery, +} from "../../constants"; +// import UNIPROT_VARIANTS_QUERY from "./UniprotVariantsQuery.gql"; + +function getColumns(label: string) { + return [ + { + id: "targetFromSourceId", + label: "Reported protein", + renderCell: ({ targetFromSourceId }) => ( + + {targetFromSourceId} + + ), + }, + { + id: "disease.name", + label: "Disease/phenotype", + renderCell: ({ + "disease.id": disease_id, + "disease.name": disease_name, + diseaseFromSource + }) => ( + + + Reported disease or phenotype: + + + {diseaseFromSource} + + + } + showHelpIcon + > + {disease_name} + + ), + }, + { + id: "confidence", + label: "Confidence", + }, + { + label: "Literature", + renderCell: ({ literature }) => { + const literatureList = + literature?.reduce((acc, id) => { + if (id !== "NA") { + acc.push({ + name: id, + url: epmcUrl(id), + group: "literature", + }); + } + return acc; + }, []) || []; + + return ( + + ); + }, + }, + ]; +} + +type BodyProps = { + id: string, + label: string, + entity: string, +}; + + +export function Body({ id, label, entity }) { + + // ID IS JUST THE VARIANT ID STRING FOR NOW + // const { ensgId, efoId } = id; + + // const variables = { + // ensemblId: ensgId, + // efoId, + // size: sectionsBaseSizeQuery, + // }; + + const columns = getColumns(label); + + // const request = useQuery(UNIPROT_VARIANTS_QUERY, { + // variables, + // }); + const request = mockQuery(); + + return ( + } + renderBody={({ disease }) => { + // const { rows } = disease.uniprotVariantsSummary; + const rows = request.data.variant.uniProtVariants; + return ( + + ); + }} + /> + ); +} + +export default Body; + +function mockQuery() { + return { + loading: false, + error: undefined, + data: JSON.parse(` +{ + "variant": { + "uniProtVariants": [ + { + "variantId": "15_89327201_C_T", + "confidence": "high", + "diseaseFromSource": "Mitochondrial DNA depletion syndrome 4A", + "literature": [ + "16639411", + "15917273", + "15477547", + "14635118", + "15824347", + "11431686", + "15122711", + "26942291", + "12565911", + "18828154", + "14694057", + "15689359", + "12707443" + ], + "targetFromSourceId": "P54098", + "target.id": "ENSG00000140521", + "target.approvedSymbol": "POLG", + "disease.id": "Orphanet_726", + "disease.name": "Alpers syndrome" + }, + { + "variantId": "15_89327201_C_T", + "confidence": "high", + "diseaseFromSource": "Mitochondrial DNA depletion syndrome 4A", + "literature": [ + "16639411", + "15917273", + "15477547", + "14635118", + "15824347", + "11431686", + "15122711", + "26942291", + "12565911", + "18828154", + "14694057", + "15689359", + "12707443" + ], + "targetFromSourceId": "P54098", + "target.id": "ENSG00000140521", + "target.approvedSymbol": "POLG", + "disease.id": "MONDO_0008758", + "disease.name": "mitochondrial DNA depletion syndrome 4a" + }, + { + "variantId": "15_89327201_C_T", + "confidence": "high", + "diseaseFromSource": "Sensory ataxic neuropathy dysarthria and ophthalmoparesis", + "literature": [ + "16639411", + "15917273", + "15477547", + "14635118", + "15824347", + "11431686", + "15122711", + "26942291", + "12565911", + "18828154", + "14694057", + "15689359", + "12707443" + ], + "targetFromSourceId": "P54098", + "target.id": "ENSG00000140521", + "target.approvedSymbol": "POLG", + "disease.id": "MONDO_0011835", + "disease.name": "sensory ataxic neuropathy, dysarthria, and ophthalmoparesis" + }, + { + "variantId": "15_89327201_C_T", + "confidence": "high", + "diseaseFromSource": "Spinocerebellar ataxia with epilepsy", + "literature": [ + "16639411", + "15917273", + "15477547", + "14635118", + "15824347", + "11431686", + "15122711", + "26942291", + "12565911", + "18828154", + "14694057", + "15689359", + "12707443" + ], + "targetFromSourceId": "P54098", + "target.id": "ENSG00000140521", + "target.approvedSymbol": "POLG", + "disease.id": "Orphanet_70595", + "disease.name": "Sensory ataxic neuropathy - dysarthria - ophthalmoparesis" + }, + { + "variantId": "15_89327201_C_T", + "confidence": "high", + "diseaseFromSource": "Sensory ataxic neuropathy dysarthria and ophthalmoparesis", + "literature": [ + "16639411", + "15917273", + "15477547", + "14635118", + "15824347", + "11431686", + "15122711", + "26942291", + "12565911", + "18828154", + "14694057", + "15689359", + "12707443" + ], + "targetFromSourceId": "P54098", + "target.id": "ENSG00000140521", + "target.approvedSymbol": "POLG", + "disease.id": "Orphanet_70595", + "disease.name": "Sensory ataxic neuropathy - dysarthria - ophthalmoparesis" + }, + { + "variantId": "15_89327201_C_T", + "confidence": "high", + "diseaseFromSource": "Spinocerebellar ataxia with epilepsy", + "literature": [ + "16639411", + "15917273", + "15477547", + "14635118", + "15824347", + "11431686", + "15122711", + "26942291", + "12565911", + "18828154", + "14694057", + "15689359", + "12707443" + ], + "targetFromSourceId": "P54098", + "target.id": "ENSG00000140521", + "target.approvedSymbol": "POLG", + "disease.id": "MONDO_0011835", + "disease.name": "sensory ataxic neuropathy, dysarthria, and ophthalmoparesis" + } + ] + } +}`), + }; +} diff --git a/packages/sections/src/variant/UniProtVariants/Description.tsx b/packages/sections/src/variant/UniProtVariants/Description.tsx new file mode 100644 index 000000000..5f5ecf471 --- /dev/null +++ b/packages/sections/src/variant/UniProtVariants/Description.tsx @@ -0,0 +1,18 @@ +import { Link } from "ui"; + +type DescriptionProps = { + variantId: string; +}; + +function Description({ variantId }: DescriptionProps) { + return ( + <> + Literature-based curation associating {variantId}{" "} to a disease/phenotype. Source:{" "} + + UniProt + + + ); +} + +export default Description; \ No newline at end of file diff --git a/packages/sections/src/variant/UniProtVariants/Summary.tsx b/packages/sections/src/variant/UniProtVariants/Summary.tsx new file mode 100644 index 000000000..ba8a8ed22 --- /dev/null +++ b/packages/sections/src/variant/UniProtVariants/Summary.tsx @@ -0,0 +1,42 @@ +import { SummaryItem, usePlatformApi } from "ui"; + +import { definition } from "."; +import { dataTypesMap } from "../../dataTypes"; +// import UNIPROT_VARIANTS_SUMMARY from "./UniprotVariantsSummaryQuery.gql"; + +function Summary() { + + // !! THIS IS UGLY BUT AVOIDS ADDING TYPES IN dataType FILE FOR NOW + type dataTypesMapType = { + [index: string]: number; + }; + const dataTypesMapTyped = dataTypesMap as dataTypesMapType; + + // !! USE PLACEHOLDER REQUEST FOR NOW !! + // const request = usePlatformApi(UNIPROT_VARIANTS_SUMMARY); + const request = { + loading: false, + error: undefined, + data: true, // data is not actually used by summary - only cares if there is data + }; + + return ( + {}} // !! renderSummary PROP NOT USED ANYMORE ANYWAY? + // renderSummary={({ uniprotVariantsSummary }) => { + // const { count } = uniprotVariantsSummary; + // return `${count} ${count === 1 ? "entry" : "entries"}`; + // }} + subText={dataTypesMapTyped.genetic_association} + /> + ); +} + +// !!!!!!!!!!!!! +// Summary.fragments = { +// UniprotVariantsSummary: UNIPROT_VARIANTS_SUMMARY, +// }; + +export default Summary; diff --git a/packages/sections/src/variant/UniProtVariants/index.ts b/packages/sections/src/variant/UniProtVariants/index.ts new file mode 100644 index 000000000..a653651b0 --- /dev/null +++ b/packages/sections/src/variant/UniProtVariants/index.ts @@ -0,0 +1,11 @@ +// import { isPrivateEvidenceSection } from "../../utils/partnerPreviewUtils"; + +const id = "uniprot_variants"; +export const definition = { + id, + name: "UniProt variants", + shortName: "UV", + // !! UPDATE HERE ONCE HAVE PROPER DATA + hasData: data => true, // data.uniprotVariantsSummary.count > 0, + isPrivate: false, // isPrivateEvidenceSection(id), +}; From 2ccf3a6c601a76aace8c25344c5651d32ccec0b3 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Mon, 10 Jun 2024 17:17:48 +0100 Subject: [PATCH 03/17] draft pharmacokinetics widget (#383) --- .../src/pages/VariantPage/Profile.tsx | 9 +- apps/platform/src/pages/VariantPage/types.ts | 23 +- .../src/variant/Pharmacogenomics/Body.tsx | 4823 +++++++++++++++++ .../variant/Pharmacogenomics/Description.tsx | 19 + .../PharmacogenomicsTable.tsx | 200 + .../src/variant/Pharmacogenomics/Summary.tsx | 33 + .../src/variant/Pharmacogenomics/index.ts | 7 + 7 files changed, 5111 insertions(+), 3 deletions(-) create mode 100644 packages/sections/src/variant/Pharmacogenomics/Body.tsx create mode 100644 packages/sections/src/variant/Pharmacogenomics/Description.tsx create mode 100644 packages/sections/src/variant/Pharmacogenomics/PharmacogenomicsTable.tsx create mode 100644 packages/sections/src/variant/Pharmacogenomics/Summary.tsx create mode 100644 packages/sections/src/variant/Pharmacogenomics/index.ts diff --git a/apps/platform/src/pages/VariantPage/Profile.tsx b/apps/platform/src/pages/VariantPage/Profile.tsx index d8707401b..b362393dd 100644 --- a/apps/platform/src/pages/VariantPage/Profile.tsx +++ b/apps/platform/src/pages/VariantPage/Profile.tsx @@ -9,17 +9,20 @@ import { import InSilicoPredictorsSummary from "sections/src/variant/InSilicoPredictors/Summary"; import EVASummary from "sections/src/variant/EVA/Summary"; import UniProtVariantsSummary from "sections/src/variant/UniProtVariants/Summary"; +import PharmacogenomicsSummary from "sections/src/variant/Pharmacogenomics/Summary"; import ProfileHeader from "./ProfileHeader"; const InSilicoPredictorsSection = lazy(() => import("sections/src/variant/InSilicoPredictors/Body")); const EVASection = lazy(() => import("sections/src/variant/EVA/Body")); const UniProtVariantsSection = lazy(() => import("sections/src/variant/UniProtVariants/Body")); +const PharmacogenomicsSection = lazy(() => import("sections/src/variant/Pharmacogenomics/Body")); const summaries = [ InSilicoPredictorsSummary, EVASummary, - UniProtVariantsSummary + UniProtVariantsSummary, + PharmacogenomicsSummary, ]; const VARIANT = "variant"; @@ -48,6 +51,7 @@ function Profile({ varId }: ProfileProps) { + @@ -60,6 +64,9 @@ function Profile({ varId }: ProfileProps) { }> + }> + + {/* NEED ANYTHING IN ???? see evidence page */} diff --git a/apps/platform/src/pages/VariantPage/types.ts b/apps/platform/src/pages/VariantPage/types.ts index 3e3de5f40..9c3975e2a 100644 --- a/apps/platform/src/pages/VariantPage/types.ts +++ b/apps/platform/src/pages/VariantPage/types.ts @@ -84,7 +84,7 @@ export type ClinVarType = { // UniProtVariants // =============== -export type UniProtVariants = { +export type UniProtVariantsType = { variantId: string, confidence: string, diseaseFromSource: string, @@ -94,4 +94,23 @@ export type UniProtVariants = { "target.approvedSymbol": string, "disease.id": string, "disease.name": string, -}; +}; + +// ================ +// Pharmacogenomics +// ================ + +export type PharmacogenomicsType = { + genotypeId: string, + isDirectTarget: boolean, + drugFromSource: string, + drugId: string, + phenotypeFromSourceId: string | null, + genotypeAnnotationText: string, + phenotypeText: string, + pgxCategory: string, + evidenceLevel: string, + datasourceId: string, + studyId: string, + literature: string[], +}; diff --git a/packages/sections/src/variant/Pharmacogenomics/Body.tsx b/packages/sections/src/variant/Pharmacogenomics/Body.tsx new file mode 100644 index 000000000..fa8520945 --- /dev/null +++ b/packages/sections/src/variant/Pharmacogenomics/Body.tsx @@ -0,0 +1,4823 @@ +// import { useQuery } from "@apollo/client"; +import { SectionItem } from "ui"; +import { definition } from "."; +import Description from "./Description"; +import PharmacogenomicsTable from "./PharmacogenomicsTable"; + +// import PHARMACOGENOMICS_QUERY from "./Pharmacogenomics.gql"; + +type BodyProps = { + id: string, + label: string, + entity: string, +}; + +function Body({ id, label, entity }: BodyProps) { + + // !!!! LOAD LOCAL DATA FOR NOW + // const variables = { ensemblId }; + // const request = useQuery(PHARMACOGENOMICS_QUERY, { + // variables, + // }); + const request = mockQuery(); + + return ( + } + renderBody={({ variant }) => ( + + )} + /> + ); +} + +export default Body; + +// !! HARDCODE DATA FOR NOW !! +function mockQuery() { + return { + loading: false, + error: undefined, + data: JSON.parse(` +{ + "variant": { + "pharmacogenomics": [ + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "fluvastatin", + "drugId": "CHEMBL2220442", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have decreased concentrations of fluvastatin as compared to patients with the CC or CT genotypes. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect fluvastatin concentrations. This annotation only covers the pharmacokinetic relationship between rs4149056 and fluvastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "decreased concentrations of fluvastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244700", + "literature": [ + "17015053", + "30989645" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "lovastatin", + "drugId": "CHEMBL503", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "TPatients with the rs4149056 CT genotype may have an increased risk of lovastatin-related myopathy when treated with lovastatin as compared to patients with the TT genotype. Other genetic and clinical factors may also influence risk of toxicity to lovastatin.", + "phenotypeText": "increased risk of lovastatin-related myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451465324", + "literature": [ + "34114646" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "lopinavir", + "drugId": "CHEMBL729", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with HIV and the TT genotype may have decreased plasma levels of lopinavir as compared to patients with the CC genotype. However, one study failed to find this association. Other genetic and clinical factors may also influence lopinavir concentrations in a patients. This annotation only covers the pharmacokinetic relationship between rs4149056 and lopinavir and does not include evidence about clinical outcomes.", + "phenotypeText": "decreased plasma levels of lopinavir", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444704359", + "literature": [ + "20051929", + "20078617", + "21743379", + "23503447", + "32022294", + "27142945", + "28718515" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "amprenavir", + "drugId": "CHEMBL116", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with HIV infections and the CT genotype may have decreased trough concentrations of amprenavir as compared to patients with the TT genotype. Note that this association was only found in patients of European descent, and not in African American or Hispanic patients. Other genetic and clinical factors may also affect concentrations of amprenavir in patients.", + "phenotypeText": "decreased trough concentrations of amprenavir", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451116100", + "literature": [ + "23503447" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "atorvastatin", + "drugId": "CHEMBL1487", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have increased plasma concentration of atorvastatin when treated concomitantly with rifampin as compared to patients with the CC or CT genotypes. Other genetic and clinical factors may also influence a patient's metabolism and response to atorvastatin.", + "phenotypeText": "increased plasma concentration of atorvastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981345311", + "literature": [ + "19374892" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "lovastatin acid", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have decreased concentration of lovastatin acid as compared to patients with the CC or CT genotype. Other genetic and clinical factors may also influence the metabolism of lovastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and lovastatin acid or lovastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "decreased concentration of lovastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451678112", + "literature": [ + "27967318", + "26020121" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "lovastatin acid", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have increased concentrations of lovastatin acid as compared to patients with the TT genotype. Other genetic and clinical factors may also affect metabolism of lovastatin acid. This annotation only covers the pharmacokinetic relationship between rs4149056 and lovastatin acid and does not include evidence about clinical outcomes.", + "phenotypeText": "increased concentrations of lovastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451244680", + "literature": [ + "27967318" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "methotrexate", + "drugId": "CHEMBL34259", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with precursor cell lymphoblastic leukemia-lymphoma and the rs4149056 CT genotype may have an increased response to methotrexate as compared to patients with the CC genotype. However, conflicting evidence has been reported. Other clinical and genetic factors may also influence response to methotrexate.", + "phenotypeText": "increased response", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449004841", + "literature": [ + "24386571", + "28525903" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "cytarabine", + "drugId": "CHEMBL803", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype and an increased likelihood of toxic liver disease as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "decreased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "ticagrelor", + "drugId": "CHEMBL398435", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype and acute coronary syndrome may have increased concentrations of ticagrelor compared to patients with the CT and TT genotypes. Other factors may affect concentrations of ticagrelor.", + "phenotypeText": "increased concentrations of ticagrelor", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448100347", + "literature": [ + "25935875" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "atorvastatin", + "drugId": "CHEMBL1487", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have an increased risk of myopathy when treated with atorvastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of developing myopathy when treated with atorvastatin.", + "phenotypeText": "increased risk of myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1043880818", + "literature": [ + "32453264", + "32128760", + "30595243", + "28812116", + "26376374", + "30569848", + "34114646", + "33608664", + "33150478", + "21928084", + "21243006", + "23942138", + "24263182", + "26086347", + "27839692", + "28940218", + "19833260" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "atorvastatin", + "drugId": "CHEMBL1487", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have an increased risk of myopathy when treated with atorvastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of developing myopathy when treated with atorvastatin.", + "phenotypeText": "increased risk of myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1043880818", + "literature": [ + "32453264", + "32128760", + "30595243", + "28812116", + "26376374", + "30569848", + "34114646", + "33608664", + "33150478", + "21928084", + "21243006", + "23942138", + "24263182", + "26086347", + "27839692", + "28940218", + "19833260" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "hmg coa reductase inhibitors", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have an increased risk of developing myopathy when treated with statins as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect risk of statin-induced myopathy.", + "phenotypeText": "increased risk of developing myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "981345382", + "literature": [ + "31242253", + "30250148", + "21178985", + "23942138", + "31220337", + "31967516", + "27595674", + "27839692", + "29785580", + "29785580" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "repaglinide", + "drugId": "CHEMBL1272", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have decreased exposure of repaglinide and decreased response to repaglinide as compared to patients with the CC genotype and increased exposure as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a exposure of and response to repaglinide.", + "phenotypeText": "decreased response", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655384645", + "literature": [ + "18187595", + "29748863" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "methotrexate", + "drugId": "CHEMBL34259", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Pediatric patients with the rs4149056 CT genotype and cancers may have decreased clearance of methotrexate as compared to patients with the TT genotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between rs4149056 and methotrexate and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence clearance of methotrexate.", + "phenotypeText": "decreased clearance of methotrexate", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655387949", + "literature": [ + "23233662", + "19901119", + "31870219", + "33501733", + "23652803", + "25098908", + "24712521", + "28525903", + "29791011" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "idarubicin", + "drugId": "CHEMBL1117", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "decreased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "lopinavir", + "drugId": "CHEMBL729", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with HIV and the CT genotype may have decreased plasma levels of lopinavir as compared to patients with the CC genotype, but increased plasma levels as compared to patients with the TT genotype. However, one study failed to find this association. Other genetic and clinical factors may also influence lopinavir concentrations in a patients. This annotation only covers the pharmacokinetic relationship between rs4149056 and lopinavir and does not include evidence about clinical outcomes.", + "phenotypeText": "decreased plasma levels", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444704359", + "literature": [ + "20051929", + "20078617", + "21743379", + "23503447", + "32022294", + "27142945", + "28718515" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "epirubicin", + "drugId": "CHEMBL417", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and hormone insensitive breast cancer may experience increased risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the CT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "fluvastatin", + "drugId": "CHEMBL2220442", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have an increased risk of developing myopathy when treated with fluvastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect a patient's risk of developing fluvastatin-induced myopathy.", + "phenotypeText": "increased risk of developing myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244720", + "literature": [ + "23942138", + "27839692" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype and hormone insensitive breast cancer may experience lower risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the TT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "lower risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "pravastatin", + "drugId": "CHEMBL1144", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype who are treated with pravastatin may have a smaller reduction in LDL and total cholesterol as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence a patient's response to pravastatin treatment.", + "phenotypeText": "smaller reduction in LDL and total cholesterol", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1043880802", + "literature": [ + "25379722", + "22189199", + "15548849", + "17439540", + "16722833", + "16103896", + "21851379", + "16678544", + "18794729", + "18794729", + "16917677" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "pravastatin", + "drugId": "CHEMBL1144", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have increased plasma concentrations of pravastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence a patient's metabolism of pravastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and pravastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased plasma concentrations of pravastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981345293", + "literature": [ + "30549267", + "26744986", + "15226675", + "16722833", + "16722833", + "15116054", + "16678544", + "17015053", + "17622941", + "12811365", + "19776292", + "18408565", + "17047488", + "15970799", + "17622941", + "17622941", + "17622941", + "17622941" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "simvastatin", + "drugId": "CHEMBL1064", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have decreased lipid-lowering response to simvastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. The effect size may be small. Other genetic and clinical factors may also influence response to simvastatin.", + "phenotypeText": "decreased lipid-lowering response", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451356520", + "literature": [ + "30336686", + "29575099", + "25932441", + "28482130", + "28482130", + "20207952", + "24668570", + "23100282", + "24096969", + "22668755", + "23263738", + "25379722" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype and hormone insensitive breast cancer may experience lower risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the TT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "lower risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "doxorubicin", + "drugId": "CHEMBL53463", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype and hormone insensitive breast cancer may experience lower risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the TT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "lower risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "rifampin", + "drugId": "CHEMBL374478", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have decreased plasma concentration of atorvastatin when treated concomitantly with rifampin as compared to patients with the TT genotypes. Other genetic and clinical factors may also influence a patient's metabolism and response to atorvastatin.", + "phenotypeText": "decreased plasma concentration", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981345311", + "literature": [ + "19374892" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "methotrexate", + "drugId": "CHEMBL34259", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Pediatric patients with the rs4149056 CC genotype and cancers may have decreased clearance of methotrexate as compared to patients with the TT genotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between rs4149056 and methotrexate and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence clearance of methotrexate.", + "phenotypeText": "decreased clearance of methotrexate", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655387949", + "literature": [ + "23233662", + "19901119", + "31870219", + "33501733", + "23652803", + "25098908", + "24712521", + "28525903", + "29791011" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "letermovir", + "drugId": "CHEMBL1241951", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have an increased AUC of letermovir as compared to patients with the TT genotype. Other genetic and clinical factors may also affect a patient's exposure to letermovir.", + "phenotypeText": "increased AUC of letermovir", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451105200", + "literature": [ + "31022310" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "simvastatin", + "drugId": "CHEMBL1064", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have increased serum concentrations of simvastatin acid as compared to patients with the TT genotype, but decreased concentrations as compared to patients with the CC genotype. This annotation only covers the pharmacokinetic relationship between rs4149056 and simvastatin acid and does not include evidence about clinical outcomes. Other genetic and clinical factors may also affect serum concentrations of simvastatin acid.", + "phenotypeText": "increased serum concentrations", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1449556772", + "literature": [ + "26164721", + "17108811", + "24598718", + "25446771", + "26774055", + "25673568", + "26367500", + "28350522", + "29469964" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "doxorubicin", + "drugId": "CHEMBL53463", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and hormone insensitive breast cancer may experience increased risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the CT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "amprenavir", + "drugId": "CHEMBL116", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with HIV infections and the TT genotype may have increased trough concentrations of amprenavir as compared to patients with the CC or CT genotypes. Note that this association was only found in patients of European descent, and not in African American or Hispanic patients. Other genetic and clinical factors may also affect concentrations of amprenavir in patients.", + "phenotypeText": "increased trough concentrations of amprenavir", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451116100", + "literature": [ + "23503447" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "irinotecan", + "drugId": "CHEMBL481", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype and cancer may have an increased risk of neutropenia when treated with irinotecan or irinotecan-based regimens, as compared to patients with the TT genotype. No significant results have been seen for diarrhea. Other genetic and clinical factors may also influence risk of neutropenia or diarrhea.", + "phenotypeText": "risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183615186", + "literature": [ + "19390945", + "18221820", + "18221820" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "idarubicin", + "drugId": "CHEMBL1117", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have an increased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "increased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "irinotecan", + "drugId": "CHEMBL481", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and cancer may have a decreased risk of neutropenia when treated with irinotecan or irinotecan-based regimens, as compared to patients with the CC or CT genotype. However, a different study of similar size found no association between the TT genotype and neutropenia. No significant results have been seen for diarrhea. Other genetic and clinical factors may also influence risk of neutropenia or diarrhea.", + "phenotypeText": "decreased risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183615186", + "literature": [ + "19390945", + "18221820", + "18221820" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "gemtuzumab ozogamicin", + "drugId": "CHEMBL1201506", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "decreased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "glucarpidase", + "drugId": "CHEMBL1863515", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients receiving methotrexate to treat acute lymphoblastic leukemia (ALL), and the rs4149056 CC genotype may be more likely to require glucarpidase treatment as compared to patients with the TT genotype. Other genetic and clinical factors may also influence likelihood of requiring glucarpidase treatment.", + "phenotypeText": "more likely to require glucarpidase treatment", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451721013", + "literature": [ + "33788417" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "rosuvastatin", + "drugId": "CHEMBL1496", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "The current evidence base suggests that there is no association between the rs4149056 CC genotype and the LDL-lowering response to rosuvastatin. Some studies report an association, however the majority of the studies documented no association. Other genetic and clinical factors may also influence response to rosuvastatin.", + "phenotypeText": "no association with LDL-lowering response to rosuvastatin", + "pgxCategory": "efficacy", + "evidenceLevel": "4", + "datasourceId": "pharmgkb", + "studyId": "1451358900", + "literature": [ + "20207952", + "22331829", + "31857620", + "22668755" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "lovastatin", + "drugId": "CHEMBL503", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have decreased concentration of lovastatin acid as compared to patients with the CC or CT genotype. Other genetic and clinical factors may also influence the metabolism of lovastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and lovastatin acid or lovastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "decreased concentration of lovastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451678112", + "literature": [ + "27967318", + "26020121" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "rifampin", + "drugId": "CHEMBL374478", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have increased plasma concentration of atorvastatin when treated concomitantly with rifampin as compared to patients with the CC or CT genotypes. Other genetic and clinical factors may also influence a patient's metabolism and response to atorvastatin.", + "phenotypeText": "increased plasma concentration of atorvastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981345311", + "literature": [ + "19374892" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "rosuvastatin", + "drugId": "CHEMBL1496", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have decreased risk of statin-related myopathy or myalgia when treated with rosuvastatin as compared to patients with genotype CT or CC. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect risk to rosuvastatin.", + "phenotypeText": "decreased risk of statin-related myopathy or myalgia", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451357200", + "literature": [ + "30595243", + "29950617", + "20347093", + "30250148", + "23708174", + "23942138", + "27839692", + "28812116" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "glucarpidase", + "drugId": "CHEMBL1863515", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients receiving methotrexate to treat acute lymphoblastic leukemia (ALL), and the rs4149056 CT genotype may be more likely to require glucarpidase treatment as compared to patients with the TT genotype. Other genetic and clinical factors may also influence likelihood of requiring glucarpidase treatment.", + "phenotypeText": "more likely to require glucarpidase treatment", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451721013", + "literature": [ + "33788417" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "pravastatin", + "drugId": "CHEMBL1144", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have decreased plasma concentrations of pravastatin as compared to patients with the CC or CT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence a patient's metabolism of pravastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and pravastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "decreased plasma concentrations of pravastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981345293", + "literature": [ + "30549267", + "26744986", + "15226675", + "16722833", + "16722833", + "15116054", + "16678544", + "17015053", + "17622941", + "12811365", + "19776292", + "18408565", + "17047488", + "15970799", + "17622941", + "17622941", + "17622941", + "17622941" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "gemtuzumab ozogamicin", + "drugId": "CHEMBL1201506", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype and an increased likelihood of toxic liver disease as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "decreased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "glucarpidase", + "drugId": "CHEMBL1863515", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients receiving methotrexate to treat acute lymphoblastic leukemia (ALL), and the rs4149056 TT genotype may be less likely to require glucarpidase treatment as compared to patients with the CC or CT genotypes. Other genetic and clinical factors may also influence likelihood of requiring glucarpidase treatment.", + "phenotypeText": "less likely to require glucarpidase treatment", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451721013", + "literature": [ + "33788417" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "cerivastatin", + "drugId": "CHEMBL1477", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have a lower risk of cerivastatin-related rhabdomyolysis as compared to patients with the CC or CT genotype. Other genetic and clinical factors may also influence a patient's risk for toxicity. Cerivastatin was withdrawn from the market because of 52 deaths attributed to drug-related rhabdomyolysis that lead to kidney failure.", + "phenotypeText": "lower risk of cerivastatin-related rhabdomyolysis", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981344897", + "literature": [ + "21386754" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and hormone insensitive breast cancer may experience increased risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the CT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "enalapril", + "drugId": "CHEMBL578", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and essential hypertension may have a decreased likelihood of cough when treated with enalapril as compared to patients with the CC and CT genotypes. Other genetic and clinical factors may also influence a patient's risk of cough when treated with enalapril.", + "phenotypeText": "decreased likelihood of cough", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1447953130", + "literature": [ + "26607661" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "fludarabine", + "drugId": "CHEMBL1568", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype and an increased likelihood of toxic liver disease as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "decreased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "fludarabine", + "drugId": "CHEMBL1568", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have an increased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "increased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "pravastatin", + "drugId": "CHEMBL1144", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have an increased risk of developing myopathy when treated with pravastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect a patient's risk of experiencing pravastatin-induced myopathy.", + "phenotypeText": "increased risk of developing myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244740", + "literature": [ + "23942138", + "27839692", + "19833260", + "19833260" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "methotrexate", + "drugId": "CHEMBL34259", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and Precursor Cell Lymphoblastic Leukemia-Lymphoma may need an increased dose of mercaptopurine, or methotrexate, as compared to children with the CC or CT genotypes. Other clinical and genetic factors may also influence dose of mercaptopurine or methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma.", + "phenotypeText": "increased dose", + "pgxCategory": "dosage", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449311190", + "literature": [ + "29683944" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "docetaxel", + "drugId": "CHEMBL92", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and hormone insensitive breast cancer may experience increased risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the CT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "atorvastatin", + "drugId": "CHEMBL1487", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have a decreased risk of myopathy when treated with atorvastatin as compared to patients with the CC or CT genotypes. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of developing myopathy when treated with atorvastatin.", + "phenotypeText": "decreased risk of myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1043880818", + "literature": [ + "32453264", + "32128760", + "30595243", + "28812116", + "26376374", + "30569848", + "34114646", + "33608664", + "33150478", + "21928084", + "21243006", + "23942138", + "24263182", + "26086347", + "27839692", + "28940218", + "19833260" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "simvastatin acid", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have increased serum concentrations of simvastatin acid as compared to patients with the TT genotype, but decreased concentrations as compared to patients with the CC genotype. This annotation only covers the pharmacokinetic relationship between rs4149056 and simvastatin acid and does not include evidence about clinical outcomes. Other genetic and clinical factors may also affect serum concentrations of simvastatin acid.", + "phenotypeText": "increased serum concentrations", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1449556772", + "literature": [ + "26164721", + "17108811", + "24598718", + "25446771", + "26774055", + "25673568", + "26367500", + "28350522", + "29469964" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "cytarabine", + "drugId": "CHEMBL803", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "decreased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "letermovir", + "drugId": "CHEMBL1241951", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have an increased AUC of letermovir as compared to patients with the TT genotype. Other genetic and clinical factors may also affect a patient's exposure to letermovir.", + "phenotypeText": "increased AUC of letermovir", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451105200", + "literature": [ + "31022310" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "rosuvastatin", + "drugId": "CHEMBL1496", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have increased risk of statin-related myopathy or myalgia when treated with rosuvastatin as compared to patients with genotype TT. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect risk to rosuvastatin.", + "phenotypeText": "increased risk of statin-related myopathy or myalgia", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451357200", + "literature": [ + "30595243", + "29950617", + "20347093", + "30250148", + "23708174", + "23942138", + "27839692", + "28812116" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "enalapril", + "drugId": "CHEMBL578", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype and essential hypertension may have an increased likelihood of cough when treated with enalapril as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's risk of cough when treated with enalapril.", + "phenotypeText": "increased likelihood of cough", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1447953130", + "literature": [ + "26607661" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "simvastatin acid", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have increased serum concentrations of simvastatin acid as compared to patients with the CT or TT genotypes. This annotation only covers the pharmacokinetic relationship between rs4149056 and simvastatin acid and does not include evidence about clinical outcomes. Other genetic and clinical factors may also affect serum concentrations of simvastatin acid.", + "phenotypeText": "increased serum concentrations of simvastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1449556772", + "literature": [ + "26164721", + "17108811", + "24598718", + "25446771", + "26774055", + "25673568", + "26367500", + "28350522", + "29469964" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "lopinavir", + "drugId": "CHEMBL729", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with HIV and the CT genotype may have decreased plasma levels of lopinavir as compared to patients with the CC genotype, but increased plasma levels as compared to patients with the TT genotype. However, one study failed to find this association. Other genetic and clinical factors may also influence lopinavir concentrations in a patients. This annotation only covers the pharmacokinetic relationship between rs4149056 and lopinavir and does not include evidence about clinical outcomes.", + "phenotypeText": "increased plasma levels", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444704359", + "literature": [ + "20051929", + "20078617", + "21743379", + "23503447", + "32022294", + "27142945", + "28718515" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "simvastatin", + "drugId": "CHEMBL1064", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have decreased lipid-lowering response to simvastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. The effect size may be small. Other genetic and clinical factors may also influence response to simvastatin.", + "phenotypeText": "decreased lipid-lowering response", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451356520", + "literature": [ + "30336686", + "29575099", + "25932441", + "28482130", + "28482130", + "20207952", + "24668570", + "23100282", + "24096969", + "22668755", + "23263738", + "25379722" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "rosuvastatin", + "drugId": "CHEMBL1496", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have higher plasma concentrations of rosuvastatin as compared to patients with the TT genotype. Other genetic and clinical factors may also influence metabolism of rosuvastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and rosuvastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "higher plasma concentrations of rosuvastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981345350", + "literature": [ + "29950617", + "31981411", + "27557342", + "17473846", + "23930675", + "23876492", + "25630984", + "31857620", + "32361904", + "25673568", + "16198652", + "30528195", + "17568401", + "17568401", + "17568401" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "gemtuzumab ozogamicin", + "drugId": "CHEMBL1201506", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype and an increased likelihood of toxic liver disease as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "increased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "gemtuzumab ozogamicin", + "drugId": "CHEMBL1201506", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have an increased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "increased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "cytarabine", + "drugId": "CHEMBL803", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype and an increased likelihood of toxic liver disease as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "increased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "lovastatin", + "drugId": "CHEMBL503", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have increased concentration of lovastatin acid as compared to patients with the TT genotype. Other genetic and clinical factors may also influence the metabolism of lovastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and lovastatin acid or lovastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased concentration of lovastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451678112", + "literature": [ + "27967318", + "26020121" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "pravastatin", + "drugId": "CHEMBL1144", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype who are treated with pravastatin may have a larger reduction in LDL and total cholesterol as compared to patients with the CC or CT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence a patient's response to pravastatin treatment.", + "phenotypeText": "larger reduction in LDL and total cholesterol", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1043880802", + "literature": [ + "25379722", + "22189199", + "15548849", + "17439540", + "16722833", + "16103896", + "21851379", + "16678544", + "18794729", + "18794729", + "16917677" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "rosuvastatin", + "drugId": "CHEMBL1496", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have higher plasma concentrations of rosuvastatin as compared to patients with the TT genotype. Other genetic and clinical factors may also influence metabolism of rosuvastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and rosuvastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "higher plasma concentrations of rosuvastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981345350", + "literature": [ + "29950617", + "31981411", + "27557342", + "17473846", + "23930675", + "23876492", + "25630984", + "31857620", + "32361904", + "25673568", + "16198652", + "30528195", + "17568401", + "17568401", + "17568401" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "lopinavir", + "drugId": "CHEMBL729", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with HIV and the CC genotype may have increased plasma levels of lopinavir as compared to patients with the CT or TT genotype. However, one study failed to find this association. Other genetic and clinical factors may also influence lopinavir concentrations in a patients. This annotation only covers the pharmacokinetic relationship between rs4149056 and lopinavir and does not include evidence about clinical outcomes.", + "phenotypeText": "increased plasma levels of lopinavir", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444704359", + "literature": [ + "20051929", + "20078617", + "21743379", + "23503447", + "32022294", + "27142945", + "28718515" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "methotrexate", + "drugId": "CHEMBL34259", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with precursor cell lymphoblastic leukemia-lymphoma and the rs4149056 CC genotype may have a decreased response to methotrexate as compared to patients with the CT and TT genotypes. However, conflicting evidence has been reported. Other clinical and genetic factors may also influence response to methotrexate.", + "phenotypeText": "decreased response to methotrexate", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449004841", + "literature": [ + "24386571", + "28525903" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "sn-38", + "drugId": "CHEMBL837", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and non-small cell lung cancer may have a decreased dose of SN-38 (as shown by an increased area under the concentration curve) when treated with irinotecan as compared to patients with the CC or CT genotype. SN-38 is the active metabolite of irinotecan. Other genetic and clinical factors may also influence dose of SN-38.", + "phenotypeText": "decreased dose of SN-38", + "pgxCategory": "dosage", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1043859108", + "literature": [ + "18221820" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "simvastatin", + "drugId": "CHEMBL1064", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have decreased serum concentrations of simvastatin acid as compared to patients with the CC or CT genotypes. This annotation only covers the pharmacokinetic relationship between rs4149056 and simvastatin acid and does not include evidence about clinical outcomes. Other genetic and clinical factors may also affect serum concentrations of simvastatin acid.", + "phenotypeText": "decreased serum concentrations of simvastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1449556772", + "literature": [ + "26164721", + "17108811", + "24598718", + "25446771", + "26774055", + "25673568", + "26367500", + "28350522", + "29469964" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "mycophenolate mofetil", + "drugId": "CHEMBL1456", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype and Kidney Transplantation who are treated with mycophenolate mofetil may have an increased risk of adverse drug reaction as compared to patients with the CC genotype and may have a decreased risk of adverse drug reaction as compared to patients with the TT genotype. However no association is found with increased risk of diarrhea or leukopenia. Other genetic and clinical factors may also influence a patient's risk for adverse drug reaction.", + "phenotypeText": "decreased risk of adverse drug reaction", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444607782", + "literature": [ + "21878834", + "21878834", + "21142914", + "21142914" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and hormone insensitive breast cancer may experience increased risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the CT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "atorvastatin", + "drugId": "CHEMBL1487", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have decreased plasma concentration of atorvastatin when treated concomitantly with rifampin as compared to patients with the TT genotypes. Other genetic and clinical factors may also influence a patient's metabolism and response to atorvastatin.", + "phenotypeText": "decreased plasma concentration", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981345311", + "literature": [ + "19374892" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "ticagrelor", + "drugId": "CHEMBL398435", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and acute coronary syndrome may have decreased concentrations of ticagrelor compared to patients with the CC and CT genotypes. Other factors may affect concentrations of ticagrelor.", + "phenotypeText": "decreased concentrations of ticagrelor", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448100347", + "literature": [ + "25935875" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "idarubicin", + "drugId": "CHEMBL1117", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype and an increased likelihood of toxic liver disease as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "decreased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "simvastatin", + "drugId": "CHEMBL1064", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have increased lipid-lowering response to simvastatin as compared to patients with the CC or CT genotype. However, conflicting evidence has been reported. The effect size may be small. Other genetic and clinical factors may also influence response to simvastatin.", + "phenotypeText": "increased lipid-lowering response", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451356520", + "literature": [ + "30336686", + "29575099", + "25932441", + "28482130", + "28482130", + "20207952", + "24668570", + "23100282", + "24096969", + "22668755", + "23263738", + "25379722" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "lovastatin acid", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have decreased concentrations of lovastatin acid as compared to patients with the CC or CT genotypes. Other genetic and clinical factors may also affect metabolism of lovastatin acid. This annotation only covers the pharmacokinetic relationship between rs4149056 and lovastatin acid and does not include evidence about clinical outcomes.", + "phenotypeText": "decreased concentrations of lovastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451244680", + "literature": [ + "27967318" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "rosuvastatin", + "drugId": "CHEMBL1496", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "The current evidence base suggests that there is no association between the rs4149056 TT genotype and the LDL-lowering response to rosuvastatin. Some studies report an association, however the majority of the studies documented no association. Other genetic and clinical factors may also influence response to rosuvastatin.", + "phenotypeText": "no association with LDL-lowering response to rosuvastatin", + "pgxCategory": "efficacy", + "evidenceLevel": "4", + "datasourceId": "pharmgkb", + "studyId": "1451358900", + "literature": [ + "20207952", + "22331829", + "31857620", + "22668755" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "simvastatin", + "drugId": "CHEMBL1064", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have a lower risk of simvastatin-related myopathy when treated with simvastatin as compared to patients with the CT or CC genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of toxicity to simvastatin.", + "phenotypeText": "lower risk of simvastatin-related myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "655384011", + "literature": [ + "29242847", + "28812116", + "18650507", + "18650507", + "21243006", + "23942138", + "24263182", + "27839692", + "28940218", + "19833260" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "atorvastatin", + "drugId": "CHEMBL1487", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have decreased exposure to atorvastatin as compared to patients with the CC or CT genotypes. Other genetic and clinical factors may also affect a patient's exposure to atorvastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and atorvastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "decreased exposure", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244800", + "literature": [ + "32128760", + "31594719", + "29442027", + "19374892", + "29039339", + "26857559", + "26373210", + "36622792", + "23361102", + "17473846", + "23876492", + "25673568", + "30528195", + "33805706", + "28435225", + "15970799", + "15970799", + "20040338", + "31594719", + "35034348" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "docetaxel", + "drugId": "CHEMBL92", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype and hormone insensitive breast cancer may experience lower risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the TT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "lower risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "lovastatin", + "drugId": "CHEMBL503", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have increased concentration of lovastatin acid as compared to patients with the TT genotype. Other genetic and clinical factors may also influence the metabolism of lovastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and lovastatin acid or lovastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased concentration of lovastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451678112", + "literature": [ + "27967318", + "26020121" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "sn-38", + "drugId": "CHEMBL837", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype and non-small cell lung cancer may have receive an increased dose of SN-38 (as shown by an increased area under the concentration curve) when treated with irinotecan as compared to patients with the TT genotype. SN-38 is the active metabolite of irinotecan. Other genetic and clinical factors may also influence dose of SN-38.", + "phenotypeText": "increased dose of SN-38", + "pgxCategory": "dosage", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1043859108", + "literature": [ + "18221820" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "sorafenib", + "drugId": "CHEMBL1336", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have decreased likelihood of developing Thrombocytopenia when treated with sorafenib as compared to patients with genotype TT or CT. Other genetic and clinical factors may also influence the response to sorafenib.", + "phenotypeText": "decreased likelihood of developing Thrombocytopenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448258741", + "literature": [ + "27533851" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "rosuvastatin", + "drugId": "CHEMBL1496", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "The current evidence base suggests that there is no association between the rs4149056 CT genotype and the LDL-lowering response to rosuvastatin. Some studies report an association, however the majority of the studies documented no association. Other genetic and clinical factors may also influence response to rosuvastatin.", + "phenotypeText": "no association with LDL-lowering response", + "pgxCategory": "efficacy", + "evidenceLevel": "4", + "datasourceId": "pharmgkb", + "studyId": "1451358900", + "literature": [ + "20207952", + "22331829", + "31857620", + "22668755" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "sorafenib", + "drugId": "CHEMBL1336", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have increased likelihood of developing Thrombocytopenia when treated with sorafenib as compared to patients with genotype CC. Other genetic and clinical factors may also influence the response to sorafenib.", + "phenotypeText": "increased likelihood of developing Thrombocytopenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448258741", + "literature": [ + "27533851" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "rosiglitazone", + "drugId": "CHEMBL121", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have decreased response to rosiglitazone in people with type II Diabetes Mellitus as compared to patients with genotype CC or CT. Other genetic and clinical factors may also influence the response to rosiglitazone.", + "phenotypeText": "decreased response to rosiglitazone", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448276473", + "literature": [ + "27271184" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "sn-38", + "drugId": "CHEMBL837", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype and non-small cell lung cancer may receive an increased dose of SN-38 (as shown by an increased area under the concentration curve) when treated with irinotecan as compared to patients with the TT genotype. SN-38 is the active metabolite of irinotecan. Other genetic and clinical factors may also influence dose of SN-38.", + "phenotypeText": "increased dose of SN-38", + "pgxCategory": "dosage", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1043859108", + "literature": [ + "18221820" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "enalapril", + "drugId": "CHEMBL578", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype and essential hypertension may have an increased likelihood of cough when treated with enalapril as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's risk of cough when treated with enalapril.", + "phenotypeText": "increased likelihood of cough", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1447953130", + "literature": [ + "26607661" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "fluvastatin", + "drugId": "CHEMBL2220442", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have increased concentrations of fluvastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect fluvastatin concentrations. This annotation only covers the pharmacokinetic relationship between rs4149056 and fluvastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased concentrations of fluvastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244700", + "literature": [ + "17015053", + "30989645" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "pitavastatin", + "drugId": "CHEMBL1201753", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have increased concentrations of pitavastatin when treated with pitavastatin as compared to patients with TT genotype. Other genetic and clinical factors may also influence the metabolism of pitavastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and pitavastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased concentrations of pitavastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451678210", + "literature": [ + "23556337", + "17460607" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "simvastatin", + "drugId": "CHEMBL1064", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have a higher risk of simvastatin-related myopathy when treated with simvastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of toxicity to simvastatin.", + "phenotypeText": "higher risk of simvastatin-related myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "655384011", + "literature": [ + "29242847", + "28812116", + "18650507", + "18650507", + "21243006", + "23942138", + "24263182", + "27839692", + "28940218", + "19833260" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "pravastatin", + "drugId": "CHEMBL1144", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have increased plasma concentrations of pravastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence a patient's metabolism of pravastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and pravastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased plasma concentrations of pravastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981345293", + "literature": [ + "30549267", + "26744986", + "15226675", + "16722833", + "16722833", + "15116054", + "16678544", + "17015053", + "17622941", + "12811365", + "19776292", + "18408565", + "17047488", + "15970799", + "17622941", + "17622941", + "17622941", + "17622941" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "repaglinide", + "drugId": "CHEMBL1272", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have decreased exposure of repaglinide and decreased response to repaglinide as compared to patients with the CC genotype and increased exposure as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a exposure of and response to repaglinide.", + "phenotypeText": "decreased exposure", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655384645", + "literature": [ + "18187595", + "29748863" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "cerivastatin", + "drugId": "CHEMBL1477", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have a higher risk of cerivastatin-related rhabdomyolysis as compared to patients with the CT or TT genotype. Other genetic and clinical factors may also influence a patient's risk for toxicity. Cerivastatin was withdrawn from the market because of 52 deaths attributed to drug-related rhabdomyolysis that lead to kidney failure.", + "phenotypeText": "higher risk of cerivastatin-related rhabdomyolysis", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981344897", + "literature": [ + "21386754" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "rosiglitazone", + "drugId": "CHEMBL121", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have increased response to rosiglitazone in people with type II Diabetes Mellitus as compared to patients with genotype TT. Other genetic and clinical factors may also influence the response to rosiglitazone.", + "phenotypeText": "increased response", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448276473", + "literature": [ + "27271184" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "cytarabine", + "drugId": "CHEMBL803", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have an increased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "increased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "atorvastatin", + "drugId": "CHEMBL1487", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have increased exposure to atorvastatin as compared to patients with the TT genotype. Other genetic and clinical factors may also affect a patient's exposure to atorvastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and atorvastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased exposure to atorvastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244800", + "literature": [ + "32128760", + "31594719", + "29442027", + "19374892", + "29039339", + "26857559", + "26373210", + "36622792", + "23361102", + "17473846", + "23876492", + "25673568", + "30528195", + "33805706", + "28435225", + "15970799", + "15970799", + "20040338", + "31594719", + "35034348" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "irinotecan", + "drugId": "CHEMBL481", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype and cancer may have an increased risk of neutropenia when treated with irinotecan or irinotecan-based regimens, as compared to patients with the TT genotype. However, a different study of similar size found no association between the CT genotype and neutropenia. No significant results have been seen for diarrhea. Other genetic and clinical factors may also influence risk of neutropenia or diarrhea.", + "phenotypeText": "increased risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183615186", + "literature": [ + "19390945", + "18221820", + "18221820" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "lovastatin acid", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have increased concentration of lovastatin acid as compared to patients with the TT genotype. Other genetic and clinical factors may also influence the metabolism of lovastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and lovastatin acid or lovastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased concentration of lovastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451678112", + "literature": [ + "27967318", + "26020121" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "mycophenolate mofetil", + "drugId": "CHEMBL1456", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype and Kidney Transplantation who are treated with mycophenolate mofetil may have an increased risk of adverse drug reaction as compared to patients with the CC genotype and may have a decreased risk of adverse drug reaction as compared to patients with the TT genotype. However no association is found with increased risk of diarrhea or leukopenia. Other genetic and clinical factors may also influence a patient's risk for adverse drug reaction.", + "phenotypeText": "increased risk of adverse drug reaction", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444607782", + "literature": [ + "21878834", + "21878834", + "21142914", + "21142914" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "lovastatin", + "drugId": "CHEMBL503", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have an increased risk of lovastatin-related myopathy when treated with lovastatin as compared to patients with the TT genotype. Other genetic and clinical factors may also influence risk of toxicity to lovastatin.", + "phenotypeText": "increased risk of lovastatin-related myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451465324", + "literature": [ + "34114646" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "cerivastatin", + "drugId": "CHEMBL1477", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have a higher risk of cerivastatin-related rhabdomyolysis as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's risk for toxicity. Cerivastatin was withdrawn from the market because of 52 deaths attributed to drug-related rhabdomyolysis that lead to kidney failure.", + "phenotypeText": "higher risk of cerivastatin-related rhabdomyolysis", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981344897", + "literature": [ + "21386754" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "simvastatin acid", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have decreased serum concentrations of simvastatin acid as compared to patients with the CC or CT genotypes. This annotation only covers the pharmacokinetic relationship between rs4149056 and simvastatin acid and does not include evidence about clinical outcomes. Other genetic and clinical factors may also affect serum concentrations of simvastatin acid.", + "phenotypeText": "decreased serum concentrations of simvastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1449556772", + "literature": [ + "26164721", + "17108811", + "24598718", + "25446771", + "26774055", + "25673568", + "26367500", + "28350522", + "29469964" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "simvastatin", + "drugId": "CHEMBL1064", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype may have a higher risk of simvastatin-related myopathy when treated with simvastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of toxicity to simvastatin.", + "phenotypeText": "higher risk of simvastatin-related myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "655384011", + "literature": [ + "29242847", + "28812116", + "18650507", + "18650507", + "21243006", + "23942138", + "24263182", + "27839692", + "28940218", + "19833260" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "repaglinide", + "drugId": "CHEMBL1272", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may experience increased repaglinide exposure and improved response as compared to patients with the CT or TT genotype. Other genetic and clinical factors may also influence a exposure of and response to repaglinide.", + "phenotypeText": "increased repaglinide exposure and improved response", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655384645", + "literature": [ + "18187595", + "29748863" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "simvastatin", + "drugId": "CHEMBL1064", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have increased serum concentrations of simvastatin acid as compared to patients with the CT or TT genotypes. This annotation only covers the pharmacokinetic relationship between rs4149056 and simvastatin acid and does not include evidence about clinical outcomes. Other genetic and clinical factors may also affect serum concentrations of simvastatin acid.", + "phenotypeText": "increased serum concentrations of simvastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1449556772", + "literature": [ + "26164721", + "17108811", + "24598718", + "25446771", + "26774055", + "25673568", + "26367500", + "28350522", + "29469964" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "doxorubicin", + "drugId": "CHEMBL53463", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype and hormone insensitive breast cancer may experience lower risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the TT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "lower risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "epirubicin", + "drugId": "CHEMBL417", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype and hormone insensitive breast cancer may experience lower risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the TT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "lower risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "fluvastatin", + "drugId": "CHEMBL2220442", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have an increased risk of developing myopathy when treated with fluvastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect a patient's risk of developing fluvastatin-induced myopathy.", + "phenotypeText": "increased risk of developing myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244720", + "literature": [ + "23942138", + "27839692" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "rifampin", + "drugId": "CHEMBL374478", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have decreased plasma concentration of atorvastatin when treated concomitantly with rifampin as compared to patients with the TT genotypes. Other genetic and clinical factors may also influence a patient's metabolism and response to atorvastatin.", + "phenotypeText": "decreased plasma concentration", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981345311", + "literature": [ + "19374892" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "sorafenib", + "drugId": "CHEMBL1336", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have increased likelihood of developing Thrombocytopenia when treated with sorafenib as compared to patients with genotype CC. Other genetic and clinical factors may also influence the response to sorafenib.", + "phenotypeText": "increased likelihood of developing Thrombocytopenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448258741", + "literature": [ + "27533851" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "fludarabine", + "drugId": "CHEMBL1568", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype and an increased likelihood of toxic liver disease as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "increased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "ticagrelor", + "drugId": "CHEMBL398435", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype and acute coronary syndrome may have increased concentrations of ticagrelor compared to patients with the TT genotype. Other factors may affect concentrations of ticagrelor.", + "phenotypeText": "increased concentrations of ticagrelor", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448100347", + "literature": [ + "25935875" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "pitavastatin", + "drugId": "CHEMBL1201753", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have decreased concentrations of pitavastatin when treated with pitavastatin as compared to patients with CC or CT genotype. Other genetic and clinical factors may also influence the metabolism of pitavastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and pitavastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "decreased concentrations of pitavastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451678210", + "literature": [ + "23556337", + "17460607" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "pravastatin", + "drugId": "CHEMBL1144", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have a decreased risk of developing myopathy when treated with pravastatin as compared to patients with the CC or CT genotypes. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect a patient's risk of experiencing pravastatin-induced myopathy.", + "phenotypeText": "decreased risk of developing myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244740", + "literature": [ + "23942138", + "27839692", + "19833260", + "19833260" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "idarubicin", + "drugId": "CHEMBL1117", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype and an increased likelihood of toxic liver disease as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "increased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "rosiglitazone", + "drugId": "CHEMBL121", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have increased response to rosiglitazone in people with type II Diabetes Mellitus as compared to patients with genotype TT. Other genetic and clinical factors may also influence the response to rosiglitazone.", + "phenotypeText": "increased response", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448276473", + "literature": [ + "27271184" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "pitavastatin", + "drugId": "CHEMBL1201753", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have increased concentrations of pitavastatin when treated with pitavastatin as compared to patients with TT genotype. Other genetic and clinical factors may also influence the metabolism of pitavastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and pitavastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased concentrations of pitavastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451678210", + "literature": [ + "23556337", + "17460607" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "fludarabine", + "drugId": "CHEMBL1568", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have a decreased likelihood of toxic liver disease when treated with cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin as compared to patients with the CC genotype. Other genetic and clinical factors may also influence a patient's response to cytarabine, fludarabine, gemtuzumab ozogamicin and idarubicin.", + "phenotypeText": "decreased likelihood of toxic liver disease", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1183684167", + "literature": [ + "22584460" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "docetaxel", + "drugId": "CHEMBL92", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype and hormone insensitive breast cancer may experience lower risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the TT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "lower risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "rosuvastatin", + "drugId": "CHEMBL1496", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have increased risk of statin-related myopathy or myalgia when treated with rosuvastatin as compared to patients with genotype TT. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect risk to rosuvastatin.", + "phenotypeText": "increased risk of statin-related myopathy or myalgia", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451357200", + "literature": [ + "30595243", + "29950617", + "20347093", + "30250148", + "23708174", + "23942138", + "27839692", + "28812116" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "epirubicin", + "drugId": "CHEMBL417", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype and hormone insensitive breast cancer may experience lower risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the TT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "lower risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "atorvastatin", + "drugId": "CHEMBL1487", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have increased exposure to atorvastatin as compared to patients with the TT genotype. Other genetic and clinical factors may also affect a patient's exposure to atorvastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and atorvastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased exposure to atorvastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244800", + "literature": [ + "32128760", + "31594719", + "29442027", + "19374892", + "29039339", + "26857559", + "26373210", + "36622792", + "23361102", + "17473846", + "23876492", + "25673568", + "30528195", + "33805706", + "28435225", + "15970799", + "15970799", + "20040338", + "31594719", + "35034348" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "hmg coa reductase inhibitors", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have a decreased risk of developing myopathy when treated with statins as compared to patients with the CC or CT genotypes. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect risk of statin-induced myopathy.", + "phenotypeText": "decreased risk of developing myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "981345382", + "literature": [ + "31242253", + "30250148", + "21178985", + "23942138", + "31220337", + "31967516", + "27595674", + "27839692", + "29785580", + "29785580" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "pravastatin", + "drugId": "CHEMBL1144", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have an increased risk of developing myopathy when treated with pravastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect a patient's risk of experiencing pravastatin-induced myopathy.", + "phenotypeText": "increased risk of developing myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244740", + "literature": [ + "23942138", + "27839692", + "19833260", + "19833260" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "fluvastatin", + "drugId": "CHEMBL2220442", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have a decreased risk of developing myopathy when treated with fluvastatin as compared to patients with the CC or CT genotypes. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect a patient's risk of developing fluvastatin-induced myopathy.", + "phenotypeText": "decreased risk of developing myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244720", + "literature": [ + "23942138", + "27839692" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "amprenavir", + "drugId": "CHEMBL116", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with HIV infections and the CC genotype may have decreased trough concentrations of amprenavir as compared to patients with the TT genotype. Note that this association was only found in patients of European descent, and not in African American or Hispanic patients. Other genetic and clinical factors may also affect concentrations of amprenavir in patients.", + "phenotypeText": "decreased trough concentrations of amprenavir", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451116100", + "literature": [ + "23503447" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "mycophenolate mofetil", + "drugId": "CHEMBL1456", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype and Kidney Transplantation who are treated with mycophenolate mofetil may have a decreased risk of adverse drug reaction as compared to patients with the TT genotype. However no association is found with increased risk of diarrhea or leukopenia. Other genetic and clinical factors may also influence a patient's risk for adverse drug reaction.", + "phenotypeText": "decreased risk of adverse drug reaction", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444607782", + "literature": [ + "21878834", + "21878834", + "21142914", + "21142914" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "repaglinide", + "drugId": "CHEMBL1272", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have decreased exposure of repaglinide and decreased response to repaglinide compared to patients with the CC genotype. Other genetic and clinical factors may also influence a exposure of and response to repaglinide.", + "phenotypeText": "decreased exposure and response to repaglinide", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655384645", + "literature": [ + "18187595", + "29748863" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "lovastatin acid", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have increased concentrations of lovastatin acid as compared to patients with the TT genotype. Other genetic and clinical factors may also affect metabolism of lovastatin acid. This annotation only covers the pharmacokinetic relationship between rs4149056 and lovastatin acid and does not include evidence about clinical outcomes.", + "phenotypeText": "increased concentrations of lovastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451244680", + "literature": [ + "27967318" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype and hormone insensitive breast cancer may experience lower risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the TT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "lower risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "rosuvastatin", + "drugId": "CHEMBL1496", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have lower plasma concentrations of rosuvastatin as compared to patients with the CC genotype. Other genetic and clinical factors may also influence metabolism of rosuvastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and rosuvastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "lower plasma concentrations of rosuvastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981345350", + "literature": [ + "29950617", + "31981411", + "27557342", + "17473846", + "23930675", + "23876492", + "25630984", + "31857620", + "32361904", + "25673568", + "16198652", + "30528195", + "17568401", + "17568401", + "17568401" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "pravastatin", + "drugId": "CHEMBL1144", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CT genotype who are treated with pravastatin may have a smaller reduction in LDL and total cholesterol as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence a patient's response to pravastatin treatment.", + "phenotypeText": "smaller reduction in LDL and total cholesterol", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1043880802", + "literature": [ + "25379722", + "22189199", + "15548849", + "17439540", + "16722833", + "16103896", + "21851379", + "16678544", + "18794729", + "18794729", + "16917677" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "lovastatin acid", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have increased concentration of lovastatin acid as compared to patients with the TT genotype. Other genetic and clinical factors may also influence the metabolism of lovastatin. This annotation only covers the pharmacokinetic relationship between rs4149056 and lovastatin acid or lovastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased concentration of lovastatin acid", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451678112", + "literature": [ + "27967318", + "26020121" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "atorvastatin", + "drugId": "CHEMBL1487", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have decreased plasma concentration of atorvastatin when treated concomitantly with rifampin as compared to patients with the TT genotypes. Other genetic and clinical factors may also influence a patient's metabolism and response to atorvastatin.", + "phenotypeText": "decreased plasma concentration", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981345311", + "literature": [ + "19374892" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "methotrexate", + "drugId": "CHEMBL34259", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Pediatric patients with the rs4149056 TT genotype and cancers may have increased clearance of methotrexate as compared to patients with the CC or CT genotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between rs4149056 and methotrexate and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence clearance of methotrexate.", + "phenotypeText": "increased clearance of methotrexate", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655387949", + "literature": [ + "23233662", + "19901119", + "31870219", + "33501733", + "23652803", + "25098908", + "24712521", + "28525903", + "29791011" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "methotrexate", + "drugId": "CHEMBL34259", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with precursor cell lymphoblastic leukemia-lymphoma and the rs4149056 TT genotype may have an increased response to methotrexate as compared to patients with the CC genotype. However, conflicting evidence has been reported. Other clinical and genetic factors may also influence response to methotrexate.", + "phenotypeText": "increased response to methotrexate", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449004841", + "literature": [ + "24386571", + "28525903" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "fluvastatin", + "drugId": "CHEMBL2220442", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have increased concentrations of fluvastatin as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect fluvastatin concentrations. This annotation only covers the pharmacokinetic relationship between rs4149056 and fluvastatin and does not include evidence about clinical outcomes.", + "phenotypeText": "increased concentrations of fluvastatin", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451244700", + "literature": [ + "17015053", + "30989645" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "lovastatin", + "drugId": "CHEMBL503", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 TT genotype may have a decreased risk of lovastatin-related myopathy when treated with lovastatin as compared to patients with the CC genotype. Other genetic and clinical factors may also influence risk of toxicity to lovastatin.", + "phenotypeText": "decreased risk of lovastatin-related myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451465324", + "literature": [ + "34114646" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "letermovir", + "drugId": "CHEMBL1241951", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have a decreased AUC of letermovir as compared to patients with the CC or CT genotypes. Other genetic and clinical factors may also affect a patient's exposure to letermovir.", + "phenotypeText": "decreased AUC of letermovir", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451105200", + "literature": [ + "31022310" + ] + }, + { + "genotypeId": "12_21178615_T_C,C", + "isDirectTarget": false, + "drugFromSource": "hmg coa reductase inhibitors", + "drugId": null, + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs4149056 CC genotype may have an increased risk of developing myopathy when treated with statins as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also affect risk of statin-induced myopathy.", + "phenotypeText": "increased risk of developing myopathy", + "pgxCategory": "toxicity", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "981345382", + "literature": [ + "31242253", + "30250148", + "21178985", + "23942138", + "31220337", + "31967516", + "27595674", + "27839692", + "29785580", + "29785580" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "mercaptopurine", + "drugId": "CHEMBL1425", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and Precursor Cell Lymphoblastic Leukemia-Lymphoma may need an increased dose of mercaptopurine, or methotrexate, as compared to children with the CC or CT genotypes. Other clinical and genetic factors may also influence dose of mercaptopurine or methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma.", + "phenotypeText": "increased dose", + "pgxCategory": "dosage", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449311190", + "literature": [ + "29683944" + ] + }, + { + "genotypeId": "12_21178615_T_T,T", + "isDirectTarget": false, + "drugFromSource": "mycophenolate mofetil", + "drugId": "CHEMBL1456", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype and Kidney Transplantation who are treated with mycophenolate mofetil may have an increased risk of adverse drug reaction as compared to patients with the CC genotype. However no association is found with increased risk of diarrhea or leukopenia. Other genetic and clinical factors may also influence a patient's risk for adverse drug reaction.", + "phenotypeText": "increased risk of adverse drug reaction", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444607782", + "literature": [ + "21878834", + "21878834", + "21142914", + "21142914" + ] + }, + { + "genotypeId": "12_21178615_T_C,T", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype and hormone insensitive breast cancer may experience lower risk of chemotherapy-induced amenorrhea when treated with goserelin or combinations of cyclophosphamide, docetaxel, doxorubicin, epirubicin, and fluorouracil compared to patients with the TT genotype. Other clinical and genetic factors may affect a patient's risk of chemotherapy-induced amenorrhea.", + "phenotypeText": "lower risk of chemotherapy-induced amenorrhea", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1448112147", + "literature": [ + "27234217" + ] + }, + { + "genotypeId": "16_31096368_C_C,T", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CT genotype may have an increased risk of bleeding when treated with warfarin as compared to patients with the CC genotypes. However, conflicting evidence has been reported. Other clinical and genetic factors may also influence risk of warfarin-induced bleeding.", + "phenotypeText": "increased risk of bleeding", + "pgxCategory": "toxicity", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1449269910", + "literature": [ + "25521356", + "27262824", + "25769357", + "24919870", + "23423913", + "18574025", + "18690342", + "23602689", + "21148049", + "25244877", + "26445138", + "26777610", + "18950464", + "22571356", + "24474498", + "25001883", + "23932037", + "23774101", + "23104259", + "22592842", + "27488176", + "27581200", + "28033245", + "28689179", + "29432897", + "29577257" + ] + }, + { + "genotypeId": "16_31096368_C_C,C", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CC genotype may have decreased risk of over-anticoagulation when treated with warfarin as compared with patients with genotype TT or CT. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence the toxicity to warfarin.", + "phenotypeText": "decreased risk of over-anticoagulation", + "pgxCategory": "toxicity", + "evidenceLevel": "1B", + "datasourceId": "pharmgkb", + "studyId": "1447673005", + "literature": [ + "25769357", + "18690342", + "23104259", + "23602689", + "25244877", + "26445138", + "19794411", + "22990331", + "23279643", + "21318593", + "26739746", + "19874474", + "22571356", + "18574025", + "23932037", + "28033245", + "28049362" + ] + }, + { + "genotypeId": "16_31096368_C_C,T", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CT genotype may require shorter time to therapeutic INR when treated with warfarin as compared with patients with genotype CC. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence the response to warfarin.", + "phenotypeText": "shorter time to therapeutic INR", + "pgxCategory": "efficacy", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1447672998", + "literature": [ + "18574025", + "22571356", + "19794411", + "20386359", + "21318593", + "20339978", + "23279643", + "24474498", + "22571356", + "18322281", + "28382498", + "29432897" + ] + }, + { + "genotypeId": "16_31096368_C_C,T", + "isDirectTarget": true, + "drugFromSource": "acenocoumarol", + "drugId": "CHEMBL397420", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype who are treated with acenocoumarol may have an increased risk of Hemorrhage as compared to the CC genotypes. Other clinical and genetic factors may also influence risk of hemorrhage in patients administered acetacoumarol.", + "phenotypeText": "increased risk of Hemorrhage", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451243628", + "literature": [ + "24919870", + "21148049", + "23113310", + "18950464", + "28033245", + "29432897", + "29577257" + ] + }, + { + "genotypeId": "16_31096368_C_C,C", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CC genotype may spent more time in INR therapeutic range (TTR) when treated with warfarin as compared with patients with genotype TT or CT. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence the response to warfarin.", + "phenotypeText": "more time in INR therapeutic range (TTR)", + "pgxCategory": "efficacy", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1447673015", + "literature": [ + "18574025", + "18690342", + "22130800", + "25001883", + "22592842", + "18322281", + "31720756", + "27511999", + "29396738" + ] + }, + { + "genotypeId": "16_31096368_C_T,T", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 TT genotype may have increased risk of over-anticoagulation when treated with warfarin as compared with patients with genotype CC. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence the toxicity to warfarin.", + "phenotypeText": "increased risk of over-anticoagulation", + "pgxCategory": "toxicity", + "evidenceLevel": "1B", + "datasourceId": "pharmgkb", + "studyId": "1447673005", + "literature": [ + "25769357", + "18690342", + "23104259", + "23602689", + "25244877", + "26445138", + "19794411", + "22990331", + "23279643", + "21318593", + "26739746", + "19874474", + "22571356", + "18574025", + "23932037", + "28033245", + "28049362" + ] + }, + { + "genotypeId": "16_31096368_C_T,T", + "isDirectTarget": true, + "drugFromSource": "phenprocoumon", + "drugId": "CHEMBL1465", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 TT genotype may require a lower dose when treated with phenprocoumon as compared to patients with the CC genotype. Other genetic and clinical factors may also influence phenprocoumon dose.", + "phenotypeText": "lower dose requirement", + "pgxCategory": "dosage", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451237940", + "literature": [ + "20833980", + "24224579", + "23423913", + "23299853", + "18629445", + "21110013", + "20376629", + "21057703", + "26984978", + "21636598" + ] + }, + { + "genotypeId": "16_31096368_C_T,T", + "isDirectTarget": true, + "drugFromSource": "acenocoumarol", + "drugId": "CHEMBL397420", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 TT genotype may require a decreased dose as of acenocoumarol compared to patients with the CC genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence acenocoumarol dose requirements.", + "phenotypeText": "require a decreased dose", + "pgxCategory": "dosage", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981204044", + "literature": [ + "23774941", + "25519826", + "23481074", + "24956252", + "19277427", + "16611310", + "19875892", + "22486182", + "19018719", + "22629463", + "23159639", + "23159639", + "22486182", + "22486182", + "23473641", + "23651023", + "23651023", + "21148049", + "24108193", + "25042728", + "27335128", + "21636598", + "22911785", + "25089947" + ] + }, + { + "genotypeId": "16_31096368_C_C,C", + "isDirectTarget": true, + "drugFromSource": "acenocoumarol", + "drugId": "CHEMBL397420", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CC genotype may require an increased dose of acenocoumarol as compared to patients with the TT and CT genotypes. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence acenocoumarol dose requirements.", + "phenotypeText": "require an increased dose of acenocoumarol", + "pgxCategory": "dosage", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981204044", + "literature": [ + "23774941", + "25519826", + "23481074", + "24956252", + "19277427", + "16611310", + "19875892", + "22486182", + "19018719", + "22629463", + "23159639", + "23159639", + "22486182", + "22486182", + "23473641", + "23651023", + "23651023", + "21148049", + "24108193", + "25042728", + "27335128", + "21636598", + "22911785", + "25089947" + ] + }, + { + "genotypeId": "16_31096368_C_C,C", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CC genotype may require an increased dose of warfarin as compared to patients with the CT or TT genotype. Other genetic and clinical factors may also influence warfarin dose requirement.", + "phenotypeText": "require an increased dose of warfarin", + "pgxCategory": "dosage", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "655385012", + "literature": [ + "25084205", + "24601977", + "25312789", + "25594941", + "20833980", + "22990331", + "23061746", + "20375999", + "28049362", + "31902949", + "31114289", + "19582440", + "21176721", + "26024874", + "20615525", + "26219158", + "23602689", + "26445138", + "26433837", + "20386359", + "20339978", + "26739746", + "26745506", + "20653676", + "19875892", + "21185752", + "20833655", + "18030307", + "18542936", + "19387626", + "20072124", + "19135231", + "17510308", + "15947090", + "16890578", + "18855533", + "19874474", + "22010099", + "22130800", + "19794411", + "15883587", + "15888487", + "18305455", + "15930419", + "16580898", + "22040439", + "21174619", + "21148049", + "21110192", + "21747589", + "22528326", + "22676192", + "20203262", + "18535201", + "19300499", + "19300499", + "19228618", + "17049586", + "21228733", + "22349464", + "23990957", + "18574025", + "19679631", + "20421126", + "24019055", + "20128861", + "24474498", + "22158446", + "25001883", + "23949431", + "23104259", + "22854539", + "22592842", + "22571356", + "22274142", + "21320153", + "25042728", + "24029542", + "24330000", + "19745563", + "31395958", + "28429387", + "28550460", + "28382498", + "27617219", + "29568565", + "29781049" + ] + }, + { + "genotypeId": "16_31096368_C_C,T", + "isDirectTarget": true, + "drugFromSource": "acenocoumarol", + "drugId": "CHEMBL397420", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CT genotype may require a decreased dose of acenocoumarol as compared to patients with the CC genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence acenocoumarol dose requirements.", + "phenotypeText": "decreased dose requirement", + "pgxCategory": "dosage", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981204044", + "literature": [ + "23774941", + "25519826", + "23481074", + "24956252", + "19277427", + "16611310", + "19875892", + "22486182", + "19018719", + "22629463", + "23159639", + "23159639", + "22486182", + "22486182", + "23473641", + "23651023", + "23651023", + "21148049", + "24108193", + "25042728", + "27335128", + "21636598", + "22911785", + "25089947" + ] + }, + { + "genotypeId": "16_31096368_C_C,T", + "isDirectTarget": true, + "drugFromSource": "phenprocoumon", + "drugId": "CHEMBL1465", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CT genotype may require a lower dose when treated with phenprocoumon as compared to patients with the CC genotype. Other genetic and clinical factors may also influence phenprocoumon dose.", + "phenotypeText": "lower dose requirement", + "pgxCategory": "dosage", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451237940", + "literature": [ + "20833980", + "24224579", + "23423913", + "23299853", + "18629445", + "21110013", + "20376629", + "21057703", + "26984978", + "21636598" + ] + }, + { + "genotypeId": "16_31096368_C_T,T", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 TT genotype may spent less time in INR therapeutic range (TTR) when treated with warfarin as compared with patients with genotype CC. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence the response to warfarin.", + "phenotypeText": "less time in INR therapeutic range (TTR)", + "pgxCategory": "efficacy", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1447673015", + "literature": [ + "18574025", + "18690342", + "22130800", + "25001883", + "22592842", + "18322281", + "31720756", + "27511999", + "29396738" + ] + }, + { + "genotypeId": "16_31096368_C_C,C", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CC genotype may have a decreased risk of bleeding when treated with warfarin as compared to patients with the CT or TT genotypes. However, conflicting evidence has been reported. Other clinical and genetic factors may also influence risk of warfarin-induced bleeding.", + "phenotypeText": "decreased risk of bleeding", + "pgxCategory": "toxicity", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1449269910", + "literature": [ + "25521356", + "27262824", + "25769357", + "24919870", + "23423913", + "18574025", + "18690342", + "23602689", + "21148049", + "25244877", + "26445138", + "26777610", + "18950464", + "22571356", + "24474498", + "25001883", + "23932037", + "23774101", + "23104259", + "22592842", + "27488176", + "27581200", + "28033245", + "28689179", + "29432897", + "29577257" + ] + }, + { + "genotypeId": "16_31096368_C_C,T", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CT genotype may have increased risk of over-anticoagulation when treated with warfarin as compared with patients with genotype CC. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence the toxicity to warfarin.", + "phenotypeText": "increased risk of over-anticoagulation", + "pgxCategory": "toxicity", + "evidenceLevel": "1B", + "datasourceId": "pharmgkb", + "studyId": "1447673005", + "literature": [ + "25769357", + "18690342", + "23104259", + "23602689", + "25244877", + "26445138", + "19794411", + "22990331", + "23279643", + "21318593", + "26739746", + "19874474", + "22571356", + "18574025", + "23932037", + "28033245", + "28049362" + ] + }, + { + "genotypeId": "16_31096368_C_C,C", + "isDirectTarget": true, + "drugFromSource": "phenprocoumon", + "drugId": "CHEMBL1465", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CC genotype may require a higher dose when treated with phenprocoumon as compared to patients with the TT or CT genotype. Other genetic and clinical factors may also influence phenprocoumon dose.", + "phenotypeText": "require a higher dose", + "pgxCategory": "dosage", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451237940", + "literature": [ + "20833980", + "24224579", + "23423913", + "23299853", + "18629445", + "21110013", + "20376629", + "21057703", + "26984978", + "21636598" + ] + }, + { + "genotypeId": "16_31096368_C_C,C", + "isDirectTarget": true, + "drugFromSource": "phenprocoumon", + "drugId": "CHEMBL1465", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype may have a decreased risk of adverse events (bleeding, over-anticoagulation or increased time above therapeutic range) when treated with phenprocoumon as compared to patients with the TT or CT genotype. Other clinical and genetic factors may also influence risk of adverse events to phenprocoumon.", + "phenotypeText": "decreased risk of adverse events", + "pgxCategory": "toxicity", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1451243676", + "literature": [ + "23423913", + "23016521", + "21057703", + "23016521" + ] + }, + { + "genotypeId": "16_31096368_C_C,T", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CT genotype may require a decreased dose of warfarin as compared to patients with the CC genotype or an increased dose as compared to patients with the TT genotype. Other genetic and clinical factors may also influence warfarin dose requirement.", + "phenotypeText": "decreased or increased dose requirement of warfarin", + "pgxCategory": "dosage", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "655385012", + "literature": [ + "25084205", + "24601977", + "25312789", + "25594941", + "20833980", + "22990331", + "23061746", + "20375999", + "28049362", + "31902949", + "31114289", + "19582440", + "21176721", + "26024874", + "20615525", + "26219158", + "23602689", + "26445138", + "26433837", + "20386359", + "20339978", + "26739746", + "26745506", + "20653676", + "19875892", + "21185752", + "20833655", + "18030307", + "18542936", + "19387626", + "20072124", + "19135231", + "17510308", + "15947090", + "16890578", + "18855533", + "19874474", + "22010099", + "22130800", + "19794411", + "15883587", + "15888487", + "18305455", + "15930419", + "16580898", + "22040439", + "21174619", + "21148049", + "21110192", + "21747589", + "22528326", + "22676192", + "20203262", + "18535201", + "19300499", + "19300499", + "19228618", + "17049586", + "21228733", + "22349464", + "23990957", + "18574025", + "19679631", + "20421126", + "24019055", + "20128861", + "24474498", + "22158446", + "25001883", + "23949431", + "23104259", + "22854539", + "22592842", + "22571356", + "22274142", + "21320153", + "25042728", + "24029542", + "24330000", + "19745563", + "31395958", + "28429387", + "28550460", + "28382498", + "27617219", + "29568565", + "29781049" + ] + }, + { + "genotypeId": "16_31096368_C_C,T", + "isDirectTarget": true, + "drugFromSource": "phenprocoumon", + "drugId": "CHEMBL1465", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CT genotype may have an increased risk of adverse events (bleeding, over-anticoagulation or increased time above therapeutic range) when treated with phenprocoumon as compared to patients with the CC genotype. Other clinical and genetic factors may also influence risk of adverse events to phenprocoumon.", + "phenotypeText": "increased risk of adverse events", + "pgxCategory": "toxicity", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1451243676", + "literature": [ + "23423913", + "23016521", + "21057703", + "23016521" + ] + }, + { + "genotypeId": "16_31096368_C_T,T", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 TT genotype may have an increased risk of bleeding when treated with warfarin as compared to the CC genotypes. However, conflicting evidence has been reported. Other clinical and genetic factors may also influence risk of warfarin-induced bleeding.", + "phenotypeText": "increased risk of bleeding", + "pgxCategory": "toxicity", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1449269910", + "literature": [ + "25521356", + "27262824", + "25769357", + "24919870", + "23423913", + "18574025", + "18690342", + "23602689", + "21148049", + "25244877", + "26445138", + "26777610", + "18950464", + "22571356", + "24474498", + "25001883", + "23932037", + "23774101", + "23104259", + "22592842", + "27488176", + "27581200", + "28033245", + "28689179", + "29432897", + "29577257" + ] + }, + { + "genotypeId": "16_31096368_C_T,T", + "isDirectTarget": true, + "drugFromSource": "acenocoumarol", + "drugId": "CHEMBL397420", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype who are treated with acenocoumarol may have an increased risk of Hemorrhage as compared to the CC genotypes. Other clinical and genetic factors may also influence risk of hemorrhage in patients administered acetacoumarol.", + "phenotypeText": "increased risk of Hemorrhage", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451243628", + "literature": [ + "24919870", + "21148049", + "23113310", + "18950464", + "28033245", + "29432897", + "29577257" + ] + }, + { + "genotypeId": "16_31096368_C_T,T", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 TT genotype may require a decreased dose of warfarin as compared to patients with the CC or CT genotype. Other genetic and clinical factors may also influence warfarin dose requirement.", + "phenotypeText": "decreased dose requirement of warfarin", + "pgxCategory": "dosage", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "655385012", + "literature": [ + "25084205", + "24601977", + "25312789", + "25594941", + "20833980", + "22990331", + "23061746", + "20375999", + "28049362", + "31902949", + "31114289", + "19582440", + "21176721", + "26024874", + "20615525", + "26219158", + "23602689", + "26445138", + "26433837", + "20386359", + "20339978", + "26739746", + "26745506", + "20653676", + "19875892", + "21185752", + "20833655", + "18030307", + "18542936", + "19387626", + "20072124", + "19135231", + "17510308", + "15947090", + "16890578", + "18855533", + "19874474", + "22010099", + "22130800", + "19794411", + "15883587", + "15888487", + "18305455", + "15930419", + "16580898", + "22040439", + "21174619", + "21148049", + "21110192", + "21747589", + "22528326", + "22676192", + "20203262", + "18535201", + "19300499", + "19300499", + "19228618", + "17049586", + "21228733", + "22349464", + "23990957", + "18574025", + "19679631", + "20421126", + "24019055", + "20128861", + "24474498", + "22158446", + "25001883", + "23949431", + "23104259", + "22854539", + "22592842", + "22571356", + "22274142", + "21320153", + "25042728", + "24029542", + "24330000", + "19745563", + "31395958", + "28429387", + "28550460", + "28382498", + "27617219", + "29568565", + "29781049" + ] + }, + { + "genotypeId": "16_31096368_C_T,T", + "isDirectTarget": true, + "drugFromSource": "phenprocoumon", + "drugId": "CHEMBL1465", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the TT genotype may have an increased risk of adverse events (bleeding, over-anticoagulation or increased time above therapeutic range) when treated with phenprocoumon as compared to patients with the CC genotype. Other clinical and genetic factors may also influence risk of adverse events to phenprocoumon.", + "phenotypeText": "increased risk of adverse events", + "pgxCategory": "toxicity", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1451243676", + "literature": [ + "23423913", + "23016521", + "21057703", + "23016521" + ] + }, + { + "genotypeId": "16_31096368_C_C,T", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CT genotype may spent less time in INR therapeutic range (TTR) when treated with warfarin as compared with patients with genotype CC. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence the response to warfarin.", + "phenotypeText": "less time in INR therapeutic range (TTR)", + "pgxCategory": "efficacy", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1447673015", + "literature": [ + "18574025", + "18690342", + "22130800", + "25001883", + "22592842", + "18322281", + "31720756", + "27511999", + "29396738" + ] + }, + { + "genotypeId": "16_31096368_C_C,C", + "isDirectTarget": true, + "drugFromSource": "acenocoumarol", + "drugId": "CHEMBL397420", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the CC genotype who are treated with acenocoumarol may have a decreased risk of Hemorrhage as compared to the CT or TT genotypes. Other clinical and genetic factors may also influence risk of hemorrhage in patients administered acetacoumarol.", + "phenotypeText": "decreased risk of hemorrhage", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1451243628", + "literature": [ + "24919870", + "21148049", + "23113310", + "18950464", + "28033245", + "29432897", + "29577257" + ] + }, + { + "genotypeId": "16_31096368_C_C,C", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 CC genotype may require longer time to therapeutic INR when treated with warfarin as compared with patients with genotype TT or CT. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence the response to warfarin.", + "phenotypeText": "require longer time to therapeutic INR", + "pgxCategory": "efficacy", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1447672998", + "literature": [ + "18574025", + "22571356", + "19794411", + "20386359", + "21318593", + "20339978", + "23279643", + "24474498", + "22571356", + "18322281", + "28382498", + "29432897" + ] + }, + { + "genotypeId": "16_31096368_C_T,T", + "isDirectTarget": true, + "drugFromSource": "warfarin", + "drugId": "CHEMBL1464", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs9923231 TT genotype may require shorter time to therapeutic INR when treated with warfarin as compared with patients with genotype CC. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence the response to warfarin.", + "phenotypeText": "shorter time to therapeutic INR", + "pgxCategory": "efficacy", + "evidenceLevel": "2A", + "datasourceId": "pharmgkb", + "studyId": "1447672998", + "literature": [ + "18574025", + "22571356", + "19794411", + "20386359", + "21318593", + "20339978", + "23279643", + "24474498", + "22571356", + "18322281", + "28382498", + "29432897" + ] + }, + { + "genotypeId": "10_94781859_G_A,G", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with AG genotype and breast cancer may have an increased risk of neutropenia when treated with cyclophosphamide, doxorubicin and fluorouracil (FAC) as compared to patients with the GG genotype. Other genetic and clinical factors may also affect the risk for neutropenia in patients taking FAC chemotherapy.", + "phenotypeText": "increased risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449718271", + "literature": [ + "29507678" + ] + }, + { + "genotypeId": "10_94781859_G_A,A", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AA genotype and Systemic Lupus Erythematosus who are treated with cyclophosphamide may have decreased metabolism of cyclophosphamide, leading to lower concentrations of the active metabolite and a decreased risk of toxicity (ovarian, gastrointestinal, or hematological) as compared to patients with the GG genotype. Other genetic and clinical factors may also influence a patient's risk for cyclophosphamide-induced toxicity.", + "phenotypeText": "decreased risk of toxicity", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981202562", + "literature": [ + "26456622", + "26456622", + "20358205" + ] + }, + { + "genotypeId": "10_94781859_G_G,G", + "isDirectTarget": false, + "drugFromSource": "venlafaxine", + "drugId": "CHEMBL637", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the GG genotype and depression who are treated with venlafaxine may have a decreased, but not absent, risk for agitation and dysphoria as compared to patients with the AG genotype. Other genetic and clinical factors may also influence a patient's risk for treatment side effects.", + "phenotypeText": "decreased risk for agitation and dysphoria", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444703063", + "literature": [ + "23799451" + ] + }, + { + "genotypeId": "10_94781859_G_A,G", + "isDirectTarget": false, + "drugFromSource": "nelfinavir", + "drugId": "CHEMBL584", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AG genotype and pancreatic cancer or HIV may have decreased metabolism and increased concentrations of nelfinavir as compared to patients with the GG genotype. Other genetic and clinical factors may also influence metabolism and concentration of nelfinavir.", + "phenotypeText": "decreased metabolism and increased concentrations of nelfinavir", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1447962874", + "literature": [ + "16267764", + "25752914", + "25752914" + ] + }, + { + "genotypeId": "10_94781859_G_A,G", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AG genotype and Breast Cancer who are treated with cyclophosphamide and doxorubicin may have a decreased risk of poorer outcome as compared to patients with the AA genotype. Other genetic and clinical factors may also influence a patient's response to treatment.", + "phenotypeText": "decreased risk of poorer outcome", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981202551", + "literature": [ + "20179710", + "29938344" + ] + }, + { + "genotypeId": "10_94781859_G_A,A", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with AA genotype and breast cancer may have an increased risk of neutropenia when treated with cyclophosphamide, doxorubicin and fluorouracil (FAC) as compared to patients with the GG genotype. Other genetic and clinical factors may also affect the risk for neutropenia in patients taking FAC chemotherapy.", + "phenotypeText": "increased risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449718271", + "literature": [ + "29507678" + ] + }, + { + "genotypeId": "10_94781859_G_A,G", + "isDirectTarget": false, + "drugFromSource": "prasugrel", + "drugId": "CHEMBL1201772", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AG genotype who are treated with prasugrel may have a higher rate of high on-treatment platelet reactivity at 1 month of treatment as compared to patients with the GG genotype. However, contradictory findings are reported. Other genetic and clinical factors may also influence a patient's response to prasugrel.", + "phenotypeText": "higher rate of high on-treatment platelet reactivity", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "982040598", + "literature": [ + "23257377", + "23257377", + "17900275", + "17900275" + ] + }, + { + "genotypeId": "10_94781859_G_A,G", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with AG genotype and breast cancer may have an increased risk of neutropenia when treated with cyclophosphamide, doxorubicin and fluorouracil (FAC) as compared to patients with the GG genotype. Other genetic and clinical factors may also affect the risk for neutropenia in patients taking FAC chemotherapy.", + "phenotypeText": "increased risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449718271", + "literature": [ + "29507678" + ] + }, + { + "genotypeId": "10_94781859_G_A,G", + "isDirectTarget": false, + "drugFromSource": "venlafaxine", + "drugId": "CHEMBL637", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AG genotype and depression who are treated with venlafaxine may have an increased risk for agitation and dysphoria as compared to patients with the GG genotype. Other genetic and clinical factors may also influence a patient's risk for treatment side effects.", + "phenotypeText": "increased risk for agitation and dysphoria", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444703063", + "literature": [ + "23799451" + ] + }, + { + "genotypeId": "10_94781859_G_G,G", + "isDirectTarget": false, + "drugFromSource": "doxorubicin", + "drugId": "CHEMBL53463", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with GG genotype and breast cancer may have a decreased risk of neutropenia when treated with cyclophosphamide, doxorubicin and fluorouracil (FAC) as compared to patients with the AA or AG genotype. Other genetic and clinical factors may also affect the risk for neutropenia in patients taking FAC chemotherapy.", + "phenotypeText": "decreased risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449718271", + "literature": [ + "29507678" + ] + }, + { + "genotypeId": "10_94781859_G_A,A", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with AA genotype and breast cancer may have an increased risk of neutropenia when treated with cyclophosphamide, doxorubicin and fluorouracil (FAC) as compared to patients with the GG genotype. Other genetic and clinical factors may also affect the risk for neutropenia in patients taking FAC chemotherapy.", + "phenotypeText": "increased risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449718271", + "literature": [ + "29507678" + ] + }, + { + "genotypeId": "10_94781859_G_A,A", + "isDirectTarget": false, + "drugFromSource": "doxorubicin", + "drugId": "CHEMBL53463", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with AA genotype and breast cancer may have an increased risk of neutropenia when treated with cyclophosphamide, doxorubicin and fluorouracil (FAC) as compared to patients with the GG genotype. Other genetic and clinical factors may also affect the risk for neutropenia in patients taking FAC chemotherapy.", + "phenotypeText": "increased risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449718271", + "literature": [ + "29507678" + ] + }, + { + "genotypeId": "10_94781859_G_G,G", + "isDirectTarget": false, + "drugFromSource": "doxorubicin", + "drugId": "CHEMBL53463", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the GG genotype and Breast Cancer who are treated with cyclophosphamide and doxorubicin may have a decreased risk of poorer outcome as compared to patients with the AA genotype. Other genetic and clinical factors may also influence a patient's response to treatment.", + "phenotypeText": "decreased risk of poorer outcome", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981202551", + "literature": [ + "20179710", + "29938344" + ] + }, + { + "genotypeId": "10_94781859_G_A,A", + "isDirectTarget": false, + "drugFromSource": "etravirine", + "drugId": "CHEMBL308954", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AA genotype who are treated with etravirine may have a decreased etravirine clearance as compared to patients with the GG genotype. Other genetic and clinical factors may also influence a patient's etravirine clearance.", + "phenotypeText": "decreased etravirine clearance", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444703076", + "literature": [ + "23111422" + ] + }, + { + "genotypeId": "10_94781859_G_G,G", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the GG genotype and Breast Cancer who are treated with cyclophosphamide and doxorubicin may have a decreased risk of poorer outcome as compared to patients with the AA genotype. Other genetic and clinical factors may also influence a patient's response to treatment.", + "phenotypeText": "decreased risk of poorer outcome", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981202551", + "literature": [ + "20179710", + "29938344" + ] + }, + { + "genotypeId": "10_94781859_G_A,A", + "isDirectTarget": false, + "drugFromSource": "nelfinavir", + "drugId": "CHEMBL584", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AA genotype and pancreatic cancer or HIV may have decreased metabolism and increased concentrations of nelfinavir as compared to patients with the GG genotype. Other genetic and clinical factors may also influence metabolism and concentration of nelfinavir.", + "phenotypeText": "decreased metabolism and increased concentrations of nelfinavir", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1447962874", + "literature": [ + "16267764", + "25752914", + "25752914" + ] + }, + { + "genotypeId": "10_94781859_G_G,G", + "isDirectTarget": false, + "drugFromSource": "etravirine", + "drugId": "CHEMBL308954", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the GG genotype who are treated with etravirine may have an increased etravirine clearance as compared to patients with the AG or AA genotype. Other genetic and clinical factors may also influence a patient's etravirine clearance.", + "phenotypeText": "increased etravirine clearance", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444703076", + "literature": [ + "23111422" + ] + }, + { + "genotypeId": "10_94781859_G_A,G", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AG genotype and Systemic Lupus Erythematosus who are treated with cyclophosphamide may have decreased metabolism of cyclophosphamide, leading to lower concentrations of the active metabolite, and a decreased risk of toxicity (ovarian, gastrointestinal, or hematological) as compared to patients with the GG genotype. Other genetic and clinical factors may also influence a patient's risk for cyclophosphamide-induced toxicity.", + "phenotypeText": "decreased risk of toxicity", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981202562", + "literature": [ + "26456622", + "26456622", + "20358205" + ] + }, + { + "genotypeId": "10_94781859_G_G,G", + "isDirectTarget": false, + "drugFromSource": "nelfinavir", + "drugId": "CHEMBL584", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the GG genotype and pancreatic cancer or HIV may have increased metabolism and decreased concentrations of nelfinavir as compared to patients with the AA or AG genotype. Other genetic and clinical factors may also influence metabolism and concentration of nelfinavir.", + "phenotypeText": "decreased concentrations of nelfinavir", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1447962874", + "literature": [ + "16267764", + "25752914", + "25752914" + ] + }, + { + "genotypeId": "10_94781859_G_A,A", + "isDirectTarget": false, + "drugFromSource": "prasugrel", + "drugId": "CHEMBL1201772", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AA genotype who are treated with prasugrel may have a higher rate of high on-treatment platelet reactivity at 1 month of treatment as compared to patients with the GG genotype. However, contradictory findings are reported. Other genetic and clinical factors may also influence a patient's response to prasugrel.", + "phenotypeText": "higher rate of high on-treatment platelet reactivity", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "982040598", + "literature": [ + "23257377", + "23257377", + "17900275", + "17900275" + ] + }, + { + "genotypeId": "10_94781859_G_A,A", + "isDirectTarget": false, + "drugFromSource": "venlafaxine", + "drugId": "CHEMBL637", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AA genotype were not studied. Other genetic and clinical factors may also influence a patient's risk for treatment side effects.", + "phenotypeText": "not studied", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444703063", + "literature": [ + "23799451" + ] + }, + { + "genotypeId": "10_94781859_G_G,G", + "isDirectTarget": false, + "drugFromSource": "prasugrel", + "drugId": "CHEMBL1201772", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the GG genotype who are treated with prasugrel may have a lower rate of high on-treatment platelet reactivity at 1 month of treatment as compared to patients with the AG or AA genotype. However, contradictory findings are reported. Other genetic and clinical factors may also influence a patient's response to prasugrel.", + "phenotypeText": "lower rate of high on-treatment platelet reactivity", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "982040598", + "literature": [ + "23257377", + "23257377", + "17900275", + "17900275" + ] + }, + { + "genotypeId": "10_94781859_G_G,G", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with GG genotype and breast cancer may have a decreased risk of neutropenia when treated with cyclophosphamide, doxorubicin and fluorouracil (FAC) as compared to patients with the AA or AG genotype. Other genetic and clinical factors may also affect the risk for neutropenia in patients taking FAC chemotherapy.", + "phenotypeText": "decreased risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449718271", + "literature": [ + "29507678" + ] + }, + { + "genotypeId": "10_94781859_G_G,G", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the GG genotype and Systemic Lupus Erythematosus who are treated with cyclophosphamide may have increased metabolism of cyclophosphamide, leading to higher concentrations of the active metabolite and an increased risk of toxicity (ovarian, gastrointestinal, or hematological) as compared to patients with the AA and AG genotype. Other genetic and clinical factors may also influence a patient's risk for cyclophosphamide-induced toxicity.", + "phenotypeText": "increased risk of toxicity", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981202562", + "literature": [ + "26456622", + "26456622", + "20358205" + ] + }, + { + "genotypeId": "10_94781859_G_A,A", + "isDirectTarget": false, + "drugFromSource": "doxorubicin", + "drugId": "CHEMBL53463", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AA genotype and Breast Cancer who are treated with cyclophosphamide and doxorubicin may have an increased risk of poorer outcome as compared to patients with the GG genotype. Other genetic and clinical factors may also influence a patient's response to treatment.", + "phenotypeText": "increased risk of poorer outcome", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981202551", + "literature": [ + "20179710", + "29938344" + ] + }, + { + "genotypeId": "10_94781859_G_G,G", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with GG genotype and breast cancer may have a decreased risk of neutropenia when treated with cyclophosphamide, doxorubicin and fluorouracil (FAC) as compared to patients with the AA or AG genotype. Other genetic and clinical factors may also affect the risk for neutropenia in patients taking FAC chemotherapy.", + "phenotypeText": "decreased risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449718271", + "literature": [ + "29507678" + ] + }, + { + "genotypeId": "10_94781859_G_A,G", + "isDirectTarget": false, + "drugFromSource": "etravirine", + "drugId": "CHEMBL308954", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AG genotype who are treated with etravirine may have a decreased etravirine clearance as compared to patients with the GG genotype. Other genetic and clinical factors may also influence a patient's etravirine clearance.", + "phenotypeText": "decreased etravirine clearance", + "pgxCategory": "metabolism/pk", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1444703076", + "literature": [ + "23111422" + ] + }, + { + "genotypeId": "10_94781859_G_A,G", + "isDirectTarget": false, + "drugFromSource": "doxorubicin", + "drugId": "CHEMBL53463", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with AG genotype and breast cancer may have an increased risk of neutropenia when treated with cyclophosphamide, doxorubicin and fluorouracil (FAC) as compared to patients with the GG genotype. Other genetic and clinical factors may also affect the risk for neutropenia in patients taking FAC chemotherapy.", + "phenotypeText": "increased risk of neutropenia", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "1449718271", + "literature": [ + "29507678" + ] + }, + { + "genotypeId": "10_94781859_G_A,A", + "isDirectTarget": false, + "drugFromSource": "cyclophosphamide", + "drugId": "CHEMBL88", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AA genotype and Breast Cancer who are treated with cyclophosphamide and doxorubicin may have an increased risk of poorer outcome as compared to patients with the GG genotype. Other genetic and clinical factors may also influence a patient's response to treatment.", + "phenotypeText": "increased risk of poorer outcome", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981202551", + "literature": [ + "20179710", + "29938344" + ] + }, + { + "genotypeId": "10_94781859_G_A,G", + "isDirectTarget": false, + "drugFromSource": "doxorubicin", + "drugId": "CHEMBL53463", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the AG genotype and Breast Cancer who are treated with cyclophosphamide and doxorubicin may have a decreased risk of poorer outcome as compared to patients with the AA genotype. Other genetic and clinical factors may also influence a patient's response to treatment.", + "phenotypeText": "decreased risk of poorer outcome", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "981202551", + "literature": [ + "20179710", + "29938344" + ] + }, + { + "genotypeId": "1_97082391_T_T,T", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "The A allele of this variant, when measured on plus chromosomal strand, is assigned decreased function by CPIC. Patients with the TT genotype and cancer who are treated with fluorouracil, a fluoropyrimidine-based chemotherapy, may have decreased, but not absent, risk and reduced severity of drug toxicity as compared to patients with the AA or AT genotypes. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of drug toxicity.", + "phenotypeText": "decreased, but not absent, risk and reduced severity of drug toxicity", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981203618", + "literature": [ + "23603345", + "17700593", + "17121937", + "23930673", + "24167597", + "25381393", + "30114658", + "26099996", + "26794347", + "24923815", + "19795123", + "11156223", + "19104657", + "18299612", + "20819423", + "21498394", + "23736036", + "26603945", + "28427087", + "29065426", + "27122156", + "30858516", + "30485432" + ] + }, + { + "genotypeId": "1_97082391_T_A,A", + "isDirectTarget": false, + "drugFromSource": "tegafur", + "drugId": "CHEMBL20883", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs67376798 AA genotype and cancer who are treated with tegafur, a fluoropyrimidine, may have an increased risk of drug toxicity as compared to patients with the TT genotype. This drug-variant pair has been assigned a “no recommendation” by CPIC, as it was determined to be not clinically actionable. Other genetic and clinical factors may also influence response to fluoropyrimidine-based chemotherapy.", + "phenotypeText": "increased risk of drug toxicity", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451266120", + "literature": [ + "21410976", + "23930673", + "26603945" + ] + }, + { + "genotypeId": "1_97082391_T_T,T", + "isDirectTarget": false, + "drugFromSource": "tegafur", + "drugId": "CHEMBL20883", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs67376798 TT genotype and cancer who are treated with tegafur, a fluoropyrimidine, may have a decreased, but not absent, risk of drug toxicity as compared to patients with the AT or AA genotype. This drug-variant pair has been assigned a “no recommendation” by CPIC, as it was determined to be not clinically actionable. Other genetic and clinical factors may also influence response to fluoropyrimidine-based chemotherapy.", + "phenotypeText": "decreased risk of drug toxicity", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451266120", + "literature": [ + "21410976", + "23930673", + "26603945" + ] + }, + { + "genotypeId": "1_97082391_T_T,T", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "The A allele of this variant, when measured on plus chromosomal strand, is assigned decreased function by CPIC. Patients with the TT genotype may have increased activity of DPYD as compared to patients with the AT or AA genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence catalytic activity of DPYD.", + "phenotypeText": "increased activity of DPYD", + "pgxCategory": "other", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451274045", + "literature": [ + "16115930", + "17064846", + "31745289", + "24648345", + "26804652", + "26265035", + "26804652", + "23588312", + "26216193", + "11988088", + "25410891", + "28295243" + ] + }, + { + "genotypeId": "1_97082391_T_A,T", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "The A allele of this variant, when measured on plus chromosomal strand, is assigned decreased function by CPIC. Patients with the AT genotype may have decreased activity of DPYD as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence catalytic activity of DPYD.", + "phenotypeText": "decreased activity of DPYD", + "pgxCategory": "other", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451274045", + "literature": [ + "16115930", + "17064846", + "31745289", + "24648345", + "26804652", + "26265035", + "26804652", + "23588312", + "26216193", + "11988088", + "25410891", + "28295243" + ] + }, + { + "genotypeId": "1_97082391_T_A,A", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "The A allele of this variant, when measured on plus chromosomal strand, is assigned decreased function by CPIC. Patients with the AA genotype may have decreased activity of DPYD as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence catalytic activity of DPYD.", + "phenotypeText": "decreased activity of DPYD", + "pgxCategory": "other", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451274045", + "literature": [ + "16115930", + "17064846", + "31745289", + "24648345", + "26804652", + "26265035", + "26804652", + "23588312", + "26216193", + "11988088", + "25410891", + "28295243" + ] + }, + { + "genotypeId": "1_97082391_T_A,T", + "isDirectTarget": false, + "drugFromSource": "capecitabine", + "drugId": "CHEMBL1773", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "The A allele of rs67376798, when measured on plus chromosomal strand, is assigned decreased function by CPIC. Patients with the AT genotype and cancer who are treated with capecitabine, a fluoropyrimidine-based chemotherapy, may have increased risk and increased severity of drug toxicity as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of drug toxicity.", + "phenotypeText": "increased risk and increased severity of drug toxicity", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451274090", + "literature": [ + "31486738", + "23603345", + "23930673", + "24590654", + "24167597", + "30114658", + "26099996", + "24923815", + "19795123", + "19104657", + "20819423", + "21498394", + "23736036", + "24647007", + "25677447", + "21077799", + "26603945", + "27995989", + "27454530", + "28481884", + "28427087", + "29065426", + "29889674", + "29846282", + "29998006", + "30723313", + "30858516", + "30485432" + ] + }, + { + "genotypeId": "1_97082391_T_A,T", + "isDirectTarget": false, + "drugFromSource": "tegafur", + "drugId": "CHEMBL20883", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with the rs67376798 AT genotype and cancer who are treated with tegafur, a fluoropyrimidine, may have an increased risk of drug toxicity as compared to patients with the TT genotype. This drug-variant pair has been assigned a “no recommendation” by CPIC, as it was determined to be not clinically actionable. Other genetic and clinical factors may also influence response to fluoropyrimidine-based chemotherapy.", + "phenotypeText": "increased risk of drug toxicity", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451266120", + "literature": [ + "21410976", + "23930673", + "26603945" + ] + }, + { + "genotypeId": "1_97082391_T_A,T", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "The A allele of this variant, when measured on plus chromosomal strand, is assigned decreased function by CPIC. Patients with the AT genotype and cancer who are treated with fluorouracil, a fluoropyrimidine-based chemotherapy, may have increased risk and increased severity of drug toxicity as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of drug toxicity.", + "phenotypeText": "increased risk and increased severity of drug toxicity", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981203618", + "literature": [ + "23603345", + "17700593", + "17121937", + "23930673", + "24167597", + "25381393", + "30114658", + "26099996", + "26794347", + "24923815", + "19795123", + "11156223", + "19104657", + "18299612", + "20819423", + "21498394", + "23736036", + "26603945", + "28427087", + "29065426", + "27122156", + "30858516", + "30485432" + ] + }, + { + "genotypeId": "1_97082391_T_A,A", + "isDirectTarget": false, + "drugFromSource": "fluorouracil", + "drugId": "CHEMBL185", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "The A allele of this variant, when measured on plus chromosomal strand, is assigned decreased function by CPIC. Patients with the AA genotype and cancer who are treated with fluorouracil, a fluoropyrimidine-based chemotherapy, may have increased risk and increased severity of drug toxicity as compared to patients with the TT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of drug toxicity.", + "phenotypeText": "increased risk and increased severity of drug toxicity", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "981203618", + "literature": [ + "23603345", + "17700593", + "17121937", + "23930673", + "24167597", + "25381393", + "30114658", + "26099996", + "26794347", + "24923815", + "19795123", + "11156223", + "19104657", + "18299612", + "20819423", + "21498394", + "23736036", + "26603945", + "28427087", + "29065426", + "27122156", + "30858516", + "30485432" + ] + }, + { + "genotypeId": "1_97082391_T_T,T", + "isDirectTarget": false, + "drugFromSource": "capecitabine", + "drugId": "CHEMBL1773", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "The A allele of rs67376798, when measured on plus chromosomal strand, is assigned decreased function by CPIC. Patients with the TT genotype and cancer who are treated with capecitabine, a fluoropyrimidine-based chemotherapy, may have decreased, but not absent, risk and reduced severity of drug toxicity as compared to patients with the AA or AT genotype. However, conflicting evidence has been reported. Other genetic and clinical factors may also influence risk of drug toxicity.", + "phenotypeText": "decreased, but not absent, risk and reduced severity of drug toxicity", + "pgxCategory": "toxicity", + "evidenceLevel": "1A", + "datasourceId": "pharmgkb", + "studyId": "1451274090", + "literature": [ + "31486738", + "23603345", + "23930673", + "24590654", + "24167597", + "30114658", + "26099996", + "24923815", + "19795123", + "19104657", + "20819423", + "21498394", + "23736036", + "24647007", + "25677447", + "21077799", + "26603945", + "27995989", + "27454530", + "28481884", + "28427087", + "29065426", + "29889674", + "29846282", + "29998006", + "30723313", + "30858516", + "30485432" + ] + }, + { + "genotypeId": "22_42128945_C_C,C", + "isDirectTarget": false, + "drugFromSource": "metoprolol", + "drugId": "CHEMBL13", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with CC genotype may have lower plasma concentrations of metoprolol and have smaller reductions in heart rate, diastolic blood pressure, and mean arterial pressure when treated with metoprolol as compared to patients with the TT genotype. Other genetic and clinical factors may also influence a patient's response to metoprolol. Please check other variants for PM phenotype.", + "phenotypeText": "lower plasma concentrations of metoprolol and smaller reductions in heart rate, diastolic blood pressure, and mean arterial pressure", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655385352", + "literature": [ + "19037197" + ] + }, + { + "genotypeId": "22_42128945_C_T,T", + "isDirectTarget": false, + "drugFromSource": "metoprolol", + "drugId": "CHEMBL13", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with TT genotype may have higher plasma concentrations of metoprolol and have greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure when treated with metoprolol as compared to patients with CC genotype. Other genetic and clinical factors may also influence a patient's response to metoprolol. Please check other variants for PM phenotype.", + "phenotypeText": "higher plasma concentrations of metoprolol and greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655385352", + "literature": [ + "19037197" + ] + }, + { + "genotypeId": "22_42128945_C_C,T", + "isDirectTarget": false, + "drugFromSource": "metoprolol", + "drugId": "CHEMBL13", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Patients with CT genotype may have higher plasma concentrations of metoprolol and have greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure when treated with metoprolol as compared to patients with the CC genotype. Other genetic and clinical factors may also influence a patient's response to metoprolol. Please check other variants for PM phenotype.", + "phenotypeText": "higher plasma concentrations of metoprolol and greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure", + "pgxCategory": "efficacy", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655385352", + "literature": [ + "19037197" + ] + }, + { + "genotypeId": "6_18138997_C_C,T", + "isDirectTarget": false, + "drugFromSource": "cisplatin", + "drugId": "CHEMBL2068237", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Children with the CT genotype and cancer who are treated with cisplatin may have an increased risk for hearing loss as compared to children with the CC genotype. However, multiple studies have found no association between this SNP and risk of cisplatin-induced ototoxicity. Other genetic and clinical factors may also influence a patient's risk for hearing loss with cisplatin treatment.", + "phenotypeText": "increased risk for hearing loss", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655386597", + "literature": [ + "23588304", + "23820299", + "19898482", + "25141953", + "25551397", + "28448657" + ] + }, + { + "genotypeId": "6_18138997_C_T,T", + "isDirectTarget": false, + "drugFromSource": "cisplatin", + "drugId": "CHEMBL2068237", + "phenotypeFromSourceId": null, + "genotypeAnnotationText": "Children with the TT genotype and cancer who are treated with cisplatin may have an increased risk for hearing loss as compared to children with the CC genotype. However, multiple studies have found no association between this SNP and risk of cisplatin-induced ototoxicity. Other genetic and clinical factors may also influence a patient's risk for hearing loss with cisplatin treatment.", + "phenotypeText": "increased risk for hearing loss", + "pgxCategory": "toxicity", + "evidenceLevel": "3", + "datasourceId": "pharmgkb", + "studyId": "655386597", + "literature": [ + "23588304", + "23820299", + "19898482", + "25141953", + "25551397", + "28448657" + ] + } + ] + } +}`), + }; +} \ No newline at end of file diff --git a/packages/sections/src/variant/Pharmacogenomics/Description.tsx b/packages/sections/src/variant/Pharmacogenomics/Description.tsx new file mode 100644 index 000000000..07d829014 --- /dev/null +++ b/packages/sections/src/variant/Pharmacogenomics/Description.tsx @@ -0,0 +1,19 @@ +import { Link } from "ui"; + +type DescriptionProps = { + variantId: string; +}; + +function Description({ variantId }: DescriptionProps) { + return ( + <> + Genotypes in {variantId} known to affect drug response. Source:{" "} + + PharmGKB + + . + + ); +} + +export default Description; \ No newline at end of file diff --git a/packages/sections/src/variant/Pharmacogenomics/PharmacogenomicsTable.tsx b/packages/sections/src/variant/Pharmacogenomics/PharmacogenomicsTable.tsx new file mode 100644 index 000000000..74da3e23f --- /dev/null +++ b/packages/sections/src/variant/Pharmacogenomics/PharmacogenomicsTable.tsx @@ -0,0 +1,200 @@ +import classNames from "classnames"; +import { makeStyles } from "@mui/styles"; +import { Link, DataTable, Tooltip, LabelChip, PublicationsDrawer } from "ui"; + +import { epmcUrl } from "../../utils/urls"; +import { + defaultRowsPerPageOptions, + naLabel, + PHARM_GKB_COLOR, + variantConsequenceSource, +} from "../../constants"; +import { identifiersOrgLink, sentenceCase } from "../../utils/global"; +import { FontAwesomeIcon } from "@fortawesome/react-fontawesome"; +import { faCircleCheck } from "@fortawesome/free-solid-svg-icons"; +import { faCircleXmark } from "@fortawesome/free-regular-svg-icons"; + +const useStyles = makeStyles(theme => ({ + level: { + color: "white", + padding: theme.spacing(0.5), + borderRadius: theme.spacing(0.5), + }, + green: { + background: PHARM_GKB_COLOR.green, + }, + red: { + background: PHARM_GKB_COLOR.red, + }, + yellow: { + background: PHARM_GKB_COLOR.yellow, + }, + blue: { + background: theme.palette.primary.main, + }, + blueIcon: { + color: theme.palette.primary.main, + }, +})); + +const getLevelElementClassName = level => { + switch (level) { + case "1": + return "green"; + case "1A": + return "green"; + case "1B": + return "green"; + case "2": + return "blue"; + case "2A": + return "blue"; + case "2B": + return "blue"; + case "3": + return "yellow"; + case "4": + return "red"; + default: + return "red"; + } +}; + +function OverviewTab({ pharmacogenomics, query, variables }) { + const classes = useStyles(); + const columns = [ + { + id: "genotypeId", + label: "Genotype ID", + tooltip: ( + <> + VCF-style(chr_pos_ref_allele1,allele2). See{" "} + + here + {" "} + for more details. + + ), + renderCell: ({ genotypeId }) => genotypeId || naLabel, + }, + { + id: "drug", + label: "Drug(s)", + renderCell: ({ drugId, drugFromSource }) => { + let drugElement = drugFromSource || drugId || naLabel; + if (drugId) drugElement = {drugElement}; + return drugElement; + }, + filterValue: ({ drugId, drugFromSource }) => `${drugFromSource} ${drugId}`, + }, + { + id: "drugResponse", + label: "Drug Response Phenotype", + renderCell: ({ phenotypeText = naLabel, phenotypeFromSourceId, genotypeAnnotationText }) => { + let phenotypeTextElement = phenotypeText; + if (phenotypeFromSourceId) + phenotypeTextElement = ( + {phenotypeTextElement} + ); + if (genotypeAnnotationText) + phenotypeTextElement = ( + + {phenotypeTextElement} + + ); + return phenotypeTextElement; + }, + filterValue: ({ phenotypeText }) => `${phenotypeText}`, + }, + { + id: "drugResponseCategory", + label: "Drug Response Category", + renderCell: ({ pgxCategory }) => pgxCategory || naLabel, + filterValue: ({ pgxCategory }) => pgxCategory, + }, + { + id: "isDirectTarget", + label: "Direct Drug Target", + renderCell: ({ isDirectTarget }) => { + const ICON_NAME = isDirectTarget ? faCircleCheck : faCircleXmark; + return ; + }, + }, + { + id: "confidenceLevel", + label: "Confidence Level", + comparator: (a, b) => (b.evidenceLevel < a.evidenceLevel ? 1 : -1), + sortable: true, + tooltip: ( + <> + As defined by + + {" "} + PharmGKB ClinAnn Levels + + + ), + renderCell: ({ evidenceLevel }) => { + if (evidenceLevel) { + const levelClass = getLevelElementClassName(evidenceLevel); + return ( + + Level {evidenceLevel} + + ); + } + return naLabel; + }, + filterValue: ({ evidenceLevel }) => `Level ${evidenceLevel}`, + }, + { + id: "source", + label: "Source", + renderCell: ({ studyId }) => + studyId ? ( + + PharmGKB + + ) : ( + naLabel + ), + }, + { + id: "literature", + renderCell: ({ literature }) => { + const literatureList = + literature?.reduce((acc, id) => { + if (id === "NA") return acc; + + return [ + ...acc, + { + name: id, + url: epmcUrl(id), + group: "literature", + }, + ]; + }, []) || []; + + return ; + }, + }, + ]; + return ( + + ); +} + +export default OverviewTab; \ No newline at end of file diff --git a/packages/sections/src/variant/Pharmacogenomics/Summary.tsx b/packages/sections/src/variant/Pharmacogenomics/Summary.tsx new file mode 100644 index 000000000..9797f8ef3 --- /dev/null +++ b/packages/sections/src/variant/Pharmacogenomics/Summary.tsx @@ -0,0 +1,33 @@ +import { SummaryItem, usePlatformApi } from "ui"; + +import { definition } from "."; +// import PHARMACOGENOMICS_SUMMARY_FRAGMENT from "./PharmacogenomicsSummary.gql"; + +function Summary() { + // const request = usePlatformApi(PHARMACOGENOMICS_SUMMARY_FRAGMENT); + + // !! USE PLACEHOLDER REQUEST FOR NOW !! + // const request = usePlatformApi(EVA_SUMMARY); + const request = { + loading: false, + error: undefined, + data: true, // data is not actually used by summary - only cares if there is data + }; + + return ( + {}} // !! renderSummary PROP NOT USED ANYMORE ANYWAY? + // renderSummary={({ pharmacogenomics }) => + // `${pharmacogenomics.length} Pharmacogenomics Records` + // } + /> + ); +} + +// Summary.fragments = { +// PharmacogenomicsSummaryFragment: PHARMACOGENOMICS_SUMMARY_FRAGMENT, +// }; + +export default Summary; diff --git a/packages/sections/src/variant/Pharmacogenomics/index.ts b/packages/sections/src/variant/Pharmacogenomics/index.ts new file mode 100644 index 000000000..cb7d51abf --- /dev/null +++ b/packages/sections/src/variant/Pharmacogenomics/index.ts @@ -0,0 +1,7 @@ +export const definition = { + id: "pharmacogenetics", + name: "Pharmacogenetics", + shortName: "PGx", + hasData: () => true, // !! CHANGE WHEN USE GQL !! + // hasData: data => data.pharmacogenomics.length > 0, +}; From 4e6c412e32351caa05e460149f89e9219eddf303 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Mon, 10 Jun 2024 17:22:08 +0100 Subject: [PATCH 04/17] move reported protein link to description (#381) --- .../src/variant/UniProtVariants/Body.tsx | 17 ++--------------- .../src/variant/UniProtVariants/Description.tsx | 6 ++++-- 2 files changed, 6 insertions(+), 17 deletions(-) diff --git a/packages/sections/src/variant/UniProtVariants/Body.tsx b/packages/sections/src/variant/UniProtVariants/Body.tsx index 103e99baf..1d22e33a1 100644 --- a/packages/sections/src/variant/UniProtVariants/Body.tsx +++ b/packages/sections/src/variant/UniProtVariants/Body.tsx @@ -4,22 +4,12 @@ import { Link, SectionItem, Tooltip, PublicationsDrawer, DataTable } from "ui"; import { definition } from "../../variant/UniProtVariants"; import Description from "../../variant/UniProtVariants/Description"; import { epmcUrl } from "../../utils/urls"; -import { identifiersOrgLink } from "../../utils/global"; import { defaultRowsPerPageOptions, sectionsBaseSizeQuery, } from "../../constants"; // import UNIPROT_VARIANTS_QUERY from "./UniprotVariantsQuery.gql"; function getColumns(label: string) { return [ - { - id: "targetFromSourceId", - label: "Reported protein", - renderCell: ({ targetFromSourceId }) => ( - - {targetFromSourceId} - - ), - }, { id: "disease.name", label: "Disease/phenotype", @@ -81,9 +71,6 @@ type BodyProps = { export function Body({ id, label, entity }) { - // ID IS JUST THE VARIANT ID STRING FOR NOW - // const { ensgId, efoId } = id; - // const variables = { // ensemblId: ensgId, // efoId, @@ -102,8 +89,8 @@ export function Body({ id, label, entity }) { definition={definition} request={request} entity={entity} - renderDescription={() => } - renderBody={({ disease }) => { + renderDescription={data => } + renderBody={() => { // const { rows } = disease.uniprotVariantsSummary; const rows = request.data.variant.uniProtVariants; return ( diff --git a/packages/sections/src/variant/UniProtVariants/Description.tsx b/packages/sections/src/variant/UniProtVariants/Description.tsx index 5f5ecf471..1b2900326 100644 --- a/packages/sections/src/variant/UniProtVariants/Description.tsx +++ b/packages/sections/src/variant/UniProtVariants/Description.tsx @@ -1,14 +1,16 @@ import { Link } from "ui"; +import { identifiersOrgLink } from "../../utils/global"; type DescriptionProps = { variantId: string; + data: any; }; -function Description({ variantId }: DescriptionProps) { +function Description({ variantId, data }: DescriptionProps) { return ( <> Literature-based curation associating {variantId}{" "} to a disease/phenotype. Source:{" "} - + UniProt From 517da05d85e9ad208db5df0c4ce14e664a7029e3 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Wed, 19 Jun 2024 13:39:16 +0100 Subject: [PATCH 05/17] [Platform] Add GWAS credible sets widget to variant page (#390) --- .../src/pages/VariantPage/Profile.tsx | 5 + apps/platform/src/pages/VariantPage/types.ts | 43 + .../src/variant/GWASCredibleSets/Body.tsx | 1534 +++++++++++++++++ .../variant/GWASCredibleSets/Description.tsx | 18 + .../src/variant/GWASCredibleSets/Summary.tsx | 31 + .../src/variant/GWASCredibleSets/index.ts | 14 + 6 files changed, 1645 insertions(+) create mode 100644 packages/sections/src/variant/GWASCredibleSets/Body.tsx create mode 100644 packages/sections/src/variant/GWASCredibleSets/Description.tsx create mode 100644 packages/sections/src/variant/GWASCredibleSets/Summary.tsx create mode 100644 packages/sections/src/variant/GWASCredibleSets/index.ts diff --git a/apps/platform/src/pages/VariantPage/Profile.tsx b/apps/platform/src/pages/VariantPage/Profile.tsx index b362393dd..471fb0c04 100644 --- a/apps/platform/src/pages/VariantPage/Profile.tsx +++ b/apps/platform/src/pages/VariantPage/Profile.tsx @@ -9,6 +9,7 @@ import { import InSilicoPredictorsSummary from "sections/src/variant/InSilicoPredictors/Summary"; import EVASummary from "sections/src/variant/EVA/Summary"; import UniProtVariantsSummary from "sections/src/variant/UniProtVariants/Summary"; +import GWASCredibleSetsSummary from "sections/src/variant/GWASCredibleSets/Summary"; import PharmacogenomicsSummary from "sections/src/variant/Pharmacogenomics/Summary"; import ProfileHeader from "./ProfileHeader"; @@ -16,12 +17,14 @@ import ProfileHeader from "./ProfileHeader"; const InSilicoPredictorsSection = lazy(() => import("sections/src/variant/InSilicoPredictors/Body")); const EVASection = lazy(() => import("sections/src/variant/EVA/Body")); const UniProtVariantsSection = lazy(() => import("sections/src/variant/UniProtVariants/Body")); +const GWASCredibleSetsSection = lazy(() => import("sections/src/variant/GWASCredibleSets/Body")); const PharmacogenomicsSection = lazy(() => import("sections/src/variant/Pharmacogenomics/Body")); const summaries = [ InSilicoPredictorsSummary, EVASummary, UniProtVariantsSummary, + GWASCredibleSetsSummary, PharmacogenomicsSummary, ]; @@ -51,6 +54,7 @@ function Profile({ varId }: ProfileProps) { + @@ -65,6 +69,7 @@ function Profile({ varId }: ProfileProps) { }> + {/* NEED ANYTHING IN ???? see evidence page */} diff --git a/apps/platform/src/pages/VariantPage/types.ts b/apps/platform/src/pages/VariantPage/types.ts index 9c3975e2a..e0c87f872 100644 --- a/apps/platform/src/pages/VariantPage/types.ts +++ b/apps/platform/src/pages/VariantPage/types.ts @@ -94,6 +94,49 @@ export type UniProtVariantsType = { "target.approvedSymbol": string, "disease.id": string, "disease.name": string, +}; + +// ================== +// GWAS Credible Sets +// ================== + +export type GWASCredibleSets = { + variantId: string, + study: { + id: string, + traitFromSource: string, + disease: { + id: string, + name: string, + } + }, + pValueMantissa: number, + pValueExponent: number, + beta: number, + ldPopulationStructure: [ + { + ldPopulation: string, + relativeSampleSize: number, + } + ], + finemappingMethod: string, + l2g: { + score: string, + target: { + id: string, + approvedSymbol: string, + } + }, + locus: [ + { + variantId: string, + r2Overall: number, + posteriorProbability: number, + standardError: number, + is95CredibleSet: boolean, + is99CredibleSet: boolean, + } + ] }; // ================ diff --git a/packages/sections/src/variant/GWASCredibleSets/Body.tsx b/packages/sections/src/variant/GWASCredibleSets/Body.tsx new file mode 100644 index 000000000..20235fc0a --- /dev/null +++ b/packages/sections/src/variant/GWASCredibleSets/Body.tsx @@ -0,0 +1,1534 @@ +import { Link, SectionItem, DataTable, ScientificNotation } from "ui"; +import { Box, Chip } from "@mui/material"; +import { naLabel, defaultRowsPerPageOptions } from "../../constants"; +import { definition } from "."; +import Description from "./Description"; + +function getColumns(id: string, label: string) { + + return [ + { + id: "leadVariant", + label: "Lead Variant", + renderCell: ({ variantId }) => ( + variantId === id + ? + {variantId} + + + : {variantId} + ), + exportLabel: "Lead Variant", + }, + { + id: "trait", + label: "Trait", + renderCell: d => ( + + {d["study.disease.name"]} + + ), + exportLabel: "Trait", + }, + { + id: "study", + label: "Study", + renderCell: d => ( + + {d["study.id"]} + + ), + exportLabel: "Study", + }, + { + id: "pValue", + label: "P-Value", + comparator: (a, b) => + a.pValueMantissa * 10 ** a.pValueExponent - b.pValueMantissa * 10 ** b.pValueExponent, + sortable: true, + renderCell: d => ( + + ), + exportLabel: "P-Value", + }, + { + id: "beta", + label: "Beta", + tooltip: "Beta with respect to the ALT allele", + renderCell: ({ beta }) => beta || beta === 0 ? beta.toPrecision(3) : naLabel, + exportLabel: "Beta", + }, + // { + // id: "ldr2", + // label: "LD (r2)", + // tooltip: "Linkage disequilibrium with the queried variant", + // renderCell: ({ locus }) => ( + // locus.find(obj => obj.variantId === id).r2Overall.toFixed(2) + // ), + // exportLabel: "LD (r2)", + // }, + { + id: "fineMappingMethod", + label: "Finemapping Method", + renderCell: ({ finemappingMethod }) => finemappingMethod, + exportLabel: "Finemapping Method", + }, + { + id: "topL2G", + label: "Top L2G", + tooltip: "Top gene prioritised by our locus-to-gene model", + renderCell: d => ( + + {d["l2g.target.approvedSymbol"]} + + ), + exportLabel: "Top L2G", + }, + { + id: "l2gScore", + label: "L2G score", + comparator: (a, b) => a["l2g.score"] - b["l2g.score"], + sortable: true, + renderCell: d => d["l2g.score"].toFixed(3), + exportLabel: "L2G score", + }, + { + id: "credibleSetSize", + label: "Credible Set Size", + comparator: (a, b) => a.locus.length - b.locus.length, + sortable: true, + renderCell: ({ locus }) => locus.length, + exportLabel: "Credible Set Size", + } + ]; +} + +// !!!! LOAD LOCAL DATA FOR NOW +// const [metadata, setMetadata] = +// useState("waiting"); +const request = mockQuery(); + +type BodyProps = { + id: string, + label: string, + entity: string, +}; + +// !! FOR NOW, RENAME id AND SET IT MANUALLY BELOW +function Body({ id: doNotUseForNow, label, entity }: BodyProps) { + + // !! FOR NOW, SET id (IE THE PAGE VARIANT ID) TO FAKE TAG_VARIANT_ID + const id = request.data.TAG_VARIANT_ID; + + const columns = getColumns(id, label); + const rows = request.data.variant.gwasCredibleSets; + + return ( + } + renderBody={() => ( + + )} + /> + ); + +} + +export default Body; + +function mockQuery() { + return { + loading: false, + error: undefined, + data: JSON.parse(` +{ + "TAG_VARIANT_ID": "10_100315722_G_A", + "variant": { + "gwasCredibleSets": [ + { + "variantId": "2_11594935_C_A", + "study.id": "FINNGEN_R10_N14_ENDOMETRIOSIS_OVARY", + "study.traitFromSource": "Endometriosis of ovary", + "study.disease.id": "EFO_1000418", + "study.disease.traitFromSource": "Endometriosis of ovary", + "pValueMantissa": 2.164, + "pValueExponent": -14, + "beta": -0.145978, + "posteriorProbability": 0.111228299502257, + "ldPopulationStructure": [ + { + "ldPopulation": "fin", + "relativeSampleSize": 1.0 + } + ], + "finemappingMethod": "SuSie", + "l2g.score": 0.9417305588722228, + "l2g.target.id": "ENSG00000196208", + "l2g.target.approvedSymbol": "GREB1", + "locus": [ + { + "variantId": "2_11593419_A_AACTC", + "posteriorProbability": 0.177326488791841, + "logBF": 27.5495298288152, + "pValueMantissa": 1.319, + "pValueExponent": -14, + "beta": -0.146968, + "standardError": 0.0190768, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11593362_G_T", + "posteriorProbability": 0.176010722376543, + "logBF": 27.5420821417015, + "pValueMantissa": 1.326, + "pValueExponent": -14, + "beta": -0.146956, + "standardError": 0.019077, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11592421_G_GAATCAC", + "posteriorProbability": 0.130911954682145, + "logBF": 27.2460622215016, + "pValueMantissa": 1.791, + "pValueExponent": -14, + "beta": -0.146099, + "standardError": 0.0190611, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11588262_T_C", + "posteriorProbability": 0.13027211244461, + "logBF": 27.2411626613978, + "pValueMantissa": 1.788, + "pValueExponent": -14, + "beta": -0.145821, + "standardError": 0.0190242, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11587963_C_T", + "posteriorProbability": 0.129091027085527, + "logBF": 27.2320550177644, + "pValueMantissa": 1.801, + "pValueExponent": -14, + "beta": -0.14579, + "standardError": 0.0190224, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11587954_G_A", + "posteriorProbability": 0.128198289878656, + "logBF": 27.2251154308426, + "pValueMantissa": 1.817, + "pValueExponent": -14, + "beta": -0.145762, + "standardError": 0.0190217, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11594935_C_A", + "posteriorProbability": 0.111228299502257, + "logBF": 27.0831220672907, + "pValueMantissa": 2.164, + "pValueExponent": -14, + "beta": -0.145978, + "standardError": 0.0191058, + "is95CredibleSet": true, + "is99CredibleSet": true + } + ] + }, + { + "variantId": "2_11594935_C_A", + "study.id": "FINNGEN_R10_N14_OTHNONINFUTER", + "study.traitFromSource": "Other noninflammatory disorders of uterus, except cervix", + "study.disease.id": "MONDO_0002654", + "study.disease.traitFromSource": "Other noninflammatory disorders of uterus, except cervix", + "pValueMantissa": 1.26, + "pValueExponent": -9, + "beta": -0.10118, + "posteriorProbability": 0.0646240799797483, + "ldPopulationStructure": [ + { + "ldPopulation": "fin", + "relativeSampleSize": 1.0 + } + ], + "finemappingMethod": "SuSie", + "l2g.score": 0.877708911895752, + "l2g.target.id": "ENSG00000196208", + "l2g.target.approvedSymbol": "GREB1", + "locus": [ + { + "variantId": "2_11583732_G_A", + "posteriorProbability": 0.123874897400711, + "logBF": 16.9354491631014, + "pValueMantissa": 6.594, + "pValueExponent": -10, + "beta": -0.102154, + "standardError": 0.0165417, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11582984_G_A", + "posteriorProbability": 0.104208303192892, + "logBF": 16.7625688099972, + "pValueMantissa": 7.91, + "pValueExponent": -10, + "beta": -0.101712, + "standardError": 0.0165474, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11584454_G_T", + "posteriorProbability": 0.103616217105774, + "logBF": 16.7568708520451, + "pValueMantissa": 7.976, + "pValueExponent": -10, + "beta": -0.10159, + "standardError": 0.016531, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11587963_C_T", + "posteriorProbability": 0.101382972506177, + "logBF": 16.7350821517542, + "pValueMantissa": 7.887, + "pValueExponent": -10, + "beta": -0.102021, + "standardError": 0.0165963, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11587954_G_A", + "posteriorProbability": 0.100033212473414, + "logBF": 16.7216792542811, + "pValueMantissa": 7.997, + "pValueExponent": -10, + "beta": -0.101981, + "standardError": 0.0165958, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11588262_T_C", + "posteriorProbability": 0.098433376267059, + "logBF": 16.7055569349524, + "pValueMantissa": 8.132, + "pValueExponent": -10, + "beta": -0.101949, + "standardError": 0.0165978, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11592421_G_GAATCAC", + "posteriorProbability": 0.0806260576774133, + "logBF": 16.5059988922095, + "pValueMantissa": 1.004, + "pValueExponent": -9, + "beta": -0.101586, + "standardError": 0.0166293, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11593419_A_AACTC", + "posteriorProbability": 0.072037612772621, + "logBF": 16.3933653809327, + "pValueMantissa": 1.128, + "pValueExponent": -9, + "beta": -0.101354, + "standardError": 0.0166421, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11593362_G_T", + "posteriorProbability": 0.0717864382037803, + "logBF": 16.3898725739579, + "pValueMantissa": 1.132, + "pValueExponent": -9, + "beta": -0.101344, + "standardError": 0.0166421, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11594935_C_A", + "posteriorProbability": 0.0646240799797483, + "logBF": 16.2847640951372, + "pValueMantissa": 1.26, + "pValueExponent": -9, + "beta": -0.10118, + "standardError": 0.0166623, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11585115_G_A", + "posteriorProbability": 0.0522970712402089, + "logBF": 16.0731173689718, + "pValueMantissa": 1.633, + "pValueExponent": -9, + "beta": -0.0997497, + "standardError": 0.0165406, + "is95CredibleSet": true, + "is99CredibleSet": true + } + ] + }, + { + "variantId": "2_11594935_C_A", + "study.id": "FINNGEN_R10_N14_ENDOMETRIOSIS_DEEP", + "study.traitFromSource": "Deep endometriosis", + "study.disease.id": "EFO_0001065", + "study.disease.traitFromSource": "Deep endometriosis", + "pValueMantissa": 3.09, + "pValueExponent": -13, + "beta": -0.194547, + "posteriorProbability": 0.192679582087133, + "ldPopulationStructure": [ + { + "ldPopulation": "fin", + "relativeSampleSize": 1.0 + } + ], + "finemappingMethod": "SuSie", + "l2g.score": 0.9246734380722046, + "l2g.target.id": "ENSG00000196208", + "l2g.target.approvedSymbol": "GREB1", + "locus": [ + { + "variantId": "2_11594935_C_A", + "posteriorProbability": 0.192679582087133, + "logBF": 23.2810244386144, + "pValueMantissa": 3.09, + "pValueExponent": -13, + "beta": -0.194547, + "standardError": 0.0266854, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11593419_A_AACTC", + "posteriorProbability": 0.0894204712473743, + "logBF": 22.513345466639, + "pValueMantissa": 6.808, + "pValueExponent": -13, + "beta": -0.191354, + "standardError": 0.026639, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11592421_G_GAATCAC", + "posteriorProbability": 0.0878966747817931, + "logBF": 22.4961578002195, + "pValueMantissa": 6.842, + "pValueExponent": -13, + "beta": -0.191185, + "standardError": 0.0266179, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11593362_G_T", + "posteriorProbability": 0.0878367985233052, + "logBF": 22.4954763562159, + "pValueMantissa": 6.939, + "pValueExponent": -13, + "beta": -0.191285, + "standardError": 0.026639, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11588262_T_C", + "posteriorProbability": 0.0779502392676064, + "logBF": 22.3760664908027, + "pValueMantissa": 7.709, + "pValueExponent": -13, + "beta": -0.190361, + "standardError": 0.0265637, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11587954_G_A", + "posteriorProbability": 0.0774926306363911, + "logBF": 22.370178669078, + "pValueMantissa": 7.754, + "pValueExponent": -13, + "beta": -0.190316, + "standardError": 0.0265603, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11587963_C_T", + "posteriorProbability": 0.0768791505375317, + "logBF": 22.3622305412039, + "pValueMantissa": 7.82, + "pValueExponent": -13, + "beta": -0.190291, + "standardError": 0.0265611, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11581409_T_G", + "posteriorProbability": 0.0685780742815617, + "logBF": 22.2479686925592, + "pValueMantissa": 1.972, + "pValueExponent": -12, + "beta": -0.185412, + "standardError": 0.0263503, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11585115_G_A", + "posteriorProbability": 0.0465175249703967, + "logBF": 21.8598249484779, + "pValueMantissa": 4.316, + "pValueExponent": -12, + "beta": -0.183247, + "standardError": 0.0264562, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11583732_G_A", + "posteriorProbability": 0.0433506043212946, + "logBF": 21.7893164694463, + "pValueMantissa": 4.539, + "pValueExponent": -12, + "beta": -0.182998, + "standardError": 0.0264476, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11582984_G_A", + "posteriorProbability": 0.0283803256702863, + "logBF": 21.3656919728135, + "pValueMantissa": 7.176, + "pValueExponent": -12, + "beta": -0.181343, + "standardError": 0.0264576, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11584454_G_T", + "posteriorProbability": 0.0264305054626867, + "logBF": 21.2945146788173, + "pValueMantissa": 7.7, + "pValueExponent": -12, + "beta": -0.18092, + "standardError": 0.0264348, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11585053_G_GA", + "posteriorProbability": 0.00907895051735062, + "logBF": 20.2259544299461, + "pValueMantissa": 2.465, + "pValueExponent": -11, + "beta": -0.176521, + "standardError": 0.0264433, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11578465_C_T", + "posteriorProbability": 0.00767848475087483, + "logBF": 20.0584180554332, + "pValueMantissa": 2.018, + "pValueExponent": -11, + "beta": 0.177029, + "standardError": 0.0264038, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11584558_A_G", + "posteriorProbability": 0.00643486002428558, + "logBF": 19.8817259143663, + "pValueMantissa": 1.498, + "pValueExponent": -11, + "beta": -0.171297, + "standardError": 0.0253845, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11584349_A_G", + "posteriorProbability": 0.00495008552802085, + "logBF": 19.619400680622, + "pValueMantissa": 1.988, + "pValueExponent": -11, + "beta": -0.170425, + "standardError": 0.0254103, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11594189_T_C", + "posteriorProbability": 0.00461446304263031, + "logBF": 19.5491913365289, + "pValueMantissa": 6.279, + "pValueExponent": -12, + "beta": -0.175345, + "standardError": 0.0255115, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": 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"2_11584349_A_G", + "posteriorProbability": 0.0101171975106718, + "logBF": 11.1326484609819, + "pValueMantissa": 3.535, + "pValueExponent": -7, + "beta": -0.0944569, + "standardError": 0.0185484, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11581409_T_G", + "posteriorProbability": 0.00820041385034962, + "logBF": 10.9225963838481, + "pValueMantissa": 5.027, + "pValueExponent": -7, + "beta": -0.0958947, + "standardError": 0.0190825, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11594935_C_A", + "posteriorProbability": 0.00641158923615498, + "logBF": 10.6765189322568, + "pValueMantissa": 6.786, + "pValueExponent": -7, + "beta": -0.095918, + "standardError": 0.0193095, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11593419_A_AACTC", + "posteriorProbability": 0.0043797563654958, + "logBF": 10.2954048598218, + "pValueMantissa": 9.945, + "pValueExponent": -7, + "beta": -0.0943251, + "standardError": 0.0192787, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11593362_G_T", + "posteriorProbability": 0.00431482605400924, + "logBF": 10.2804687730865, + "pValueMantissa": 1.01, + "pValueExponent": -6, + "beta": -0.0942685, + "standardError": 0.0192791, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11578732_T_C", + "posteriorProbability": 0.0037619461670644, + "logBF": 10.1433481824145, + "pValueMantissa": 9.056, + "pValueExponent": -7, + "beta": 0.0924575, + "standardError": 0.0188262, + "is95CredibleSet": true, + "is99CredibleSet": true + } + ] + }, + { + "variantId": "2_11594935_C_A", + "study.id": "FINNGEN_R10_N14_ENDOMETRIOSIS_ASRM_STAGE3_4", + "study.traitFromSource": "Endomtriosis ASRM stages 3,4", + "study.disease.id": "EFO_0001065", + "study.disease.traitFromSource": "Endomtriosis ASRM stages 3,4", + "pValueMantissa": 1.016, + "pValueExponent": -17, + "beta": -0.142225, + "posteriorProbability": 0.122413904830971, + "ldPopulationStructure": [ + { + "ldPopulation": "fin", + "relativeSampleSize": 1.0 + } + ], + "finemappingMethod": "SuSie", + "l2g.score": 0.8896055221557617, + "l2g.target.id": "ENSG00000196208", + "l2g.target.approvedSymbol": "GREB1", + "locus": [ + { + "variantId": "2_11593419_A_AACTC", + "posteriorProbability": 0.189160147932363, + "logBF": 35.0639884167124, + "pValueMantissa": 6.226, + "pValueExponent": -18, + "beta": -0.142948, + "standardError": 0.0165673, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11593362_G_T", + "posteriorProbability": 0.185721389511439, + "logBF": 35.0456420617663, + "pValueMantissa": 6.339, + "pValueExponent": -18, + "beta": -0.142916, + "standardError": 0.0165675, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11594935_C_A", + "posteriorProbability": 0.122413904830971, + "logBF": 34.6288023820744, + "pValueMantissa": 1.016, + "pValueExponent": -17, + "beta": -0.142225, + "standardError": 0.0165916, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11588262_T_C", + "posteriorProbability": 0.120006419495847, + "logBF": 34.608939654038, + "pValueMantissa": 9.658, + "pValueExponent": -18, + "beta": -0.141728, + "standardError": 0.0165224, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11587954_G_A", + "posteriorProbability": 0.118888519093094, + "logBF": 34.5995806565711, + "pValueMantissa": 9.745, + "pValueExponent": -18, + "beta": -0.141693, + "standardError": 0.0165203, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11587963_C_T", + "posteriorProbability": 0.11809942979467, + "logBF": 34.5929213119229, + "pValueMantissa": 9.802, + "pValueExponent": -18, + "beta": -0.141688, + "standardError": 0.016521, + "is95CredibleSet": true, + "is99CredibleSet": true + }, + { + "variantId": "2_11592421_G_GAATCAC", + "posteriorProbability": 0.112724255460893, + "logBF": 34.5463390362579, + "pValueMantissa": 1.04, + "pValueExponent": -17, + "beta": -0.141861, + "standardError": 0.0165544, + "is95CredibleSet": true, + "is99CredibleSet": true + } + ] + } + ] + } +}`), +}; +} + + diff --git a/packages/sections/src/variant/GWASCredibleSets/Description.tsx b/packages/sections/src/variant/GWASCredibleSets/Description.tsx new file mode 100644 index 000000000..aae73e1fc --- /dev/null +++ b/packages/sections/src/variant/GWASCredibleSets/Description.tsx @@ -0,0 +1,18 @@ +import { Link } from "ui"; + +type DescriptionProps = { + variantId: string; +}; + +function Description({ variantId }: DescriptionProps) { + return ( + <> + GWAS 99% credible sets containing {variantId}. Source{" "} + + Open Targets + + + ); +} + +export default Description; \ No newline at end of file diff --git a/packages/sections/src/variant/GWASCredibleSets/Summary.tsx b/packages/sections/src/variant/GWASCredibleSets/Summary.tsx new file mode 100644 index 000000000..be576bdcd --- /dev/null +++ b/packages/sections/src/variant/GWASCredibleSets/Summary.tsx @@ -0,0 +1,31 @@ +import { SummaryItem, usePlatformApi } from "ui"; + +import { definition } from "."; + +function Summary() { + + // !! USE PLACEHOLDER REQUEST FOR NOW !! + // const request = usePlatformApi(UNIPROT_VARIANTS_SUMMARY); + const request = { + loading: false, + error: undefined, + data: true, // data is not actually used by summary - only cares if there is data + }; + + return ( + {}} // !! renderSummary PROP NOT USED ANYMORE ANYWAY? + subText="" + // subText={dataTypesMapTyped.genetic_association} + /> + ); +} + +// !!!!!!!!!!!!! +// Summary.fragments = { +// ????????????? +// }; + +export default Summary; \ No newline at end of file diff --git a/packages/sections/src/variant/GWASCredibleSets/index.ts b/packages/sections/src/variant/GWASCredibleSets/index.ts new file mode 100644 index 000000000..8143d1912 --- /dev/null +++ b/packages/sections/src/variant/GWASCredibleSets/index.ts @@ -0,0 +1,14 @@ +// !!!!!!!!!! +// ADD POSSIBILITY FOR PRIVATE SECTIONS IN PARTNER PAGE +// !!!!!!!!!! +// import { isPrivateVariantSection } from "../../utils/partnerPreviewUtils"; + +// !! NEED TO TYPE WHATEVER PASSED INTO HASDATA - SEE SUMMARY +const id = "gwas_credible_sets"; +export const definition = { + id, + name: "GWAS Credible Sets", + shortName: "GW", + hasData: () => true, // !! CHANGE WHEN USE GQL !! + isPrivate: false, // isPrivateVariantSection(id), +}; From 5e76d1b7ecb4db7bae459751df82fef9ad1c2889 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Wed, 19 Jun 2024 13:50:57 +0100 Subject: [PATCH 06/17] [Platform] Add QTL credible sets widget to variant page (#396) --- .../src/pages/VariantPage/Profile.tsx | 8 +- .../src/variant/QTLCredibleSets/Body.tsx | 1122 +++++++++++++++++ .../variant/QTLCredibleSets/Description.tsx | 18 + .../src/variant/QTLCredibleSets/Summary.tsx | 31 + .../src/variant/QTLCredibleSets/index.ts | 14 + 5 files changed, 1192 insertions(+), 1 deletion(-) create mode 100644 packages/sections/src/variant/QTLCredibleSets/Body.tsx create mode 100644 packages/sections/src/variant/QTLCredibleSets/Description.tsx create mode 100644 packages/sections/src/variant/QTLCredibleSets/Summary.tsx create mode 100644 packages/sections/src/variant/QTLCredibleSets/index.ts diff --git a/apps/platform/src/pages/VariantPage/Profile.tsx b/apps/platform/src/pages/VariantPage/Profile.tsx index 471fb0c04..1af73b39a 100644 --- a/apps/platform/src/pages/VariantPage/Profile.tsx +++ b/apps/platform/src/pages/VariantPage/Profile.tsx @@ -9,6 +9,7 @@ import { import InSilicoPredictorsSummary from "sections/src/variant/InSilicoPredictors/Summary"; import EVASummary from "sections/src/variant/EVA/Summary"; import UniProtVariantsSummary from "sections/src/variant/UniProtVariants/Summary"; +import QTLCredibleSetsSummary from "sections/src/variant/QTLCredibleSets/Summary"; import GWASCredibleSetsSummary from "sections/src/variant/GWASCredibleSets/Summary"; import PharmacogenomicsSummary from "sections/src/variant/Pharmacogenomics/Summary"; @@ -17,6 +18,7 @@ import ProfileHeader from "./ProfileHeader"; const InSilicoPredictorsSection = lazy(() => import("sections/src/variant/InSilicoPredictors/Body")); const EVASection = lazy(() => import("sections/src/variant/EVA/Body")); const UniProtVariantsSection = lazy(() => import("sections/src/variant/UniProtVariants/Body")); +const QTLCredibleSetsSection = lazy(() => import("sections/src/variant/QTLCredibleSets/Body")); const GWASCredibleSetsSection = lazy(() => import("sections/src/variant/GWASCredibleSets/Body")); const PharmacogenomicsSection = lazy(() => import("sections/src/variant/Pharmacogenomics/Body")); @@ -24,6 +26,7 @@ const summaries = [ InSilicoPredictorsSummary, EVASummary, UniProtVariantsSummary, + QTLCredibleSetsSummary, GWASCredibleSetsSummary, PharmacogenomicsSummary, ]; @@ -54,6 +57,7 @@ function Profile({ varId }: ProfileProps) { + @@ -68,11 +72,13 @@ function Profile({ varId }: ProfileProps) { }> + }> + + }> - {/* NEED ANYTHING IN ???? see evidence page */} diff --git a/packages/sections/src/variant/QTLCredibleSets/Body.tsx b/packages/sections/src/variant/QTLCredibleSets/Body.tsx new file mode 100644 index 000000000..3516db94f --- /dev/null +++ b/packages/sections/src/variant/QTLCredibleSets/Body.tsx @@ -0,0 +1,1122 @@ +import { Link, SectionItem, DataTable, ScientificNotation } from "ui"; +import { Box, Chip } from "@mui/material"; +import { naLabel, defaultRowsPerPageOptions } from "../../constants"; +import { definition } from "."; +import Description from "./Description"; + +function getColumns(id: string, label: string) { + + return [ + { + id: "leadVariant", + label: "Lead Variant", + renderCell: ({ variantId }) => ( + variantId === id + ? + {variantId} + + + : {variantId} + ), + exportLabel: "Lead Variant", + }, + { + id: "study", + label: "Study", + renderCell: d => ( + + {d["study.projectId"]} + + ), + exportLabel: "Study", + }, + { + id: "type", + label: "Type", + renderCell: d => d["study.studyType"], + exportLabel: "Study", + }, + { + id: "tissue", + label: "Tissue", + renderCell: d => ( + + {d["tissue.label"] || ({d["tissue.id"]})} + + ), + exportLabel: "Tissue", + }, + { + id: "pValue", + label: "P-Value", + comparator: (a, b) => + a.pValueMantissa * 10 ** a.pValueExponent - b.pValueMantissa * 10 ** b.pValueExponent, + sortable: true, + renderCell: d => ( + + ), + exportLabel: "P-Value", + }, + { + id: "beta", + label: "Beta", + tooltip: "Beta with respect to the ALT allele", + renderCell: ({ beta }) => beta || beta === 0 ? beta.toPrecision(3) : naLabel, + exportLabel: "Beta", + }, + { + id: "fineMappingMethod", + label: "Finemapping Method", + renderCell: ({ finemappingMethod }) => finemappingMethod, + exportLabel: "Finemapping Method", + }, + { + id: "gene", + label: "Gene", + renderCell: d => ( + + {d["target.approvedSymbol"]} + + ), + exportLabel: "Gene", + }, + { + id: "credibleSetSize", + label: "Credible Set Size", + comparator: (a, b) => a.locus.length - b.locus.length, + sortable: true, + renderCell: ({ locus }) => locus.length, + exportLabel: "Credible Set Size", + } + ]; +} + +// !!!! LOAD LOCAL DATA FOR NOW +// const [metadata, setMetadata] = +// useState("waiting"); +const request = mockQuery(); + +type BodyProps = { + id: string, + label: string, + entity: string, +}; + +// !! FOR NOW, RENAME id AND SET IT MANUALLY BELOW +function Body({ id: doNotUseForNow, label, entity }: BodyProps) { + + // !! FOR NOW, SET id (IE THE PAGE VARIANT ID) TO FAKE TAG_VARIANT_ID + const id = request.data.TAG_VARIANT_ID; + + const columns = getColumns(id, label); + const rows = request.data.variant.gwasCredibleSets; + + return ( + } + renderBody={() => ( + + )} + /> + ); + +} + +export default Body; + +function mockQuery() { + return { + loading: false, + error: undefined, + data: JSON.parse(` +{ + "TAG_VARIANT_ID": "10_100315722_G_A", + "variant": { + "gwasCredibleSets": [ + { + "variantId": "2_8302417_G_A", + "study.id": "GTEx_brain_putamen_ENST00000668369", + "study.projectId": "GTEx", + "study.studyType": "eqtl", + "pValueMantissa": 2.359, + "pValueExponent": -8, + "beta": 0.694055, + "posteriorProbability": 0.0248072063095605, + "tissue.id": "UBERON_0001874", + "tissue.label": "putamen", + "tissue.organs": [ + "brain" + ], + "tissue.anatomicalSystems": [ + "nervous system" + ], + "target.approvedSymbol": "LINC00299", + "target.id": "ENSG00000236790", + "finemappingMethod": "SuSie", + "locus": [ + { + "beta": 0.642905, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.6040572828625, + "pValueExponent": -8, + "pValueMantissa": 1.124, + "posteriorProbability": 0.0711130529884503, + "standardError": 0.106521, + "variantId": "2_8300216_T_C" + }, + { + "beta": 0.642905, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.6040572828625, + "pValueExponent": -8, + "pValueMantissa": 1.124, + "posteriorProbability": 0.0711130529884503, + "standardError": 0.106521, + "variantId": "2_8300315_CACCA_C" + }, + { + "beta": 0.642905, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.6040572828625, + "pValueExponent": -8, + "pValueMantissa": 1.124, + "posteriorProbability": 0.0711130529884503, + "standardError": 0.106521, + "variantId": "2_8300442_G_A" + }, + { + "beta": 0.642905, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.6040572828625, + "pValueExponent": -8, + "pValueMantissa": 1.124, + "posteriorProbability": 0.0711130529884503, + "standardError": 0.106521, + "variantId": "2_8300228_C_A" + }, + { + "beta": 0.642905, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.6040572828625, + "pValueExponent": -8, + "pValueMantissa": 1.124, + "posteriorProbability": 0.0711130529884503, + "standardError": 0.106521, + "variantId": "2_8300184_A_G" + }, + { + "beta": 0.642905, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.6040572828625, + "pValueExponent": -8, + "pValueMantissa": 1.124, + "posteriorProbability": 0.0711130529884503, + "standardError": 0.106521, + "variantId": "2_8300257_G_A" + }, + { + "beta": 0.710524, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.599567286068, + "pValueExponent": -9, + "pValueMantissa": 7.823, + "posteriorProbability": 0.0709443341781754, + "standardError": 0.116336, + "variantId": "2_8302118_G_A" + }, + { + "beta": 0.710524, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.599567286068, + "pValueExponent": -9, + "pValueMantissa": 7.823, + "posteriorProbability": 0.0709443341781754, + "standardError": 0.116336, + "variantId": "2_8303673_G_A" + }, + { + "beta": 0.707031, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.3380989257068, + "pValueExponent": -8, + "pValueMantissa": 1.013, + "posteriorProbability": 0.05493800379884, + "standardError": 0.116746, + "variantId": "2_8301605_C_G" + }, + { + "beta": 0.627503, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.0559753546737, + "pValueExponent": -8, + "pValueMantissa": 1.981, + "posteriorProbability": 0.0416366528677439, + "standardError": 0.105964, + "variantId": "2_8301354_T_C" + }, + { + "beta": 0.627503, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.0559753546737, + "pValueExponent": -8, + "pValueMantissa": 1.981, + "posteriorProbability": 0.0416366528677439, + "standardError": 0.105964, + "variantId": "2_8299775_T_C" + }, + { + "beta": 0.627503, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.0559753546737, + "pValueExponent": -8, + "pValueMantissa": 1.981, + "posteriorProbability": 0.0416366528677439, + "standardError": 0.105964, + "variantId": "2_8301617_G_C" + }, + { + "beta": 0.627503, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.0559753546737, + "pValueExponent": -8, + "pValueMantissa": 1.981, + "posteriorProbability": 0.0416366528677439, + "standardError": 0.105964, + "variantId": "2_8301238_AG_A" + }, + { + "beta": 0.627503, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.0559753546737, + "pValueExponent": -8, + "pValueMantissa": 1.981, + "posteriorProbability": 0.0416366528677439, + "standardError": 0.105964, + "variantId": "2_8301922_G_A" + }, + { + "beta": 0.627503, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 17.0559753546737, + "pValueExponent": -8, + "pValueMantissa": 1.981, + "posteriorProbability": 0.0416366528677439, + 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+ "variantId": "2_8301605_C_G" + }, + { + "beta": 0.934523, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 44.7538794718291, + "pValueExponent": -11, + "pValueMantissa": 2.832, + "posteriorProbability": 0.0603001320652395, + "standardError": 0.126338, + "variantId": "2_8302118_G_A" + }, + { + "beta": 0.934523, + "is95CredibleSet": true, + "is99CredibleSet": true, + "logBF": 44.7538794718291, + "pValueExponent": -11, + "pValueMantissa": 2.832, + "posteriorProbability": 0.0603001320652395, + "standardError": 0.126338, + "variantId": "2_8303673_G_A" + } + ] + } + ] +} +}`), +}; +} \ No newline at end of file diff --git a/packages/sections/src/variant/QTLCredibleSets/Description.tsx b/packages/sections/src/variant/QTLCredibleSets/Description.tsx new file mode 100644 index 000000000..6dbdf8964 --- /dev/null +++ b/packages/sections/src/variant/QTLCredibleSets/Description.tsx @@ -0,0 +1,18 @@ +import { Link } from "ui"; + +type DescriptionProps = { + variantId: string; +}; + +function Description({ variantId }: DescriptionProps) { + return ( + <> + QTL 99% credible sets containing {variantId}. Source{" "} + + Open Targets + + + ); +} + +export default Description; \ No newline at end of file diff --git a/packages/sections/src/variant/QTLCredibleSets/Summary.tsx b/packages/sections/src/variant/QTLCredibleSets/Summary.tsx new file mode 100644 index 000000000..9879670cb --- /dev/null +++ b/packages/sections/src/variant/QTLCredibleSets/Summary.tsx @@ -0,0 +1,31 @@ +import { SummaryItem, usePlatformApi } from "ui"; + +import { definition } from "."; + +function Summary() { + + // !! USE PLACEHOLDER REQUEST FOR NOW !! + // const request = usePlatformApi(UNIPROT_VARIANTS_SUMMARY); + const request = { + loading: false, + error: undefined, + data: true, // data is not actually used by summary - only cares if there is data + }; + + return ( + {}} // !! renderSummary PROP NOT USED ANYMORE ANYWAY? + subText="" + // subText={dataTypesMapTyped.genetic_association} + /> + ); +} + +// !!!!!!!!!!!!! +// Summary.fragments = { +// ????????????? +// }; + +export default Summary; \ No newline at end of file diff --git a/packages/sections/src/variant/QTLCredibleSets/index.ts b/packages/sections/src/variant/QTLCredibleSets/index.ts new file mode 100644 index 000000000..67710463a --- /dev/null +++ b/packages/sections/src/variant/QTLCredibleSets/index.ts @@ -0,0 +1,14 @@ +// !!!!!!!!!! +// ADD POSSIBILITY FOR PRIVATE SECTIONS IN PARTNER PAGE +// !!!!!!!!!! +// import { isPrivateVariantSection } from "../../utils/partnerPreviewUtils"; + +// !! NEED TO TYPE WHATEVER PASSED INTO HASDATA - SEE SUMMARY +const id = "qtl_credible_sets"; +export const definition = { + id, + name: "QTL Credible Sets", + shortName: "QT", + hasData: () => true, // !! CHANGE WHEN USE GQL !! + isPrivate: false, // isPrivateVariantSection(id), +}; \ No newline at end of file From 31c4aeb793ffc8b5b8afc187aaf3c818f047c450 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Wed, 3 Jul 2024 14:05:21 +0100 Subject: [PATCH 07/17] [Platform] Add Uniprot id to Uniprot description link (#401) --- .../sections/src/variant/UniProtVariants/Description.tsx | 5 +++-- 1 file changed, 3 insertions(+), 2 deletions(-) diff --git a/packages/sections/src/variant/UniProtVariants/Description.tsx b/packages/sections/src/variant/UniProtVariants/Description.tsx index 1b2900326..b86b06d2e 100644 --- a/packages/sections/src/variant/UniProtVariants/Description.tsx +++ b/packages/sections/src/variant/UniProtVariants/Description.tsx @@ -7,11 +7,12 @@ type DescriptionProps = { }; function Description({ variantId, data }: DescriptionProps) { + const { targetFromSourceId } = data.variant.uniProtVariants[0]; return ( <> Literature-based curation associating {variantId}{" "} to a disease/phenotype. Source:{" "} - - UniProt + + UniProt ({targetFromSourceId}) ); From 0a27b9375c6a5f6b449d059b2a2797f077188641 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Wed, 3 Jul 2024 14:06:11 +0100 Subject: [PATCH 08/17] [Platform] Add allele frequency plot to variant page metadata section (#403) * frequency vis examples * polish plots * allele frequency bars * use flex for allele frequency plot * do not import grid --- .../public/data/variant-data-fake.json | 792 ++++++++++++++++++ .../src/pages/VariantPage/ProfileHeader.tsx | 97 ++- .../src/pages/VariantPage/VariantPage.tsx | 2 +- 3 files changed, 857 insertions(+), 34 deletions(-) create mode 100644 apps/platform/public/data/variant-data-fake.json diff --git a/apps/platform/public/data/variant-data-fake.json b/apps/platform/public/data/variant-data-fake.json new file mode 100644 index 000000000..f95ca8e51 --- /dev/null +++ b/apps/platform/public/data/variant-data-fake.json @@ -0,0 +1,792 @@ +[ + { + "variantId": "20_31257670_C_T", + "chromosome": "20", + "position": 31257670, + "chromosomeB37": "20", + "positionB37": 29845473, + "referenceAllele": "C", + "alternateAllele": "T", + "rsIds": [ + "rs191451885" + ], + "alleleType": "snv", + "alleleFrequencies": [ + { + "populationName": "afr_adj", + "alleleFrequency": 0.129 + }, + { + "populationName": "ami_adj", + "alleleFrequency": 0.193 + }, + { + "populationName": "amr_adj", + "alleleFrequency": 0.249 + }, + { + "populationName": "asj_adj", + "alleleFrequency": 0.53 + }, + { + "populationName": "eas_adj", + "alleleFrequency": 0.620 + }, + { + "populationName": "fin_adj", + "alleleFrequency": 0.225 + }, + { + "populationName": "mid_adj", + "alleleFrequency": 0.429 + }, + { + "populationName": "nfe_adj", + "alleleFrequency": 0.287 + }, + { + "populationName": "remaining_adj", + "alleleFrequency": 0.011 + }, + { + "populationName": "sas_adj", + "alleleFrequency": 0.302 + } + ], + "vep": { + "mostSevereConsequence": "missense_variant", + "transcriptConsequences": [ + { + "aminoAcids": "P/S", + "consequenceTerms": [ + "missense_variant" + ], + "geneId": "ENSG00000215547" + } + ] + }, + "inSilicoPredictors": { + "cadd": { + "phred": 3.639, + "raw": 0.24446 + }, + "revelMax": 0.02, + "spliceaiDsMax": 0, + "pangolinLargestDs": 0, + "phylop": 1.393, + "siftMax": 0.21, + "polyphenMax": 0.026 + } + }, + { + "variantId": "20_31257685_C_A", + "chromosome": "20", + "position": 31257685, + "chromosomeB37": "20", + "positionB37": 29845488, + "referenceAllele": "C", + "alternateAllele": "A", + "rsIds": [ + "rs946177627" + ], + "alleleType": "snv", + "alleleFrequencies": [ + { + "populationName": "afr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "ami_adj", + "alleleFrequency": 0 + }, + { + "populationName": "amr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "asj_adj", + "alleleFrequency": 0 + }, + { + "populationName": "eas_adj", + "alleleFrequency": 0 + }, + { + "populationName": "fin_adj", + "alleleFrequency": 0 + }, + { + "populationName": "mid_adj", + "alleleFrequency": 0 + }, + { + "populationName": "nfe_adj", + "alleleFrequency": 0.000014698965192850424 + }, + { + "populationName": "remaining_adj", + "alleleFrequency": 0 + }, + { + "populationName": "sas_adj", + "alleleFrequency": 0 + } + ], + "vep": { + "mostSevereConsequence": "missense_variant", + "transcriptConsequences": [ + { + "aminoAcids": "P/T", + "consequenceTerms": [ + "missense_variant" + ], + "geneId": "ENSG00000215547" + } + ] + }, + "inSilicoPredictors": { + "cadd": { + "phred": 0.18, + "raw": -0.413358 + }, + "revelMax": 0.033, + "spliceaiDsMax": 0, + "pangolinLargestDs": 0, + "phylop": -0.815, + "siftMax": 1, + "polyphenMax": 0.026 + } + }, + { + "variantId": "20_31257685_C_G", + "chromosome": "20", + "position": 31257685, + "chromosomeB37": "20", + "positionB37": 29845488, + "referenceAllele": "C", + "alternateAllele": "G", + "rsIds": [ + "rs946177627" + ], + "alleleType": "snv", + "alleleFrequencies": [ + { + "populationName": "afr_adj", + "alleleFrequency": 0.00004825789016504198 + }, + { + "populationName": "ami_adj", + "alleleFrequency": 0 + }, + { + "populationName": "amr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "asj_adj", + "alleleFrequency": 0 + }, + { + "populationName": "eas_adj", + "alleleFrequency": 0 + }, + { + "populationName": "fin_adj", + "alleleFrequency": 0 + }, + { + "populationName": "mid_adj", + "alleleFrequency": 0 + }, + { + "populationName": "nfe_adj", + "alleleFrequency": 0 + }, + { + "populationName": "remaining_adj", + "alleleFrequency": 0 + }, + { + "populationName": "sas_adj", + "alleleFrequency": 0 + } + ], + "vep": { + "mostSevereConsequence": "missense_variant", + "transcriptConsequences": [ + { + "aminoAcids": "P/A", + "consequenceTerms": [ + "missense_variant" + ], + "geneId": "ENSG00000215547" + } + ] + }, + "inSilicoPredictors": { + "cadd": { + "phred": 0.715, + "raw": -0.130967 + }, + "revelMax": 0.032, + "spliceaiDsMax": 0, + "pangolinLargestDs": 0, + "phylop": -0.815, + "siftMax": 0.46, + "polyphenMax": 0.098 + } + }, + { + "variantId": "20_31257688_C_G", + "chromosome": "20", + "position": 31257688, + "chromosomeB37": "20", + "positionB37": 29845491, + "referenceAllele": "C", + "alternateAllele": "G", + "rsIds": [ + "rs1253802045" + ], + "alleleType": "snv", + "alleleFrequencies": [ + { + "populationName": "afr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "ami_adj", + "alleleFrequency": 0 + }, + { + "populationName": "amr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "asj_adj", + "alleleFrequency": 0 + }, + { + "populationName": "eas_adj", + "alleleFrequency": 0 + }, + { + "populationName": "fin_adj", + "alleleFrequency": 0 + }, + { + "populationName": "mid_adj", + "alleleFrequency": 0 + }, + { + "populationName": "nfe_adj", + "alleleFrequency": 0.00001470112610625974 + }, + { + "populationName": "remaining_adj", + "alleleFrequency": 0 + }, + { + "populationName": "sas_adj", + "alleleFrequency": 0 + } + ], + "vep": { + "mostSevereConsequence": "missense_variant", + "transcriptConsequences": [ + { + "aminoAcids": "L/V", + "consequenceTerms": [ + "missense_variant" + ], + "geneId": "ENSG00000215547" + } + ] + }, + "inSilicoPredictors": { + "cadd": { + "phred": 0.623, + "raw": -0.159595 + }, + "revelMax": 0.053, + "spliceaiDsMax": 0, + "pangolinLargestDs": 0.01, + "phylop": -0.049, + "siftMax": 0.05, + "polyphenMax": 0.224 + } + }, + { + "variantId": "20_31257701_T_G", + "chromosome": "20", + "position": 31257701, + "chromosomeB37": "20", + "positionB37": 29845504, + "referenceAllele": "T", + "alternateAllele": "G", + "rsIds": [ + "rs1197497818" + ], + "alleleType": "snv", + "alleleFrequencies": [ + { + "populationName": "afr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "ami_adj", + "alleleFrequency": 0 + }, + { + "populationName": "amr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "asj_adj", + "alleleFrequency": 0 + }, + { + "populationName": "eas_adj", + "alleleFrequency": 0 + }, + { + "populationName": "fin_adj", + "alleleFrequency": 0.00009416195856873823 + }, + { + "populationName": "mid_adj", + "alleleFrequency": 0 + }, + { + "populationName": "nfe_adj", + "alleleFrequency": 0 + }, + { + "populationName": "remaining_adj", + "alleleFrequency": 0 + }, + { + "populationName": "sas_adj", + "alleleFrequency": 0 + } + ], + "vep": { + "mostSevereConsequence": "missense_variant", + "transcriptConsequences": [ + { + "aminoAcids": "I/S", + "consequenceTerms": [ + "missense_variant" + ], + "geneId": "ENSG00000215547" + } + ] + }, + "inSilicoPredictors": { + "cadd": { + "phred": 10.76, + "raw": 0.929881 + }, + "revelMax": 0.011, + "spliceaiDsMax": 0, + "pangolinLargestDs": 0, + "phylop": 0.103, + "siftMax": 0.22, + "polyphenMax": 0.076 + } + }, + { + "variantId": "20_31257719_C_A", + "chromosome": "20", + "position": 31257719, + "chromosomeB37": "20", + "positionB37": 29845522, + "referenceAllele": "C", + "alternateAllele": "A", + "rsIds": [ + "rs769167828" + ], + "alleleType": "snv", + "alleleFrequencies": [ + { + "populationName": "afr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "ami_adj", + "alleleFrequency": 0 + }, + { + "populationName": "amr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "asj_adj", + "alleleFrequency": 0 + }, + { + "populationName": "eas_adj", + "alleleFrequency": 0 + }, + { + "populationName": "fin_adj", + "alleleFrequency": 0 + }, + { + "populationName": "mid_adj", + "alleleFrequency": 0 + }, + { + "populationName": "nfe_adj", + "alleleFrequency": 0.000014700261664657632 + }, + { + "populationName": "remaining_adj", + "alleleFrequency": 0 + }, + { + "populationName": "sas_adj", + "alleleFrequency": 0 + } + ], + "vep": { + "mostSevereConsequence": "missense_variant", + "transcriptConsequences": [ + { + "aminoAcids": "A/D", + "consequenceTerms": [ + "missense_variant" + ], + "geneId": "ENSG00000215547" + } + ] + }, + "inSilicoPredictors": { + "cadd": { + "phred": 19.9, + "raw": 2.084135 + }, + "revelMax": 0.165, + "spliceaiDsMax": 0, + "pangolinLargestDs": 0, + "phylop": 0.949, + "siftMax": 0.02, + "polyphenMax": 0.948 + } + }, + { + "variantId": "20_31257722_T_C", + "chromosome": "20", + "position": 31257722, + "chromosomeB37": "20", + "positionB37": 29845525, + "referenceAllele": "T", + "alternateAllele": "C", + "rsIds": [ + "rs374301214" + ], + "alleleType": "snv", + "alleleFrequencies": [ + { + "populationName": "afr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "ami_adj", + "alleleFrequency": 0 + }, + { + "populationName": "amr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "asj_adj", + "alleleFrequency": 0 + }, + { + "populationName": "eas_adj", + "alleleFrequency": 0 + }, + { + "populationName": "fin_adj", + "alleleFrequency": 0.00018839487565938207 + }, + { + "populationName": "mid_adj", + "alleleFrequency": 0 + }, + { + "populationName": "nfe_adj", + "alleleFrequency": 0.00001470112610625974 + }, + { + "populationName": "remaining_adj", + "alleleFrequency": 0 + }, + { + "populationName": "sas_adj", + "alleleFrequency": 0 + } + ], + "vep": { + "mostSevereConsequence": "missense_variant", + "transcriptConsequences": [ + { + "aminoAcids": "L/S", + "consequenceTerms": [ + "missense_variant" + ], + "geneId": "ENSG00000215547" + } + ] + }, + "inSilicoPredictors": { + "cadd": { + "phred": 23.6, + "raw": 3.066376 + }, + "revelMax": 0.144, + "spliceaiDsMax": 0, + "pangolinLargestDs": 0, + "phylop": 3.355, + "siftMax": 0, + "polyphenMax": 0.646 + } + }, + { + "variantId": "20_31257727_G_T", + "chromosome": "20", + "position": 31257727, + "chromosomeB37": "20", + "positionB37": 29845530, + "referenceAllele": "G", + "alternateAllele": "T", + "rsIds": [ + "rs767578245" + ], + "alleleType": "snv", + "alleleFrequencies": [ + { + "populationName": "afr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "ami_adj", + "alleleFrequency": 0 + }, + { + "populationName": "amr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "asj_adj", + "alleleFrequency": 0 + }, + { + "populationName": "eas_adj", + "alleleFrequency": 0 + }, + { + "populationName": "fin_adj", + "alleleFrequency": 0 + }, + { + "populationName": "mid_adj", + "alleleFrequency": 0 + }, + { + "populationName": "nfe_adj", + "alleleFrequency": 0.000014703287655119684 + }, + { + "populationName": "remaining_adj", + "alleleFrequency": 0 + }, + { + "populationName": "sas_adj", + "alleleFrequency": 0.00020738282870178348 + } + ], + "vep": { + "mostSevereConsequence": "missense_variant", + "transcriptConsequences": [ + { + "aminoAcids": "V/F", + "consequenceTerms": [ + "missense_variant" + ], + "geneId": "ENSG00000215547" + } + ] + }, + "inSilicoPredictors": { + "cadd": { + "phred": 23.1, + "raw": 2.849272 + }, + "revelMax": 0.134, + "spliceaiDsMax": 0.01, + "pangolinLargestDs": 0, + "phylop": 1.58, + "siftMax": 0.01, + "polyphenMax": 0.98 + } + }, + { + "variantId": "20_31257731_T_C", + "chromosome": "20", + "position": 31257731, + "chromosomeB37": "20", + "positionB37": 29845534, + "referenceAllele": "T", + "alternateAllele": "C", + "rsIds": [ + "rs760827610" + ], + "alleleType": "snv", + "alleleFrequencies": [ + { + "populationName": "afr_adj", + "alleleFrequency": 0.000024127780726728754 + }, + { + "populationName": "ami_adj", + "alleleFrequency": 0 + }, + { + "populationName": "amr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "asj_adj", + "alleleFrequency": 0 + }, + { + "populationName": "eas_adj", + "alleleFrequency": 0 + }, + { + "populationName": "fin_adj", + "alleleFrequency": 0 + }, + { + "populationName": "mid_adj", + "alleleFrequency": 0 + }, + { + "populationName": "nfe_adj", + "alleleFrequency": 0 + }, + { + "populationName": "remaining_adj", + "alleleFrequency": 0 + }, + { + "populationName": "sas_adj", + "alleleFrequency": 0 + } + ], + "vep": { + "mostSevereConsequence": "missense_variant", + "transcriptConsequences": [ + { + "aminoAcids": "L/P", + "consequenceTerms": [ + "missense_variant" + ], + "geneId": "ENSG00000215547" + } + ] + }, + "inSilicoPredictors": { + "cadd": { + "phred": 23.2, + "raw": 2.887348 + }, + "revelMax": 0.182, + "spliceaiDsMax": 0, + "pangolinLargestDs": 0, + "phylop": 1.325, + "siftMax": 0.01, + "polyphenMax": 0.973 + } + }, + { + "variantId": "20_31257736_G_A", + "chromosome": "20", + "position": 31257736, + "chromosomeB37": "20", + "positionB37": 29845539, + "referenceAllele": "G", + "alternateAllele": "A", + "rsIds": [ + "rs754890194" + ], + "alleleType": "snv", + "alleleFrequencies": [ + { + "populationName": "afr_adj", + "alleleFrequency": 0.00007241479192816453 + }, + { + "populationName": "ami_adj", + "alleleFrequency": 0 + }, + { + "populationName": "amr_adj", + "alleleFrequency": 0 + }, + { + "populationName": "asj_adj", + "alleleFrequency": 0 + }, + { + "populationName": "eas_adj", + "alleleFrequency": 0 + }, + { + "populationName": "fin_adj", + "alleleFrequency": 0 + }, + { + "populationName": "mid_adj", + "alleleFrequency": 0 + }, + { + "populationName": "nfe_adj", + "alleleFrequency": 0 + }, + { + "populationName": "remaining_adj", + "alleleFrequency": 0 + }, + { + "populationName": "sas_adj", + "alleleFrequency": 0 + } + ], + "vep": { + "mostSevereConsequence": "missense_variant", + "transcriptConsequences": [ + { + "aminoAcids": "V/I", + "consequenceTerms": [ + "missense_variant" + ], + "geneId": "ENSG00000215547" + } + ] + }, + "inSilicoPredictors": { + "cadd": { + "phred": 11.31, + "raw": 0.974809 + }, + "revelMax": 0.05, + "spliceaiDsMax": 0, + "pangolinLargestDs": 0, + "phylop": 0.631, + "siftMax": 0.3, + "polyphenMax": 0.328 + } + } +] \ No newline at end of file diff --git a/apps/platform/src/pages/VariantPage/ProfileHeader.tsx b/apps/platform/src/pages/VariantPage/ProfileHeader.tsx index 7a1036cfa..7615758c8 100644 --- a/apps/platform/src/pages/VariantPage/ProfileHeader.tsx +++ b/apps/platform/src/pages/VariantPage/ProfileHeader.tsx @@ -1,7 +1,6 @@ import { useState, useEffect } from "react"; import { Field, ProfileHeader as BaseProfileHeader } from "ui"; import { Box, Typography } from "@mui/material"; -import { InSilicoPredictorsType, MetadataType } from "./types"; type ProfileHeaderProps = { varId: string; @@ -13,7 +12,7 @@ function ProfileHeader({ varId }: ProfileHeaderProps) { const [metadata, setMetadata] = useState("waiting"); useEffect(() => { - fetch("../data/variant-data-2.json") + fetch("../data/variant-data-fake.json") .then(response => response.json()) .then((allData: MetadataType[]) => setMetadata(allData.find(v => v.variantId === varId))); @@ -50,25 +49,8 @@ function ProfileHeader({ varId }: ProfileHeaderProps) { - Population Allele Frequencies - - {metadata.alleleFrequencies - .map(({populationName, alleleFrequency }) => ( - - - - - )) - } -
- - {populationLabels[populationName as keyof typeof populationLabels]} - - - - {alleleFrequency.toFixed(3)} - -
+ Population Allele Frequencies + @@ -77,16 +59,65 @@ function ProfileHeader({ varId }: ProfileHeaderProps) { export default ProfileHeader; -// !! NEEDS CHECKED SINCE DIFFERENT KEYS TO THOSE USED ON CURRENT VARIANT PAGE +// THESE NEED CHECKED!! const populationLabels = { - afr_adj: 'African/African-American', - amr_adj: 'Latino/Admixed American', - asj_adj: 'Ashkenazi Jewish', - eas_adj: 'East Asian', - fin_adj: 'Finnish', - nfe_adj: 'Non-Finnish European', - ami_adj: 'Non-Finnish European Estonian', - mid_adj: 'Non-Finnish European North-Western European', - sas_adj: 'Non-Finnish European Southern European', - remaining_adj: 'Other (population not assigned)', -}; \ No newline at end of file + // from AB (orig from YT) + afr_adj: "African-American", + amr_adj: "American Admixed/Latino", + asj_adj: "Ashkenazi Jewish", + eas_adj: "East Asian", + fin_adj: "Finnish", + nfe_adj: "Non-Finnish European", + // nwe_adj: "Northwestern European", + // seu_adj: "Southeastern European", + // add in missing from above - + ami_adj: "Amish", // from https://www.pharmgkb.org/variant/PA166175994 + mid_adj: "Middle Eastern", // guessed from: https://gnomad.broadinstitute.org/variant/1-154453788-C-T?dataset=gnomad_r4 + sas_adj: "South Asian", // from https://www.pharmgkb.org/variant/PA166175994 + remaining_adj: 'Other', +}; + +function AlleleFrequencyPlot({ data }) { + + // sort rows alphabetically on population label - but put "other" last + const rows = data.map(({ populationName, alleleFrequency }) => ({ + label: populationLabels[populationName], + alleleFrequency, + })).sort((a, b) => a.label < b.label ? -1 : 1); + rows.push(rows.splice(rows.findIndex(r => r.label === 'Other'), 1)[0]); + + return( + + {rows.map(row => ( + + ))} + + ); +} + +function BarGroup({ dataRow: { label, alleleFrequency } }) { + return ( + + + {label} + + theme.palette.grey[300], + height: "9px" + }}> + + + + {alleleFrequency.toFixed(3)} + + + ); +} \ No newline at end of file diff --git a/apps/platform/src/pages/VariantPage/VariantPage.tsx b/apps/platform/src/pages/VariantPage/VariantPage.tsx index 8cf8f648a..ecd0609a0 100644 --- a/apps/platform/src/pages/VariantPage/VariantPage.tsx +++ b/apps/platform/src/pages/VariantPage/VariantPage.tsx @@ -23,7 +23,7 @@ function VariantPage() { // temp: data will come from gql, fetch local json file for now const [metadata, setMetadata] = useState("waiting"); useEffect(() => { - fetch("../data/variant-data-2.json") + fetch("../data/variant-data-fake.json") .then(response => response.json()) .then((allData: MetadataType[]) => setMetadata(allData.find(v => v.variantId === varId))); }, []); From 31755828df16b1f78609b4b06e17fc96305e5aa6 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Wed, 3 Jul 2024 14:06:57 +0100 Subject: [PATCH 09/17] [Platform] Clean up variant page sections and summaries (#404) --- apps/platform/src/pages/VariantPage/Profile.tsx | 2 ++ packages/sections/src/variant/EVA/Summary.tsx | 7 ------- .../sections/src/variant/InSilicoPredictors/Summary.tsx | 7 ------- packages/sections/src/variant/UniProtVariants/Summary.tsx | 7 ------- 4 files changed, 2 insertions(+), 21 deletions(-) diff --git a/apps/platform/src/pages/VariantPage/Profile.tsx b/apps/platform/src/pages/VariantPage/Profile.tsx index 1af73b39a..407445f56 100644 --- a/apps/platform/src/pages/VariantPage/Profile.tsx +++ b/apps/platform/src/pages/VariantPage/Profile.tsx @@ -77,6 +77,8 @@ function Profile({ varId }: ProfileProps) { }> + + }> diff --git a/packages/sections/src/variant/EVA/Summary.tsx b/packages/sections/src/variant/EVA/Summary.tsx index 437471d25..bd78d8546 100644 --- a/packages/sections/src/variant/EVA/Summary.tsx +++ b/packages/sections/src/variant/EVA/Summary.tsx @@ -6,12 +6,6 @@ import { dataTypesMap } from "../../dataTypes"; function Summary() { - // !! THIS IS UGLY BUT AVOIDS ADDING TYPES IN dataType FILE FOR NOW - type dataTypesMapType = { - [index: string]: number; - }; - const dataTypesMapTyped = dataTypesMap as dataTypesMapType; - // !! USE PLACEHOLDER REQUEST FOR NOW !! // const request = usePlatformApi(EVA_SUMMARY); const request = { @@ -29,7 +23,6 @@ function Summary() { // const { count } = evaSummary; // return `${count} ${count === 1 ? "entry" : "entries"}`; // }} - subText={dataTypesMapTyped.genetic_association} /> ); } diff --git a/packages/sections/src/variant/InSilicoPredictors/Summary.tsx b/packages/sections/src/variant/InSilicoPredictors/Summary.tsx index fd8d58567..266cbf62d 100644 --- a/packages/sections/src/variant/InSilicoPredictors/Summary.tsx +++ b/packages/sections/src/variant/InSilicoPredictors/Summary.tsx @@ -6,12 +6,6 @@ import { dataTypesMap } from "../../dataTypes"; function Summary() { - // !! THIS IS UGLY BUT AVOIDS ADDING TYPES IN dataType FILE FOR NOW - type dataTypesMapType = { - [index: string]: number; - }; - const dataTypesMapTyped = dataTypesMap as dataTypesMapType; - // !! USE PLACEHOLDER REQUEST FOR NOW !! // const request = usePlatformApi(UNIPROT_VARIANTS_SUMMARY); const request = { @@ -29,7 +23,6 @@ function Summary() { // const { count } = uniprotVariantsSummary; // return `${count} ${count === 1 ? "entry" : "entries"}`; // }} - subText={dataTypesMapTyped.genetic_association} // !! LEAVE AS GENETIC ASSOCITION FOR NOW /> ); } diff --git a/packages/sections/src/variant/UniProtVariants/Summary.tsx b/packages/sections/src/variant/UniProtVariants/Summary.tsx index ba8a8ed22..266cbf62d 100644 --- a/packages/sections/src/variant/UniProtVariants/Summary.tsx +++ b/packages/sections/src/variant/UniProtVariants/Summary.tsx @@ -6,12 +6,6 @@ import { dataTypesMap } from "../../dataTypes"; function Summary() { - // !! THIS IS UGLY BUT AVOIDS ADDING TYPES IN dataType FILE FOR NOW - type dataTypesMapType = { - [index: string]: number; - }; - const dataTypesMapTyped = dataTypesMap as dataTypesMapType; - // !! USE PLACEHOLDER REQUEST FOR NOW !! // const request = usePlatformApi(UNIPROT_VARIANTS_SUMMARY); const request = { @@ -29,7 +23,6 @@ function Summary() { // const { count } = uniprotVariantsSummary; // return `${count} ${count === 1 ? "entry" : "entries"}`; // }} - subText={dataTypesMapTyped.genetic_association} /> ); } From 65382c6b9e18f998796f4d4eeca05b6d5a216b6b Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Wed, 3 Jul 2024 14:07:30 +0100 Subject: [PATCH 10/17] [Platform] Update variant page QTL credible sets widget (#406) --- .../src/variant/QTLCredibleSets/Body.tsx | 26 +++++++++---------- .../variant/QTLCredibleSets/Description.tsx | 6 ++--- .../src/variant/QTLCredibleSets/index.ts | 2 +- 3 files changed, 17 insertions(+), 17 deletions(-) diff --git a/packages/sections/src/variant/QTLCredibleSets/Body.tsx b/packages/sections/src/variant/QTLCredibleSets/Body.tsx index 3516db94f..ad6209d7f 100644 --- a/packages/sections/src/variant/QTLCredibleSets/Body.tsx +++ b/packages/sections/src/variant/QTLCredibleSets/Body.tsx @@ -37,14 +37,24 @@ function getColumns(id: string, label: string) { exportLabel: "Study", }, { - id: "tissue", - label: "Tissue", + id: "gene", + label: "Gene", + renderCell: d => ( + + {d["target.approvedSymbol"]} + + ), + exportLabel: "Gene", + }, + { + id: "tissueCell", + label: "Tissue/Cell", renderCell: d => ( {d["tissue.label"] || ({d["tissue.id"]})} ), - exportLabel: "Tissue", + exportLabel: "Tissue/Cell", }, { id: "pValue", @@ -70,16 +80,6 @@ function getColumns(id: string, label: string) { renderCell: ({ finemappingMethod }) => finemappingMethod, exportLabel: "Finemapping Method", }, - { - id: "gene", - label: "Gene", - renderCell: d => ( - - {d["target.approvedSymbol"]} - - ), - exportLabel: "Gene", - }, { id: "credibleSetSize", label: "Credible Set Size", diff --git a/packages/sections/src/variant/QTLCredibleSets/Description.tsx b/packages/sections/src/variant/QTLCredibleSets/Description.tsx index 6dbdf8964..90d8ed8bd 100644 --- a/packages/sections/src/variant/QTLCredibleSets/Description.tsx +++ b/packages/sections/src/variant/QTLCredibleSets/Description.tsx @@ -7,9 +7,9 @@ type DescriptionProps = { function Description({ variantId }: DescriptionProps) { return ( <> - QTL 99% credible sets containing {variantId}. Source{" "} - - Open Targets + molQTL 99% credible sets containing {variantId}. Source{" "} + + eQTL Catalog ); diff --git a/packages/sections/src/variant/QTLCredibleSets/index.ts b/packages/sections/src/variant/QTLCredibleSets/index.ts index 67710463a..8506717da 100644 --- a/packages/sections/src/variant/QTLCredibleSets/index.ts +++ b/packages/sections/src/variant/QTLCredibleSets/index.ts @@ -7,7 +7,7 @@ const id = "qtl_credible_sets"; export const definition = { id, - name: "QTL Credible Sets", + name: "molQTL Credible Sets", shortName: "QT", hasData: () => true, // !! CHANGE WHEN USE GQL !! isPrivate: false, // isPrivateVariantSection(id), From f8ff9b745396f32d20edc6935e32228a01beebf7 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Wed, 10 Jul 2024 14:11:52 +0100 Subject: [PATCH 11/17] [Platform] Use API for variant page header (#412) --- apps/platform/.env | 2 +- .../platform/src/pages/VariantPage/Header.tsx | 94 +++++++++++++------ .../src/pages/VariantPage/VariantPage.gql | 13 +++ .../src/pages/VariantPage/VariantPage.tsx | 32 +++---- apps/platform/src/pages/VariantPage/types.ts | 17 ++++ .../src/components/ExternalLink/XRefLinks.tsx | 10 +- 6 files changed, 117 insertions(+), 51 deletions(-) create mode 100644 apps/platform/src/pages/VariantPage/VariantPage.gql diff --git a/apps/platform/.env b/apps/platform/.env index 4ceb89976..10e7d0df2 100644 --- a/apps/platform/.env +++ b/apps/platform/.env @@ -1,3 +1,3 @@ -VITE_API_URL=https://api.platform.dev.opentargets.xyz/api/v4/graphql +VITE_API_URL=https://api.genetics.dev.opentargets.xyz/api/v4/graphql VITE_AI_API_URL=https://dev-ai-api-w37vlfsidq-ew.a.run.app VITE_PROFILE=default \ No newline at end of file diff --git a/apps/platform/src/pages/VariantPage/Header.tsx b/apps/platform/src/pages/VariantPage/Header.tsx index 58b7a6f3b..f70665d39 100644 --- a/apps/platform/src/pages/VariantPage/Header.tsx +++ b/apps/platform/src/pages/VariantPage/Header.tsx @@ -1,27 +1,62 @@ import { faMapPin } from "@fortawesome/free-solid-svg-icons"; -import { Header as HeaderBase, ExternalLink } from "ui"; -import { MetadataType } from "./types"; +import { Header as HeaderBase, XRefLinks } from "ui"; +import { VariantPageDataType } from "./types"; + +const xrefsToDisplay = { + ensemblVariation: { + label: "Ensembl", + urlStem: "https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=", + }, + gnomad: { + label: "gnomAD", + urlBuilder: id => `https://gnomad.broadinstitute.org/variant/${id}?dataset=gnomad_r4`, + }, + protvar: { + label: "ProtVar", + urlBuilder: (id, { chromosome, position, referenceAllele, alternateAllele }) => ( + `https://www.ebi.ac.uk/ProtVar/query?chromosome=${chromosome + }&genomic_position=${position + }&reference_allele=${referenceAllele + }&alternative_allele=${alternateAllele}` + ), + }, + clinVar: { + label: "ClinVar", + urlStem: "https://www.ncbi.nlm.nih.gov/clinvar/variation/", + }, + omim: { + label: "OMIM", + urlStem: "https://www.omim.org/entry/", + }, +}; + +function processXRefs(dbXRefs) { + const xrefs = {}; + for (const { id, source } of dbXRefs) { + const { label, urlBuilder, urlStem } = xrefsToDisplay[source]; + if (xrefs[source]) { + xrefs[source].ids.add(id); + } else { + xrefs[source] = { + label, + urlStem, + urlBuilder, + ids: new Set([id]), + }; + } + } + return xrefs; +} type HeaderProps = { loading: boolean; - metadata: MetadataType; + variantId: string; + variantPageData: VariantPageDataType; }; -function Header({ loading, metadata }: HeaderProps) { - const { - variantId, - rsIds, - chromosome, - position, - referenceAllele, - alternateAllele, - } = metadata; - const rsId = rsIds[0]; - const gnomadId = `${ - chromosome}-${ - position}-${ - referenceAllele}-${ - alternateAllele}`; +function Header({ loading, variantId, variantPageData }: HeaderProps) { + + const xrefs = processXRefs(variantPageData?.dbXrefs || []); return ( - - + {Object.keys(xrefs).map(xref => { + const { label, urlBuilder, urlStem, ids } = xrefs[xref]; + return ( + urlBuilder(id, variantPageData)) : null} + ids={[...ids]} + limit="3" + /> + ); + })} } /> diff --git a/apps/platform/src/pages/VariantPage/VariantPage.gql b/apps/platform/src/pages/VariantPage/VariantPage.gql new file mode 100644 index 000000000..58d01a76c --- /dev/null +++ b/apps/platform/src/pages/VariantPage/VariantPage.gql @@ -0,0 +1,13 @@ +query VariantPageQuery($variantId: String!) { + variant(variantId: $variantId) { + variantId + dbXrefs { + id + source + } + chromosome + position + referenceAllele + alternateAllele + } +} diff --git a/apps/platform/src/pages/VariantPage/VariantPage.tsx b/apps/platform/src/pages/VariantPage/VariantPage.tsx index ecd0609a0..0b4acd231 100644 --- a/apps/platform/src/pages/VariantPage/VariantPage.tsx +++ b/apps/platform/src/pages/VariantPage/VariantPage.tsx @@ -1,4 +1,5 @@ -import { useState, useEffect, lazy, Suspense } from "react"; +import { Suspense } from "react"; +import { useQuery } from "@apollo/client"; import { useLocation, useParams, @@ -11,31 +12,20 @@ import { Box, Tabs, Tab } from "@mui/material"; import { BasePage, ScrollToTop, LoadingBackdrop } from "ui"; import Header from "./Header"; import NotFoundPage from "../NotFoundPage"; -import { MetadataType } from "./types"; - -const Profile = lazy(() => import("./Profile")); +import VARIANT_PAGE_QUERY from "./VariantPage.gql"; +import Profile from "./Profile"; function VariantPage() { const location = useLocation(); const { varId } = useParams() as { varId: string }; const { path } = useRouteMatch(); - // temp: data will come from gql, fetch local json file for now - const [metadata, setMetadata] = useState("waiting"); - useEffect(() => { - fetch("../data/variant-data-fake.json") - .then(response => response.json()) - .then((allData: MetadataType[]) => setMetadata(allData.find(v => v.variantId === varId))); - }, []); - - // temp: loading is set by useQuery, set to false for now - const loading = false; + const { loading, data } = useQuery(VARIANT_PAGE_QUERY, { + variables: { variantId: varId }, + }); - // temp: revisit this (use same as other pages) once using gql to get data - if (!metadata) { + if (data && !data.variant) { return ; - } else if (metadata === "waiting") { - return Waiting; } return ( @@ -44,7 +34,11 @@ function VariantPage() { description={`Annotation information for ${varId}`} location={location} > -
+
({ type XRefLinksProps = { label: string; + urlBuilder?: (id: string) => string; urlStem: string; ids: string[]; limit: number; }; -function XRefLinks({ label, urlStem, ids, limit }: XRefLinksProps) { +function XRefLinks({ label, urlBuilder, urlStem, ids, limit }: XRefLinksProps) { const [showMore, setShowMore] = useState(false); const classes = useStyles(); const displayNone = { @@ -29,10 +30,13 @@ function XRefLinks({ label, urlStem, ids, limit }: XRefLinksProps) { {label}:{" "} {ids.map((id, i) => ( limit - 1 && !showMore ? displayNone : {}}> - + {id} - {i < ids.length - 1 ? ", " : ""} + {i < ids.length - 1 ? ", " : ""} ))} {ids.length > limit ? ( From 381cc8c3d949fbf3d2484859ddc72b09c3559f3d Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Thu, 18 Jul 2024 17:49:25 +0100 Subject: [PATCH 12/17] [Platform] Correct dbXref link in variant page header (#414) --- apps/platform/src/pages/VariantPage/Header.tsx | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/apps/platform/src/pages/VariantPage/Header.tsx b/apps/platform/src/pages/VariantPage/Header.tsx index f70665d39..96da76299 100644 --- a/apps/platform/src/pages/VariantPage/Header.tsx +++ b/apps/platform/src/pages/VariantPage/Header.tsx @@ -3,7 +3,7 @@ import { Header as HeaderBase, XRefLinks } from "ui"; import { VariantPageDataType } from "./types"; const xrefsToDisplay = { - ensemblVariation: { + ensembl_variation: { label: "Ensembl", urlStem: "https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=", }, From eaeefb1902ce4fb8efde42bbe3056cc1514a1ece Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Mon, 22 Jul 2024 17:03:08 +0100 Subject: [PATCH 13/17] [Platform] Fix clinvar dbXref (#417) --- apps/platform/src/pages/VariantPage/Header.tsx | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/apps/platform/src/pages/VariantPage/Header.tsx b/apps/platform/src/pages/VariantPage/Header.tsx index 96da76299..ba754f1de 100644 --- a/apps/platform/src/pages/VariantPage/Header.tsx +++ b/apps/platform/src/pages/VariantPage/Header.tsx @@ -20,7 +20,7 @@ const xrefsToDisplay = { }&alternative_allele=${alternateAllele}` ), }, - clinVar: { + clinvar: { label: "ClinVar", urlStem: "https://www.ncbi.nlm.nih.gov/clinvar/variation/", }, From 967a05c1ee5b7f9598cbe9bc75a799322eec4463 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Mon, 22 Jul 2024 17:04:55 +0100 Subject: [PATCH 14/17] [Platform] Use API for metadata in variant page (#420) --- apps/platform/src/client.js | 3 + .../src/pages/VariantPage/Profile.tsx | 93 ++++++++++++------- .../src/pages/VariantPage/ProfileHeader.gql | 14 +++ .../src/pages/VariantPage/ProfileHeader.tsx | 75 +++++++-------- apps/platform/src/possibleTypes.json | 2 +- .../ui/src/contexts/PlatformApiProvider.jsx | 1 + 6 files changed, 115 insertions(+), 73 deletions(-) create mode 100644 apps/platform/src/pages/VariantPage/ProfileHeader.gql diff --git a/apps/platform/src/client.js b/apps/platform/src/client.js index 8d743ffc4..3d44db286 100644 --- a/apps/platform/src/client.js +++ b/apps/platform/src/client.js @@ -19,6 +19,9 @@ const client = new ApolloClient({ Hallmarks: { keyFields: [], }, + AlleleFrequency: { + keyFields: ["populationName"], + }, }, }), headers: { "OT-Platform": true }, diff --git a/apps/platform/src/pages/VariantPage/Profile.tsx b/apps/platform/src/pages/VariantPage/Profile.tsx index 407445f56..fe8c28a12 100644 --- a/apps/platform/src/pages/VariantPage/Profile.tsx +++ b/apps/platform/src/pages/VariantPage/Profile.tsx @@ -1,59 +1,82 @@ import { Suspense, lazy } from "react"; +import { gql } from "@apollo/client"; import { - // PlatformApiProvider, + PlatformApiProvider, SectionContainer, SummaryContainer, SectionLoader, + summaryUtils, } from "ui"; -import InSilicoPredictorsSummary from "sections/src/variant/InSilicoPredictors/Summary"; -import EVASummary from "sections/src/variant/EVA/Summary"; -import UniProtVariantsSummary from "sections/src/variant/UniProtVariants/Summary"; -import QTLCredibleSetsSummary from "sections/src/variant/QTLCredibleSets/Summary"; -import GWASCredibleSetsSummary from "sections/src/variant/GWASCredibleSets/Summary"; -import PharmacogenomicsSummary from "sections/src/variant/Pharmacogenomics/Summary"; +// import InSilicoPredictorsSummary from "sections/src/variant/InSilicoPredictors/Summary"; +// import EVASummary from "sections/src/variant/EVA/Summary"; +// import UniProtVariantsSummary from "sections/src/variant/UniProtVariants/Summary"; +// import QTLCredibleSetsSummary from "sections/src/variant/QTLCredibleSets/Summary"; +// import GWASCredibleSetsSummary from "sections/src/variant/GWASCredibleSets/Summary"; +// import PharmacogenomicsSummary from "sections/src/variant/Pharmacogenomics/Summary"; +import client from "../../client"; import ProfileHeader from "./ProfileHeader"; -const InSilicoPredictorsSection = lazy(() => import("sections/src/variant/InSilicoPredictors/Body")); -const EVASection = lazy(() => import("sections/src/variant/EVA/Body")); -const UniProtVariantsSection = lazy(() => import("sections/src/variant/UniProtVariants/Body")); -const QTLCredibleSetsSection = lazy(() => import("sections/src/variant/QTLCredibleSets/Body")); -const GWASCredibleSetsSection = lazy(() => import("sections/src/variant/GWASCredibleSets/Body")); -const PharmacogenomicsSection = lazy(() => import("sections/src/variant/Pharmacogenomics/Body")); +// const InSilicoPredictorsSection = lazy(() => import("sections/src/variant/InSilicoPredictors/Body")); +// const EVASection = lazy(() => import("sections/src/variant/EVA/Body")); +// const UniProtVariantsSection = lazy(() => import("sections/src/variant/UniProtVariants/Body")); +// const QTLCredibleSetsSection = lazy(() => import("sections/src/variant/QTLCredibleSets/Body")); +// const GWASCredibleSetsSection = lazy(() => import("sections/src/variant/GWASCredibleSets/Body")); +// const PharmacogenomicsSection = lazy(() => import("sections/src/variant/Pharmacogenomics/Body")); const summaries = [ - InSilicoPredictorsSummary, - EVASummary, - UniProtVariantsSummary, - QTLCredibleSetsSummary, - GWASCredibleSetsSummary, - PharmacogenomicsSummary, + // InSilicoPredictorsSummary, + // EVASummary, + // UniProtVariantsSummary, + // QTLCredibleSetsSummary, + // GWASCredibleSetsSummary, + // PharmacogenomicsSummary, ]; -const VARIANT = "variant"; +// const VARIANT = "variant"; +// const VARIANT_PROFILE_SUMMARY_FRAGMENT = summaryUtils.createSummaryFragment(summaries, "Variant"); +// const VARIANT_PROFILE_QUERY = gql` +// query VariantProfileQuery($variantId: String!) { +// variant(variantId: $variantId) { +// variantId +// ...VariantProfileHeaderFragment +// ...VariantProfileSummaryFragment +// } +// } +// ${ProfileHeader.fragments.profileHeader} +// ${VARIANT_PROFILE_SUMMARY_FRAGMENT} +// `; -// !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! -// TO DO (see e.g. profile.jsx for the evidence page): -// - VARIANT_PROFILE_SUMMARY_FRAGMENT -// - EVIDENCE_PROFILE_QUERY -// !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! +const VARIANT = "variant"; +const VARIANT_PROFILE_QUERY = gql` + query VariantProfileQuery($variantId: String!) { + variant(variantId: $variantId) { + variantId + ...VariantProfileHeaderFragment + } + } + ${ProfileHeader.fragments.profileHeader} +`; type ProfileProps = { varId: string; }; function Profile({ varId }: ProfileProps) { - + return ( - // !!!!!!!!!! - // PUT EVERYTHING INSIDE INSTEAD OF FRAGMENT - // !!!!!!!!!! - <> + + - + - + {/* @@ -61,7 +84,7 @@ function Profile({ varId }: ProfileProps) { - + }> @@ -81,9 +104,9 @@ function Profile({ varId }: ProfileProps) { }> - + */} - + ); diff --git a/apps/platform/src/pages/VariantPage/ProfileHeader.gql b/apps/platform/src/pages/VariantPage/ProfileHeader.gql new file mode 100644 index 000000000..5048dbdaa --- /dev/null +++ b/apps/platform/src/pages/VariantPage/ProfileHeader.gql @@ -0,0 +1,14 @@ +fragment VariantProfileHeaderFragment on VariantIndex { + chromosome + position + referenceAllele + alternateAllele + alleleFrequencies { + populationName + alleleFrequency + } + mostSevereConsequence { + id + label + } +} diff --git a/apps/platform/src/pages/VariantPage/ProfileHeader.tsx b/apps/platform/src/pages/VariantPage/ProfileHeader.tsx index 7615758c8..a3124eebe 100644 --- a/apps/platform/src/pages/VariantPage/ProfileHeader.tsx +++ b/apps/platform/src/pages/VariantPage/ProfileHeader.tsx @@ -1,32 +1,22 @@ -import { useState, useEffect } from "react"; -import { Field, ProfileHeader as BaseProfileHeader } from "ui"; +// import { useState, useEffect } from "react"; +import { + usePlatformApi, + Field, + ProfileHeader as BaseProfileHeader, + Link, +} from "ui"; import { Box, Typography } from "@mui/material"; +import { identifiersOrgLink } from "../../utils/global"; -type ProfileHeaderProps = { - varId: string; -}; +import VARIANT_PROFILE_HEADER_FRAGMENT from "./ProfileHeader.gql"; -function ProfileHeader({ varId }: ProfileHeaderProps) { - // temp: data will come from gql, fetch local json file for now - const [metadata, setMetadata] = - useState("waiting"); - useEffect(() => { - fetch("../data/variant-data-fake.json") - .then(response => response.json()) - .then((allData: MetadataType[]) => - setMetadata(allData.find(v => v.variantId === varId))); - }, []); +function ProfileHeader() { - // temp: always set loading to false for now - const loading = false; + const { loading, error, data } = usePlatformApi(); - // temp: revisit this (use same as other pages) once using gql to get data - if (!metadata) { - return Metadata not found! - } else if (metadata === "waiting") { - return Waiting; - } + // TODO: Errors! + if (error) return null; return ( @@ -34,43 +24,54 @@ function ProfileHeader({ varId }: ProfileHeaderProps) { Location - {metadata.chromosome}:{metadata.position} + {data?.variant.chromosome}:{data?.variant.position} - {metadata.referenceAllele} + {data?.variant.referenceAllele} - {metadata.alternateAllele} + {data?.variant.alternateAllele} Variant Effect Predictor (VEP) - - {metadata.vep.mostSevereConsequence.replace(/_/g, ' ')} + + + {data?.variant.mostSevereConsequence.label.replace(/_/g, ' ')} + - - Population Allele Frequencies - - + {data?.variant.alleleFrequencies.length > 0 && + + Population Allele Frequencies + + + } ) } +ProfileHeader.fragments = { + profileHeader: VARIANT_PROFILE_HEADER_FRAGMENT, +}; + export default ProfileHeader; -// THESE NEED CHECKED!! + +// ===================== +// allele frequency plot +// ===================== + const populationLabels = { - // from AB (orig from YT) afr_adj: "African-American", amr_adj: "American Admixed/Latino", asj_adj: "Ashkenazi Jewish", eas_adj: "East Asian", fin_adj: "Finnish", nfe_adj: "Non-Finnish European", - // nwe_adj: "Northwestern European", - // seu_adj: "Southeastern European", - // add in missing from above - ami_adj: "Amish", // from https://www.pharmgkb.org/variant/PA166175994 mid_adj: "Middle Eastern", // guessed from: https://gnomad.broadinstitute.org/variant/1-154453788-C-T?dataset=gnomad_r4 sas_adj: "South Asian", // from https://www.pharmgkb.org/variant/PA166175994 diff --git a/apps/platform/src/possibleTypes.json b/apps/platform/src/possibleTypes.json index 4276fdc50..89a5435be 100644 --- a/apps/platform/src/possibleTypes.json +++ b/apps/platform/src/possibleTypes.json @@ -1 +1 @@ -{"EntityUnionType":["Target","Drug","Disease"]} \ No newline at end of file +{"EntityUnionType":["Target", "Drug", "Disease", "VariantIndex"]} \ No newline at end of file diff --git a/packages/ui/src/contexts/PlatformApiProvider.jsx b/packages/ui/src/contexts/PlatformApiProvider.jsx index 619d6fbb3..3cf0b49ac 100644 --- a/packages/ui/src/contexts/PlatformApiProvider.jsx +++ b/packages/ui/src/contexts/PlatformApiProvider.jsx @@ -6,6 +6,7 @@ import { useQuery } from "@apollo/client"; const PlatformApiContext = createContext(); function PlatformApiProvider({ entity, lsSectionsField, query, client, variables, children }) { + const request = useQuery(query, { client, variables }); const platformApiValue = useMemo( From 33c08fe913d56a7039487445dc8dc224430566e7 Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Wed, 24 Jul 2024 10:42:59 +0100 Subject: [PATCH 15/17] [Platform] Use API data for in silico predictors widget on variant page (#424) Co-authored-by: Carlos Cruz --- apps/platform/src/client.js | 3 + .../src/pages/VariantPage/Profile.tsx | 50 +++++------ .../src/variant/InSilicoPredictors/Body.tsx | 85 +++++-------------- .../InSilicoPredictors/Description.tsx | 4 + .../InSilicoPredictorsQuery.gql | 11 +++ .../InSilicoPredictorsSummaryFragment.gql | 5 ++ .../variant/InSilicoPredictors/Summary.tsx | 28 ++---- .../src/variant/InSilicoPredictors/index.ts | 6 +- 8 files changed, 68 insertions(+), 124 deletions(-) create mode 100644 packages/sections/src/variant/InSilicoPredictors/InSilicoPredictorsQuery.gql create mode 100644 packages/sections/src/variant/InSilicoPredictors/InSilicoPredictorsSummaryFragment.gql diff --git a/apps/platform/src/client.js b/apps/platform/src/client.js index 3d44db286..9b4903125 100644 --- a/apps/platform/src/client.js +++ b/apps/platform/src/client.js @@ -22,6 +22,9 @@ const client = new ApolloClient({ AlleleFrequency: { keyFields: ["populationName"], }, + InSilicoPredictor: { + keyFields: ["method"], + }, }, }), headers: { "OT-Platform": true }, diff --git a/apps/platform/src/pages/VariantPage/Profile.tsx b/apps/platform/src/pages/VariantPage/Profile.tsx index fe8c28a12..3ecc25535 100644 --- a/apps/platform/src/pages/VariantPage/Profile.tsx +++ b/apps/platform/src/pages/VariantPage/Profile.tsx @@ -8,7 +8,7 @@ import { summaryUtils, } from "ui"; -// import InSilicoPredictorsSummary from "sections/src/variant/InSilicoPredictors/Summary"; +import InSilicoPredictorsSummary from "sections/src/variant/InSilicoPredictors/Summary"; // import EVASummary from "sections/src/variant/EVA/Summary"; // import UniProtVariantsSummary from "sections/src/variant/UniProtVariants/Summary"; // import QTLCredibleSetsSummary from "sections/src/variant/QTLCredibleSets/Summary"; @@ -18,7 +18,9 @@ import { import client from "../../client"; import ProfileHeader from "./ProfileHeader"; -// const InSilicoPredictorsSection = lazy(() => import("sections/src/variant/InSilicoPredictors/Body")); +const InSilicoPredictorsSection = lazy( + () => import("sections/src/variant/InSilicoPredictors/Body") +); // const EVASection = lazy(() => import("sections/src/variant/EVA/Body")); // const UniProtVariantsSection = lazy(() => import("sections/src/variant/UniProtVariants/Body")); // const QTLCredibleSetsSection = lazy(() => import("sections/src/variant/QTLCredibleSets/Body")); @@ -26,7 +28,7 @@ import ProfileHeader from "./ProfileHeader"; // const PharmacogenomicsSection = lazy(() => import("sections/src/variant/Pharmacogenomics/Body")); const summaries = [ - // InSilicoPredictorsSummary, + InSilicoPredictorsSummary, // EVASummary, // UniProtVariantsSummary, // QTLCredibleSetsSummary, @@ -34,29 +36,21 @@ const summaries = [ // PharmacogenomicsSummary, ]; -// const VARIANT = "variant"; -// const VARIANT_PROFILE_SUMMARY_FRAGMENT = summaryUtils.createSummaryFragment(summaries, "Variant"); -// const VARIANT_PROFILE_QUERY = gql` -// query VariantProfileQuery($variantId: String!) { -// variant(variantId: $variantId) { -// variantId -// ...VariantProfileHeaderFragment -// ...VariantProfileSummaryFragment -// } -// } -// ${ProfileHeader.fragments.profileHeader} -// ${VARIANT_PROFILE_SUMMARY_FRAGMENT} -// `; - const VARIANT = "variant"; +const VARIANT_PROFILE_SUMMARY_FRAGMENT = summaryUtils.createSummaryFragment( + summaries, + "VariantIndex" +); const VARIANT_PROFILE_QUERY = gql` query VariantProfileQuery($variantId: String!) { variant(variantId: $variantId) { variantId ...VariantProfileHeaderFragment + ...VariantIndexProfileSummaryFragment } } ${ProfileHeader.fragments.profileHeader} + ${VARIANT_PROFILE_SUMMARY_FRAGMENT} `; type ProfileProps = { @@ -64,32 +58,29 @@ type ProfileProps = { }; function Profile({ varId }: ProfileProps) { - return ( - - - {/* + - + {/* - + */} }> - + - }> + {/* }> }> @@ -103,13 +94,10 @@ function Profile({ varId }: ProfileProps) { }> - - */} - + */} + - ); - } -export default Profile; \ No newline at end of file +export default Profile; diff --git a/packages/sections/src/variant/InSilicoPredictors/Body.tsx b/packages/sections/src/variant/InSilicoPredictors/Body.tsx index a618f622a..41b37f29d 100644 --- a/packages/sections/src/variant/InSilicoPredictors/Body.tsx +++ b/packages/sections/src/variant/InSilicoPredictors/Body.tsx @@ -1,15 +1,12 @@ -// import { useQuery } from "@apollo/client"; +import { useQuery } from "@apollo/client"; import { Typography } from "@mui/material"; -import { Link, SectionItem, Tooltip, PublicationsDrawer, DataTable } from "ui"; +import { SectionItem, Tooltip, DataTable } from "ui"; import { definition } from "../InSilicoPredictors"; import Description from "../InSilicoPredictors/Description"; -import { epmcUrl } from "../../utils/urls"; -import { identifiersOrgLink } from "../../utils/global"; -import { defaultRowsPerPageOptions, naLabel, sectionsBaseSizeQuery, -} from "../../constants"; -// import UNIPROT_VARIANTS_QUERY from "./UniprotVariantsQuery.gql"; +import { defaultRowsPerPageOptions, naLabel } from "../../constants"; +import IN_SILICO_PREDICTORS_QUERY from "./InSilicoPredictorsQuery.gql"; -function getColumns(label: string) { +function getColumns() { return [ { id: "method", @@ -18,14 +15,14 @@ function getColumns(label: string) { { id: "assessment", label: "Prediction", - renderCell: ({ assessment, flag }) => ( - flag + renderCell: ({ assessment, assessmentFlag }) => ( + assessmentFlag ? ( - Flag: {flag} + Flag: {assessmentFlag} } @@ -47,25 +44,20 @@ function getColumns(label: string) { type BodyProps = { id: string, - label: string, entity: string, }; +export function Body({ id, entity }: BodyProps) { -export function Body({ id, label, entity }) { - - // const variables = { - // ensemblId: ensgId, - // efoId, - // size: sectionsBaseSizeQuery, - // }; + const variables = { + variantId: id, + }; - const columns = getColumns(label); + const columns = getColumns(); - // const request = useQuery(UNIPROT_VARIANTS_QUERY, { - // variables, - // }); - const request = mockQuery(); + const request = useQuery(IN_SILICO_PREDICTORS_QUERY, { + variables, + }); return ( } renderBody={() => { - // const rows = request.data.variant.inSilicoPredictors; const rows = [...request.data.variant.inSilicoPredictors].sort((row1, row2) => { return row1.method.localeCompare(row2.method); @@ -85,8 +76,8 @@ export function Body({ id, label, entity }) { rows={rows} dataDownloader rowsPerPageOptions={defaultRowsPerPageOptions} - // query={UNIPROT_VARIANTS_QUERY.loc.source.body} - // variables={variables} + query={IN_SILICO_PREDICTORS_QUERY.loc.source.body} + variables={variables} /> ); }} @@ -94,42 +85,4 @@ export function Body({ id, label, entity }) { ); } -export default Body; - -function mockQuery() { - return { - loading: false, - error: undefined, - data: JSON.parse(` -{ - "variant": { - "inSilicoPredictors": [ - { - "method": "alphaMissense", - "score": 0.077, - "assessment": "likely_benign" - }, - { - "method": "phred scaled CADD", - "score": 7.293 - }, - { - "method": "sift max", - "score": 0.2, - "assessment": "MODERATE" - }, - { - "method": "polyphen max", - "score": 0.069, - "assessment": "tolerated" - }, - { - "method": "loftee", - "assessment": "high-confidence LoF variant", - "flag": "PHYLOCSF_WEAK" - } - ] - } -}`), - }; -} +export default Body; \ No newline at end of file diff --git a/packages/sections/src/variant/InSilicoPredictors/Description.tsx b/packages/sections/src/variant/InSilicoPredictors/Description.tsx index 7125d6ea3..fded8a33c 100644 --- a/packages/sections/src/variant/InSilicoPredictors/Description.tsx +++ b/packages/sections/src/variant/InSilicoPredictors/Description.tsx @@ -11,6 +11,10 @@ function Description({ variantId }: DescriptionProps) { VEP + ,{" "} + + gnomAD + ); } diff --git a/packages/sections/src/variant/InSilicoPredictors/InSilicoPredictorsQuery.gql b/packages/sections/src/variant/InSilicoPredictors/InSilicoPredictorsQuery.gql new file mode 100644 index 000000000..3fd7babd8 --- /dev/null +++ b/packages/sections/src/variant/InSilicoPredictors/InSilicoPredictorsQuery.gql @@ -0,0 +1,11 @@ +query InSilicoPredictorsQuery($variantId: String!) { + variant(variantId: $variantId) { + variantId + inSilicoPredictors { + method + assessment + score + assessmentFlag + } + } +} \ No newline at end of file diff --git a/packages/sections/src/variant/InSilicoPredictors/InSilicoPredictorsSummaryFragment.gql b/packages/sections/src/variant/InSilicoPredictors/InSilicoPredictorsSummaryFragment.gql new file mode 100644 index 000000000..e5363eaa2 --- /dev/null +++ b/packages/sections/src/variant/InSilicoPredictors/InSilicoPredictorsSummaryFragment.gql @@ -0,0 +1,5 @@ +fragment InSilicoPredictorsSummaryFragment on VariantIndex { + inSilicoPredictors { + method + } +} \ No newline at end of file diff --git a/packages/sections/src/variant/InSilicoPredictors/Summary.tsx b/packages/sections/src/variant/InSilicoPredictors/Summary.tsx index 266cbf62d..4a7900864 100644 --- a/packages/sections/src/variant/InSilicoPredictors/Summary.tsx +++ b/packages/sections/src/variant/InSilicoPredictors/Summary.tsx @@ -1,35 +1,19 @@ import { SummaryItem, usePlatformApi } from "ui"; import { definition } from "."; -import { dataTypesMap } from "../../dataTypes"; -// import UNIPROT_VARIANTS_SUMMARY from "./UniprotVariantsSummaryQuery.gql"; +import IN_SILICO_PREDICTORS_SUMMARY from "./InSilicoPredictorsSummaryFragment.gql"; function Summary() { - // !! USE PLACEHOLDER REQUEST FOR NOW !! - // const request = usePlatformApi(UNIPROT_VARIANTS_SUMMARY); - const request = { - loading: false, - error: undefined, - data: true, // data is not actually used by summary - only cares if there is data - }; + const request = usePlatformApi(IN_SILICO_PREDICTORS_SUMMARY); return ( - {}} // !! renderSummary PROP NOT USED ANYMORE ANYWAY? - // renderSummary={({ uniprotVariantsSummary }) => { - // const { count } = uniprotVariantsSummary; - // return `${count} ${count === 1 ? "entry" : "entries"}`; - // }} - /> + ); } -// !!!!!!!!!!!!! -// Summary.fragments = { -// UniprotVariantsSummary: UNIPROT_VARIANTS_SUMMARY, -// }; +Summary.fragments = { + InSilicoPredictorsSummaryFragment: IN_SILICO_PREDICTORS_SUMMARY, +}; export default Summary; diff --git a/packages/sections/src/variant/InSilicoPredictors/index.ts b/packages/sections/src/variant/InSilicoPredictors/index.ts index 2b681c2fd..95b6cd008 100644 --- a/packages/sections/src/variant/InSilicoPredictors/index.ts +++ b/packages/sections/src/variant/InSilicoPredictors/index.ts @@ -1,11 +1,7 @@ -// import { isPrivateEvidenceSection } from "../../utils/partnerPreviewUtils"; - const id = "in_silico_predictors"; export const definition = { id, name: "In silico predictors", shortName: "VP", - // UPDATE HERE ONCE HAVE PROPER DATA - hasData: data => true, // data.uniprotVariantsSummary.count > 0, - isPrivate: false, // isPrivateEvidenceSection(id), + hasData: data => data?.inSilicoPredictors?.length > 0, }; From 3c0a399674e73bae8d7d25f6aa6c1ecb34df006e Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Mon, 29 Jul 2024 11:49:41 +0100 Subject: [PATCH 16/17] [Platform] Minor improvements to variant page insilico predictors widget (#429) --- .../src/variant/InSilicoPredictors/Body.tsx | 75 +++++++++---------- 1 file changed, 36 insertions(+), 39 deletions(-) diff --git a/packages/sections/src/variant/InSilicoPredictors/Body.tsx b/packages/sections/src/variant/InSilicoPredictors/Body.tsx index 41b37f29d..c6e365e46 100644 --- a/packages/sections/src/variant/InSilicoPredictors/Body.tsx +++ b/packages/sections/src/variant/InSilicoPredictors/Body.tsx @@ -6,41 +6,40 @@ import Description from "../InSilicoPredictors/Description"; import { defaultRowsPerPageOptions, naLabel } from "../../constants"; import IN_SILICO_PREDICTORS_QUERY from "./InSilicoPredictorsQuery.gql"; -function getColumns() { - return [ - { - id: "method", - label: "Method", - }, - { - id: "assessment", - label: "Prediction", - renderCell: ({ assessment, assessmentFlag }) => ( - assessmentFlag - ? ( - - - Flag: {assessmentFlag} - - - } - showHelpIcon - > - {assessment ?? naLabel} - - ) : ( - assessment ?? naLabel - ) - ) - }, - { - id: "score", - label: "Score", - }, - ]; -} +const columns = [ + { + id: "method", + label: "Method", + }, + { + id: "assessment", + label: "Prediction", + renderCell: ({ assessment, assessmentFlag }) => ( + assessmentFlag + ? ( + + + Flag: {assessmentFlag} + + + } + showHelpIcon + > + {assessment ?? naLabel} + + ) : ( + assessment ?? naLabel + ) + ) + }, + { + id: "score", + label: "Score", + renderCell: ({ score }) => score ?? naLabel, + }, +]; type BodyProps = { id: string, @@ -53,8 +52,6 @@ export function Body({ id, entity }: BodyProps) { variantId: id, }; - const columns = getColumns(); - const request = useQuery(IN_SILICO_PREDICTORS_QUERY, { variables, }); @@ -65,9 +62,9 @@ export function Body({ id, entity }: BodyProps) { request={request} entity={entity} renderDescription={() => } - renderBody={() => { + renderBody={({ variant }) => { const rows = - [...request.data.variant.inSilicoPredictors].sort((row1, row2) => { + [...variant.inSilicoPredictors].sort((row1, row2) => { return row1.method.localeCompare(row2.method); }); return ( From a868b35b93cce9960ca907239fd46b848de6b05e Mon Sep 17 00:00:00 2001 From: Graham McNeill Date: Mon, 29 Jul 2024 14:47:22 +0100 Subject: [PATCH 17/17] [Platform] Add VEP widget to variant page (#428) --- .../src/pages/VariantPage/Profile.tsx | 20 ++- .../variant/VariantEffectPredictor/Body.tsx | 164 ++++++++++++++++++ .../VariantEffectPredictor/Description.tsx | 18 ++ .../VariantEffectPredictor/Summary.tsx | 19 ++ .../VariantEffectPredictorQuery.gql | 23 +++ .../VariantEffectPredictorSummaryFragment.gql | 5 + .../variant/VariantEffectPredictor/index.ts | 7 + 7 files changed, 249 insertions(+), 7 deletions(-) create mode 100644 packages/sections/src/variant/VariantEffectPredictor/Body.tsx create mode 100644 packages/sections/src/variant/VariantEffectPredictor/Description.tsx create mode 100644 packages/sections/src/variant/VariantEffectPredictor/Summary.tsx create mode 100644 packages/sections/src/variant/VariantEffectPredictor/VariantEffectPredictorQuery.gql create mode 100644 packages/sections/src/variant/VariantEffectPredictor/VariantEffectPredictorSummaryFragment.gql create mode 100644 packages/sections/src/variant/VariantEffectPredictor/index.ts diff --git a/apps/platform/src/pages/VariantPage/Profile.tsx b/apps/platform/src/pages/VariantPage/Profile.tsx index 3ecc25535..2e967ad0a 100644 --- a/apps/platform/src/pages/VariantPage/Profile.tsx +++ b/apps/platform/src/pages/VariantPage/Profile.tsx @@ -9,6 +9,7 @@ import { } from "ui"; import InSilicoPredictorsSummary from "sections/src/variant/InSilicoPredictors/Summary"; +import VariantEffectPredictorSummary from "sections/src/variant/VariantEffectPredictor/Summary"; // import EVASummary from "sections/src/variant/EVA/Summary"; // import UniProtVariantsSummary from "sections/src/variant/UniProtVariants/Summary"; // import QTLCredibleSetsSummary from "sections/src/variant/QTLCredibleSets/Summary"; @@ -18,9 +19,8 @@ import InSilicoPredictorsSummary from "sections/src/variant/InSilicoPredictors/S import client from "../../client"; import ProfileHeader from "./ProfileHeader"; -const InSilicoPredictorsSection = lazy( - () => import("sections/src/variant/InSilicoPredictors/Body") -); +const InSilicoPredictorsSection = lazy(() => import("sections/src/variant/InSilicoPredictors/Body")); +const VariantEffectPredictorSection = lazy(() => import("sections/src/variant/VariantEffectPredictor/Body")); // const EVASection = lazy(() => import("sections/src/variant/EVA/Body")); // const UniProtVariantsSection = lazy(() => import("sections/src/variant/UniProtVariants/Body")); // const QTLCredibleSetsSection = lazy(() => import("sections/src/variant/QTLCredibleSets/Body")); @@ -29,6 +29,7 @@ const InSilicoPredictorsSection = lazy( const summaries = [ InSilicoPredictorsSummary, + VariantEffectPredictorSummary, // EVASummary, // UniProtVariantsSummary, // QTLCredibleSetsSummary, @@ -37,10 +38,7 @@ const summaries = [ ]; const VARIANT = "variant"; -const VARIANT_PROFILE_SUMMARY_FRAGMENT = summaryUtils.createSummaryFragment( - summaries, - "VariantIndex" -); +const VARIANT_PROFILE_SUMMARY_FRAGMENT = summaryUtils.createSummaryFragment(summaries, "VariantIndex"); const VARIANT_PROFILE_QUERY = gql` query VariantProfileQuery($variantId: String!) { variant(variantId: $variantId) { @@ -58,7 +56,9 @@ type ProfileProps = { }; function Profile({ varId }: ProfileProps) { + return ( + + {/* @@ -80,6 +81,9 @@ function Profile({ varId }: ProfileProps) { }> + }> + + {/* }> @@ -96,7 +100,9 @@ function Profile({ varId }: ProfileProps) { */} + + ); } diff --git a/packages/sections/src/variant/VariantEffectPredictor/Body.tsx b/packages/sections/src/variant/VariantEffectPredictor/Body.tsx new file mode 100644 index 000000000..28bad5cff --- /dev/null +++ b/packages/sections/src/variant/VariantEffectPredictor/Body.tsx @@ -0,0 +1,164 @@ +import { useQuery } from "@apollo/client"; +import { Link, SectionItem, DataTable } from "ui"; +import { Fragment } from "react"; +import { definition } from "../VariantEffectPredictor"; +import Description from "../VariantEffectPredictor/Description"; +import { defaultRowsPerPageOptions, naLabel } from "../../constants"; +import { identifiersOrgLink } from "../../utils/global"; +import VARIANT_EFFECT_PREDICTOR_QUERY from "./VariantEffectPredictorQuery.gql"; + +function formatVariantConsequenceLabel(label) { + return label.replace(/_/g, ' '); +} + +const columns = [ + { + id: "transcriptId", + label: "Transcript", + tooltip: "Ensembl canonical transcript", + renderCell: ({ transcriptId, target }) => { + if (!transcriptId) return naLabel; + if (!target) return transcriptId; + return ( + + {transcriptId} + + ) + } + }, + { + id: "variantConsequences.label", + label: "Predicted consequence", + renderCell: ({ variantConsequences }) => ( + variantConsequences.length + ? variantConsequences.map(({ id, label }, i, arr) => ( + + + {formatVariantConsequenceLabel(label)} + + {i < arr.length - 1 && ", "} + + )) + : naLabel + ), + exportValue: ({ variantConsequences }) => { + return variantConsequences.map(({ label }) => { + return formatVariantConsequenceLabel(label) + }).join(", ") + }, + }, + { + id: 'impact', + label: 'Impact', + renderCell: ({ impact }) => impact?.toLowerCase?.() ?? naLabel, + }, + { // !!!!! UPDATE ONCE IN API + id: "consequenceScore", + label: "Consequence Score", + renderCell: () => "Not in API" + }, + { + id: "target.approvedName", + label: "Gene", + renderCell: ({ target }) => ( + target + ? {target.approvedName} + : naLabel + ), + }, + { + id: 'aminoAcidChange', + label: 'Amino acid change', + renderCell: ({ aminoAcidChange }) => aminoAcidChange ?? naLabel, + }, + { + id: 'codons', + label: 'Coding change', + renderCell: ({ codons }) => codons ?? naLabel, + }, + { // !!!!! UPDATE ONCE IN API - AND DIST SHOULD BE 0 IN DATA THEN INSTEAD OF NULL + id: "distance", + label: "Distance from footprint", + renderCell: ({ distance }) => distance ?? 0, + }, + { // !!!!! UPDATE ONCE IN API + id: "distanceFromTss", + label: "Distance from start site", + renderCell: () => "Not in API", + }, + { + id: "lofteePrediction", + label: "Loftee prediction", + renderCell: ({ lofteePrediction }) => lofteePrediction ?? naLabel, + }, + { + id: "siftPrediction", + label: "Sift prediction", + renderCell: ({ siftPrediction }) => siftPrediction ?? naLabel, + }, + { + id: "polyphenPrediction", + label: "Polyphen prediction", + renderCell: ({ polyphenPrediction }) => polyphenPrediction ?? naLabel, + }, + { + id: "uniprotAccession", + label: "Uniprot accession", + renderCell: ({ uniprotAccessions }) => ( + uniprotAccessions?.length + ? uniprotAccessions.map((id, i, arr) => ( + + + {id} + + { i < arr.length - 1 && ", " } + + )) + : naLabel + ), + exportValue: ({ uniprotAccessions }) => (uniprotAccessions ?? []).join(", ") + } +]; + +type BodyProps = { + id: string, + entity: string, +}; + +export function Body({ id, entity }: BodyProps) { + + const variables = { + variantId: id, + }; + + const request = useQuery(VARIANT_EFFECT_PREDICTOR_QUERY, { + variables, + }); + + return ( + } + renderBody={({ variant }) => { + return ( + + ); + }} + /> + ); +} + +export default Body; \ No newline at end of file diff --git a/packages/sections/src/variant/VariantEffectPredictor/Description.tsx b/packages/sections/src/variant/VariantEffectPredictor/Description.tsx new file mode 100644 index 000000000..4c8afd132 --- /dev/null +++ b/packages/sections/src/variant/VariantEffectPredictor/Description.tsx @@ -0,0 +1,18 @@ +import { Link } from "ui"; + +type DescriptionProps = { + variantId: string; +}; + +function Description({ variantId }: DescriptionProps) { + return ( + <> + Variant consequence prediction for {variantId}. {" "}Source:{" "} + + VEP + + + ); +} + +export default Description; \ No newline at end of file diff --git a/packages/sections/src/variant/VariantEffectPredictor/Summary.tsx b/packages/sections/src/variant/VariantEffectPredictor/Summary.tsx new file mode 100644 index 000000000..34f4c85f5 --- /dev/null +++ b/packages/sections/src/variant/VariantEffectPredictor/Summary.tsx @@ -0,0 +1,19 @@ +import { SummaryItem, usePlatformApi } from "ui"; + +import { definition } from "."; +import VARIANT_EFFECT_PREDICTOR_SUMMARY from "./VariantEffectPredictorSummaryFragment.gql"; + +function Summary() { + + const request = usePlatformApi(VARIANT_EFFECT_PREDICTOR_SUMMARY); + + return ( + + ); +} + +Summary.fragments = { + VariantEffectPredictorSummaryFragment: VARIANT_EFFECT_PREDICTOR_SUMMARY, +}; + +export default Summary; diff --git a/packages/sections/src/variant/VariantEffectPredictor/VariantEffectPredictorQuery.gql b/packages/sections/src/variant/VariantEffectPredictor/VariantEffectPredictorQuery.gql new file mode 100644 index 000000000..5af09cf0f --- /dev/null +++ b/packages/sections/src/variant/VariantEffectPredictor/VariantEffectPredictorQuery.gql @@ -0,0 +1,23 @@ +query VariantEffectPredictorQuery($variantId: String!) { + variant(variantId: $variantId){ + transcriptConsequences { + variantConsequences { + id + label + } + aminoAcidChange + uniprotAccessions + codons + distance + target { + id + approvedName + } + impact + transcriptId + lofteePrediction + siftPrediction + polyphenPrediction + } + } +} \ No newline at end of file diff --git a/packages/sections/src/variant/VariantEffectPredictor/VariantEffectPredictorSummaryFragment.gql b/packages/sections/src/variant/VariantEffectPredictor/VariantEffectPredictorSummaryFragment.gql new file mode 100644 index 000000000..05d1b57fb --- /dev/null +++ b/packages/sections/src/variant/VariantEffectPredictor/VariantEffectPredictorSummaryFragment.gql @@ -0,0 +1,5 @@ +fragment VariantEffectPredictorSummaryFragment on VariantIndex { + transcriptConsequences { + isEnsemblCanonical + } +} \ No newline at end of file diff --git a/packages/sections/src/variant/VariantEffectPredictor/index.ts b/packages/sections/src/variant/VariantEffectPredictor/index.ts new file mode 100644 index 000000000..ac4c2a089 --- /dev/null +++ b/packages/sections/src/variant/VariantEffectPredictor/index.ts @@ -0,0 +1,7 @@ +const id = "variant_effect_predictor"; +export const definition = { + id, + name: "Variant Effect Predictor (VEP)", + shortName: "VE", + hasData: data => data?.transcriptConsequences?.length > 0, +};