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AnnotatorCore.py
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AnnotatorCore.py
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#!/usr/bin/python
import datetime
import json
import csv
import sys
import requests
import os.path
import logging
import re
import ctypes as ct
from enum import Enum
from requests.adapters import HTTPAdapter
from urllib3 import Retry
from datetime import date
logging.basicConfig(level=logging.INFO)
logging.getLogger("requests").setLevel(logging.WARNING)
logging.getLogger("urllib3").setLevel(logging.WARNING)
log = logging.getLogger('AnnotatorCore')
# API timeout is set to two minutes
REQUEST_TIMEOUT = 240
API_REQUEST_RETRY_STATUS_FORCELIST = [429, 500, 502, 503, 504]
csv.field_size_limit(int(ct.c_ulong(
-1).value // 2)) # Deal with overflow problem on Windows, https://stackoverflow.co/120m/questions/15063936/csv-error-field-larger-than-field-limit-131072
sizeLimit = csv.field_size_limit()
csv.field_size_limit(sizeLimit) # for reading large files
DEFAULT_ONCOKB_URL = "https://www.oncokb.org"
oncokb_api_url = DEFAULT_ONCOKB_URL + "/api"
oncokb_annotation_api_url = oncokb_api_url + "/v1"
oncokb_api_bearer_token = ""
# 'U', which no longer has any effect in python 3. 3.11 completely removed the option.
# It will throw error if we don't do condition check.
# https://stackoverflow.com/questions/56791545/what-is-the-non-deprecated-version-of-open-u-mode
DEFAULT_READ_FILE_MODE = 'r' if sys.version_info.major > 2 else 'rU'
def setoncokbbaseurl(u):
if u and u is not None:
global oncokb_api_url
global oncokb_annotation_api_url
oncokb_api_url = u.rstrip('/') + '/api'
oncokb_annotation_api_url = oncokb_api_url + '/v1'
def setoncokbapitoken(t):
global oncokb_api_bearer_token
oncokb_api_bearer_token = t.strip()
cancerhotspotsbaseurl = "http://www.cancerhotspots.org"
def setcancerhotspotsbaseurl(u):
global cancerhotspotsbaseurl
cancerhotspotsbaseurl = u
_3dhotspotsbaseurl = "http://www.3dhotspots.org"
def set3dhotspotsbaseurl(u):
global _3dhotspotsbaseurl
_3dhotspotsbaseurl = u
sampleidsfilter = None
def setsampleidsfileterfile(f):
global sampleidsfilter
content = [line.rstrip() for line in open(f)]
sampleidsfilter = set(content)
log.info(len(sampleidsfilter))
ANNOTATED_HEADER = 'ANNOTATED'
GENE_IN_ONCOKB_HEADER = 'GENE_IN_ONCOKB'
VARIANT_IN_ONCOKB_HEADER = 'VARIANT_IN_ONCOKB'
GENE_IN_ONCOKB_DEFAULT = 'False'
VARIANT_IN_ONCOKB_DEFAULT = 'False'
levels = [
'LEVEL_R1',
'LEVEL_1',
'LEVEL_2',
'LEVEL_3A',
'LEVEL_3B',
'LEVEL_4',
'LEVEL_R2'
]
sensitive_levels = [
'LEVEL_1',
'LEVEL_2',
'LEVEL_3A',
'LEVEL_3B',
'LEVEL_4',
]
resistance_levels = [
'LEVEL_R1',
'LEVEL_R2'
]
TX_TYPE_SENSITIVE = 'sensitive'
TX_TYPE_RESISTANCE = 'resistance'
dxLevels = [
'LEVEL_Dx1',
'LEVEL_Dx2',
'LEVEL_Dx3'
]
pxLevels = [
'LEVEL_Px1',
'LEVEL_Px2',
'LEVEL_Px3'
]
mutationtypeconsequencemap = {
'3\'Flank': ['any'],
'5\'Flank ': ['any'],
'Targeted_Region': ['inframe_deletion', 'inframe_insertion'],
'COMPLEX_INDEL': ['inframe_deletion', 'inframe_insertion'],
'ESSENTIAL_SPLICE_SITE': ['feature_truncation'],
'Exon skipping': ['inframe_deletion'],
'Frameshift deletion': ['frameshift_variant'],
'Frameshift insertion': ['frameshift_variant'],
'FRAMESHIFT_CODING': ['frameshift_variant'],
'Frame_Shift_Del': ['frameshift_variant'],
'Frame_Shift_Ins': ['frameshift_variant'],
'Fusion': ['fusion'],
'Indel': ['frameshift_variant', 'inframe_deletion', 'inframe_insertion'],
'In_Frame_Del': ['inframe_deletion'],
'In_Frame_Ins': ['inframe_insertion'],
'Missense': ['missense_variant'],
'Missense_Mutation': ['missense_variant'],
'Nonsense_Mutation': ['stop_gained'],
'Nonstop_Mutation': ['stop_lost'],
'Splice_Site': ['splice_region_variant'],
'Splice_Site_Del': ['splice_region_variant'],
'Splice_Site_SNP': ['splice_region_variant'],
'splicing': ['splice_region_variant'],
'Translation_Start_Site': ['start_lost'],
'vIII deletion': ['any']
}
CNA_AMPLIFICATION_TXT = 'Amplification'
CNA_DELETION_TXT = 'Deletion'
CNA_LOSS_TXT = 'Loss'
CNA_GAIN_TXT = 'Gain'
CNAS = [
CNA_DELETION_TXT,
CNA_LOSS_TXT,
CNA_GAIN_TXT,
CNA_AMPLIFICATION_TXT,
]
GISTIC_CNA_MAP = {
"-2": CNA_DELETION_TXT,
"-1.5": CNA_DELETION_TXT,
"-1": CNA_LOSS_TXT,
"1": CNA_GAIN_TXT,
"2": CNA_AMPLIFICATION_TXT
}
CNA_FILE_FORMAT_GISTIC = 'gistic'
CNA_FILE_FORMAT_INDIVIDUAL = 'individual'
CND_FILE_FORMAT = [CNA_FILE_FORMAT_GISTIC, CNA_FILE_FORMAT_INDIVIDUAL]
# column headers
HUGO_HEADERS = ['HUGO_SYMBOL', 'HUGO_GENE_SYMBOL', 'GENE']
CONSEQUENCE_HEADERS = ['VARIANT_CLASSIFICATION', 'MUTATION_TYPE']
ALTERATION_HEADER = 'ALTERATION'
HGVSP_SHORT_HEADER = 'HGVSP_SHORT'
HGVSP_HEADER = 'HGVSP'
HGVSG_HEADER = 'HGVSG'
# columns for copy number alteration
CNA_HEADERS = [ALTERATION_HEADER, 'COPY_NUMBER_ALTERATION', 'CNA', 'GISTIC']
HGVS_HEADERS = [ALTERATION_HEADER, HGVSP_SHORT_HEADER, HGVSP_HEADER, HGVSG_HEADER, 'AMINO_ACID_CHANGE',
'FUSION'] + CNA_HEADERS
SAMPLE_HEADERS = ['SAMPLE_ID', 'TUMOR_SAMPLE_BARCODE']
PROTEIN_START_HEADERS = ['PROTEIN_START']
PROTEIN_END_HEADERS = ['PROTEIN_END']
PROTEIN_POSITION_HEADERS = ['PROTEIN_POSITION']
CANCER_TYPE_HEADERS = ['ONCOTREE_CODE', 'CANCER_TYPE']
FUSION_HEADERS = ['FUSION']
REFERENCE_GENOME_HEADERS = ['NCBI_BUILD', 'REFERENCE_GENOME']
# columns for genomic change annotation
GC_CHROMOSOME_HEADER = 'CHROMOSOME'
GC_START_POSITION_HEADER = 'START_POSITION'
GC_END_POSITION_HEADER = 'END_POSITION'
GC_REF_ALLELE_HEADER = 'REFERENCE_ALLELE'
GC_VAR_ALLELE_1_HEADER = 'TUMOR_SEQ_ALLELE1'
GC_VAR_ALLELE_2_HEADER = 'TUMOR_SEQ_ALLELE2'
GENOMIC_CHANGE_HEADERS = [GC_CHROMOSOME_HEADER, GC_START_POSITION_HEADER, GC_END_POSITION_HEADER, GC_REF_ALLELE_HEADER,
GC_VAR_ALLELE_2_HEADER]
# columns for structural variant annotation
SV_GENEA_HEADER = ['SITE1_GENE', 'GENEA', 'GENE1', 'SITE1_HUGO_SYMBOL']
SV_GENEB_HEADER = ['SITE2_GENE', 'GENEB', 'GENE2', 'SITE2_HUGO_SYMBOL']
SV_TYPE_HEADER = ['SV_CLASS_NAME', 'SV_TYPE', 'CLASS']
SV_TYPES = ['DELETION', 'TRANSLOCATION', 'DUPLICATION', 'INSERTION', 'INVERSION', 'FUSION', 'UNKNOWN']
DESCRIPTION_HEADERS = ['GENE_SUMMARY', 'VARIANT_SUMMARY', 'TUMOR_TYPE_SUMMARY', 'DIAGNOSTIC_SUMMARY',
'PROGNOSTIC_SUMMARY', 'MUTATION_EFFECT_DESCRIPTION']
ONCOKB_ANNOTATION_HEADERS_GC = ["ONCOKB_HUGO_SYMBOL", "ONCOKB_PROTEIN_CHANGE", "ONCOKB_CONSEQUENCE"]
UNKNOWN = 'UNKNOWN'
class QueryType(Enum):
HGVSP_SHORT = 'HGVSP_SHORT'
HGVSP = 'HGVSP'
HGVSG = 'HGVSG'
GENOMIC_CHANGE = 'GENOMIC_CHANGE'
class ReferenceGenome(Enum):
GRCH37 = 'GRCh37'
GRCH38 = 'GRCh38'
REQUIRED_QUERY_TYPE_COLUMNS = {
QueryType.HGVSP_SHORT: [HGVSP_SHORT_HEADER],
QueryType.HGVSP: [HGVSP_HEADER],
QueryType.HGVSG: [HGVSG_HEADER],
QueryType.GENOMIC_CHANGE: GENOMIC_CHANGE_HEADERS
}
POST_QUERIES_THRESHOLD = 200
POST_QUERIES_THRESHOLD_GC_HGVSG = 100
def getOncokbInfo():
ret = ['Files annotated on ' + date.today().strftime('%m/%d/%Y') + "\nOncoKB API URL: " + oncokb_annotation_api_url]
try:
info = requests.get(oncokb_annotation_api_url + "/info", timeout=REQUEST_TIMEOUT).json()
ret.append(
'\nOncoKB data version: ' + info['dataVersion']['version'] + ', released on ' + info['dataVersion']['date'])
except Exception:
log.error("error when fetch OncoKB info")
return ''.join(ret)
def validate_oncokb_token():
if not oncokb_annotation_api_url.startswith(DEFAULT_ONCOKB_URL):
log.warning(
"OncoKB base url has been specified by the user that is different from the default www.oncokb.org. The token validation is skipped.")
return None
if oncokb_api_bearer_token is None or not oncokb_api_bearer_token:
log.error("Please specify your OncoKB token")
exit()
response = requests.get(oncokb_api_url + "/tokens/" + oncokb_api_bearer_token, timeout=REQUEST_TIMEOUT)
if response.status_code == 200:
token = response.json()
time_stamp = datetime.datetime.strptime(token['expiration'], "%Y-%m-%dT%H:%M:%SZ")
days_from_expiration = time_stamp - datetime.datetime.now()
if (days_from_expiration.days < 0):
log.error(
"Your OncoKB API token already expired. Please reach out to us to renew your token.")
exit()
elif (days_from_expiration.days < 7):
log.warning(
"Your OncoKB API token will expire soon, please be on the lookout for an OncoKB email to renew your token. Expire on " + str(
time_stamp) + ' UTC')
else:
log.info("Your OncoKB API token is valid and will expire on " + str(time_stamp) + ' UTC')
else:
try:
response_json = response.json()
reason = response_json["title"]
if response_json["detail"]:
reason = response_json["detail"]
except Exception:
reason = response.reason
log.error("Error when validating token, " + "reason: %s" % reason)
exit()
def generateReadme(outfile):
outf = open(outfile, 'w+', 1000)
outf.write(getOncokbInfo())
outf.close()
def gethotspots(url, type):
hotspots = {}
response = requests.get(url, timeout=REQUEST_TIMEOUT)
if response.status_code == 200:
hotspotsjson = response.json()
for hs in hotspotsjson:
gene = hs['hugoSymbol']
start = hs['aminoAcidPosition']['start']
end = hs['aminoAcidPosition']['end']
if type is None or hs['type'] == type:
if gene not in hotspots:
hotspots[gene] = set()
for i in range(start, end + 1):
hotspots[gene].add(i)
else:
log.error("error when processing %s \n" % url + "reason: %s" % response.reason)
return hotspots
def requests_retry_session(
retries=3,
backoff_factor=0.3,
status_forcelist=API_REQUEST_RETRY_STATUS_FORCELIST,
allowed_methods=('GET', 'HEAD'),
session=None,
):
session = session or requests.Session()
retry = Retry(
total=retries,
read=retries,
connect=retries,
backoff_factor=backoff_factor,
status_forcelist=status_forcelist,
allowed_methods=allowed_methods,
)
adapter = HTTPAdapter(max_retries=retry)
session.mount('http://', adapter)
session.mount('https://', adapter)
return session
def makeoncokbpostrequest(url, body):
headers = {
'Content-Type': 'application/json',
'Authorization': 'Bearer %s' % oncokb_api_bearer_token
}
return requests_retry_session(allowed_methods=["POST"]).post(url, headers=headers,
data=json.dumps(body, default=lambda o: o.__dict__),
timeout=REQUEST_TIMEOUT)
def makeoncokbgetrequest(url):
headers = {
'Content-Type': 'application/json',
'Authorization': 'Bearer %s' % oncokb_api_bearer_token
}
return requests_retry_session(allowed_methods=["HEAD", "GET"]).get(url, headers=headers, timeout=REQUEST_TIMEOUT)
_3dhotspots = None
def init_3d_hotspots():
global _3dhotspots
_3dhotspots = gethotspots(_3dhotspotsbaseurl + "/api/hotspots/3d", None)
conversiondict = {'Ala': 'A',
'Asx': 'B',
'Cys': 'C',
'Asp': 'D',
'Glu': 'E',
'Phe': 'F',
'Gly': 'G',
'His': 'H',
'Ile': 'I',
'Lys': 'K',
'Leu': 'L',
'Met': 'M',
'Asn': 'N',
'Pro': 'P',
'Gln': 'Q',
'Arg': 'R',
'Ser': 'S',
'Thr': 'T',
'Val': 'V',
'Trp': 'W',
'Tyr': 'Y',
'Glx': 'Z'
}
conversionlist = conversiondict.keys()
def conversion(hgvs):
threecharactersearch = re.findall(r'[a-zA-Z]{3}\d+', hgvs, flags=re.IGNORECASE)
if threecharactersearch:
if any(letters.lower() in hgvs.lower() for letters in conversionlist):
return replace_all(hgvs)
return hgvs
def replace_all(hgvs):
# Author: Thomas Glaessle
pattern = re.compile('|'.join(conversionlist), re.IGNORECASE)
return pattern.sub(lambda m: conversiondict[m.group().capitalize()], hgvs)
def append_annotation_to_file(outf, ncols, rows, annotations):
if len(rows) != len(annotations):
log.error('The length of the rows and annotations do not match')
for index, annotation in enumerate(annotations):
row = rows[index]
if annotation is not None:
row = row + annotation
row = padrow(row, ncols)
rowstr = '\t'.join(row)
rowstr = rowstr.encode('ascii', 'ignore').decode('ascii')
outf.write(rowstr + "\n")
def get_tumor_type_from_row(row, row_index, defaultCancerType, icancertype, cancerTypeMap, sample):
cancertype = defaultCancerType
if icancertype >= 0:
row_cancer_type = get_cell_content(row, icancertype)
if row_cancer_type is not None:
cancertype = row_cancer_type
if sample in cancerTypeMap:
cancertype = cancerTypeMap[sample]
if cancertype == "":
log.info(
"Cancer type for the sample should be defined for a more accurate result. \tLine %s" % (row_index))
# continue
return cancertype
def has_desired_headers(desired_headers, file_headers):
has_required_headers = True
for header in desired_headers:
if header not in file_headers:
has_required_headers = False
break
return has_required_headers
def resolve_query_type(user_input_query_type, headers):
selected_query_type = None
if isinstance(user_input_query_type, QueryType):
selected_query_type = user_input_query_type
if selected_query_type is None and HGVSP_SHORT_HEADER in headers:
selected_query_type = QueryType.HGVSP_SHORT
if selected_query_type is None and HGVSP_HEADER in headers:
selected_query_type = QueryType.HGVSP
if selected_query_type is None and HGVSG_HEADER in headers:
selected_query_type = QueryType.HGVSG
if selected_query_type is None and has_desired_headers(REQUIRED_QUERY_TYPE_COLUMNS[QueryType.GENOMIC_CHANGE],
headers):
selected_query_type = QueryType.GENOMIC_CHANGE
# default to HGVSp_Short
if selected_query_type is None:
selected_query_type = QueryType.HGVSP_SHORT
# check the file has required columns
if has_desired_headers(REQUIRED_QUERY_TYPE_COLUMNS[selected_query_type], headers) is False:
# when it is False, it will never be GENOMIC_CHANGE. For other types, we need to check whether ALTERATION column is available
if ALTERATION_HEADER not in headers:
raise Exception(
"The file does not have required columns "
+ ', '.join(REQUIRED_QUERY_TYPE_COLUMNS[user_input_query_type])
+ " for the query type: "
+ user_input_query_type.value
)
return selected_query_type
def get_reference_genome_from_row(row_reference_genome, default_reference_genome):
reference_genome = default_reference_genome
if row_reference_genome is not None and row_reference_genome != '':
try:
reference_genome = ReferenceGenome[row_reference_genome.upper()]
except KeyError:
log.warning('Unexpected reference genome, only GRCh37 and GRCh38 are supported.' + (
' Use default.' if default_reference_genome is not None else ' Skipping.'))
return reference_genome
def append_headers(outf, newncols, include_descriptions, genomic_change_annotation):
oncokb_annotation_headers = get_oncokb_annotation_column_headers(include_descriptions, genomic_change_annotation)
outf.write("\t".join(oncokb_annotation_headers))
newncols += len(oncokb_annotation_headers)
outf.write("\n")
return newncols
def processalterationevents(eventfile, outfile, previousoutfile, defaultCancerType, cancerTypeMap,
annotatehotspots, user_input_query_type, default_reference_genome, include_descriptions):
if annotatehotspots:
init_3d_hotspots()
if os.path.isfile(previousoutfile):
cacheannotated(previousoutfile, defaultCancerType, cancerTypeMap)
outf = open(outfile, 'w+', 1000)
with open(eventfile, DEFAULT_READ_FILE_MODE) as infile:
reader = csv.reader(infile, delimiter='\t')
headers = readheaders(reader)
ncols = headers["length"]
if ncols == 0:
return
newncols = 0
outf.write(headers['^-$'])
if annotatehotspots:
outf.write("\tIS-A-HOTSPOT")
outf.write("\tIS-A-3D-HOTSPOT")
newncols += 2
outf.write("\t")
query_type = resolve_query_type(user_input_query_type, headers)
if (query_type == QueryType.HGVSP_SHORT):
newncols = append_headers(outf, newncols, include_descriptions, False)
process_alteration(reader, outf, headers, [HGVSP_SHORT_HEADER, ALTERATION_HEADER], ncols, newncols,
defaultCancerType,
cancerTypeMap, annotatehotspots, default_reference_genome, include_descriptions)
if (query_type == QueryType.HGVSP):
newncols = append_headers(outf, newncols, include_descriptions, False)
process_alteration(reader, outf, headers, [HGVSP_HEADER, ALTERATION_HEADER], ncols, newncols,
defaultCancerType,
cancerTypeMap, annotatehotspots, default_reference_genome, include_descriptions)
if (query_type == QueryType.HGVSG):
newncols = append_headers(outf, newncols, include_descriptions, True)
process_hvsg(reader, outf, headers, [HGVSG_HEADER, ALTERATION_HEADER], ncols, newncols, defaultCancerType,
cancerTypeMap, annotatehotspots, default_reference_genome, include_descriptions)
if (query_type == QueryType.GENOMIC_CHANGE):
newncols = append_headers(outf, newncols, include_descriptions, True)
process_genomic_change(reader, outf, headers, ncols, newncols, defaultCancerType, cancerTypeMap,
annotatehotspots, default_reference_genome, include_descriptions)
outf.close()
def get_cell_content(row, index, return_empty_string=False):
if index >= 0 and row[index] != 'NULL' and row[index] != '':
return row[index]
elif return_empty_string:
return ''
else:
return None
def get_oncokb_annotation_column_headers(include_descriptions, genomic_change_annotation):
headers = [ANNOTATED_HEADER]
if genomic_change_annotation:
headers.extend(ONCOKB_ANNOTATION_HEADERS_GC)
headers.extend([GENE_IN_ONCOKB_HEADER,
VARIANT_IN_ONCOKB_HEADER,
"MUTATION_EFFECT",
"MUTATION_EFFECT_CITATIONS",
"ONCOGENIC"])
for level in sorted(levels):
headers.append(level)
headers.append("HIGHEST_LEVEL")
headers.append("HIGHEST_SENSITIVE_LEVEL")
headers.append("HIGHEST_RESISTANCE_LEVEL")
headers.append("TX_CITATIONS")
for dx_level in dxLevels:
headers.append(dx_level)
headers.append("HIGHEST_DX_LEVEL")
headers.append("DX_CITATIONS")
for px_level in pxLevels:
headers.append(px_level)
headers.append("HIGHEST_PX_LEVEL")
headers.append("PX_CITATIONS")
if include_descriptions:
headers.extend(DESCRIPTION_HEADERS)
return headers
def process_alteration(maffilereader, outf, maf_headers, alteration_column_names, ncols, nannotationcols,
defaultCancerType, cancerTypeMap,
annotatehotspots, default_reference_genome, include_descriptions):
ihugo = geIndexOfHeader(maf_headers, HUGO_HEADERS)
iconsequence = geIndexOfHeader(maf_headers, CONSEQUENCE_HEADERS)
ihgvs = geIndexOfHeader(maf_headers, alteration_column_names)
isample = geIndexOfHeader(maf_headers, SAMPLE_HEADERS)
istart = geIndexOfHeader(maf_headers, PROTEIN_START_HEADERS)
iend = geIndexOfHeader(maf_headers, PROTEIN_END_HEADERS)
iproteinpos = geIndexOfHeader(maf_headers, PROTEIN_POSITION_HEADERS)
icancertype = geIndexOfHeader(maf_headers, CANCER_TYPE_HEADERS)
ireferencegenome = geIndexOfHeader(maf_headers, REFERENCE_GENOME_HEADERS)
posp = re.compile('[0-9]+')
i = 0
queries = []
rows = []
for row in maffilereader:
i = i + 1
if i % POST_QUERIES_THRESHOLD == 0:
log.info(i)
row = padrow(row, ncols)
sample = row[isample]
if sampleidsfilter and sample not in sampleidsfilter:
continue
hugo = row[ihugo]
consequence = get_cell_content(row, iconsequence)
if consequence in mutationtypeconsequencemap:
consequence = '%2B'.join(mutationtypeconsequencemap[consequence])
hgvs = row[ihgvs]
if hgvs.startswith('p.'):
hgvs = hgvs[2:]
cancertype = get_tumor_type_from_row(row, i, defaultCancerType, icancertype, cancerTypeMap, sample)
reference_genome = get_reference_genome_from_row(get_cell_content(row, ireferencegenome),
default_reference_genome)
hgvs = conversion(hgvs)
start = get_cell_content(row, istart)
end = get_cell_content(row, iend)
if start is None and iproteinpos >= 0 and row[iproteinpos] != "" and row[iproteinpos] != "." and \
row[iproteinpos] != "-":
poss = row[iproteinpos].split('/')[0].split('-')
try:
if len(poss) > 0:
start = int(poss[0])
if len(poss) == 2:
end = int(poss[1])
except ValueError:
log.info("position wrong at line %s: %s" % (str(i), row[iproteinpos]))
if start is None and consequence == "missense_variant":
m = posp.search(hgvs)
if m:
start = m.group()
if start is not None and end is None:
end = start
query = ProteinChangeQuery(hugo, hgvs, cancertype, reference_genome, consequence, start, end)
queries.append(query)
rows.append(row)
if len(queries) == POST_QUERIES_THRESHOLD:
annotations = pull_protein_change_info(queries, include_descriptions, annotatehotspots)
append_annotation_to_file(outf, ncols + nannotationcols, rows, annotations)
queries = []
rows = []
if len(queries) > 0:
annotations = pull_protein_change_info(queries, include_descriptions, annotatehotspots)
append_annotation_to_file(outf, ncols + nannotationcols, rows, annotations)
# this method is from genome-nexus annotation-tools
# https://github.com/genome-nexus/annotation-tools/blob/53ff7f7fe673e961282f871ebc78d2ecc0831919/standardize_mutation_data.py
def get_var_allele(ref_allele, tumor_seq_allele1, tumor_seq_allele2):
# set the general tumor_seq_allele as the first non-ref allele encountered
# this will be used to resolve the variant classification and variant type
# if there are no tumor alleles that do not match the ref allele then use empty string
# in the event that this happens then there might be something wrong with the data itself
# if both alleles are different, use allele2. Stick with the logic of GenomeNexus
try:
tumor_seq_allele = ""
if ref_allele != tumor_seq_allele2:
tumor_seq_allele = tumor_seq_allele2
elif ref_allele != tumor_seq_allele1:
tumor_seq_allele = tumor_seq_allele1
except Exception:
tumor_seq_allele = ""
return tumor_seq_allele
def process_genomic_change(maffilereader, outf, maf_headers, ncols, nannotationcols, defaultCancerType, cancerTypeMap,
annotatehotspots, default_reference_genome, include_descriptions):
ichromosome = geIndexOfHeader(maf_headers, [GC_CHROMOSOME_HEADER])
istart = geIndexOfHeader(maf_headers, [GC_START_POSITION_HEADER])
iend = geIndexOfHeader(maf_headers, [GC_END_POSITION_HEADER])
irefallele = geIndexOfHeader(maf_headers, [GC_REF_ALLELE_HEADER])
ivarallele1 = geIndexOfHeader(maf_headers, [GC_VAR_ALLELE_1_HEADER])
ivarallele2 = geIndexOfHeader(maf_headers, [GC_VAR_ALLELE_2_HEADER])
isample = geIndexOfHeader(maf_headers, SAMPLE_HEADERS)
icancertype = geIndexOfHeader(maf_headers, CANCER_TYPE_HEADERS)
ireferencegenome = geIndexOfHeader(maf_headers, REFERENCE_GENOME_HEADERS)
i = 0
queries = []
rows = []
for row in maffilereader:
i = i + 1
if i % POST_QUERIES_THRESHOLD_GC_HGVSG == 0:
log.info(i)
row = padrow(row, ncols)
sample = row[isample]
if sampleidsfilter and sample not in sampleidsfilter:
continue
cancertype = get_tumor_type_from_row(row, i, defaultCancerType, icancertype, cancerTypeMap, sample)
reference_genome = get_reference_genome_from_row(get_cell_content(row, ireferencegenome),
default_reference_genome)
chromosome = get_cell_content(row, ichromosome, True)
start = get_cell_content(row, istart, True)
end = get_cell_content(row, iend, True)
ref_allele = get_cell_content(row, irefallele, True)
var_allele_1 = get_cell_content(row, ivarallele1, True)
var_allele_2 = get_cell_content(row, ivarallele2, True)
var_allele = get_var_allele(ref_allele, var_allele_1, var_allele_2)
query = GenomicChangeQuery(chromosome, start, end, ref_allele, var_allele, cancertype, reference_genome)
queries.append(query)
rows.append(row)
if len(queries) == POST_QUERIES_THRESHOLD_GC_HGVSG:
annotations = pull_genomic_change_info(queries, include_descriptions, annotatehotspots)
append_annotation_to_file(outf, ncols + nannotationcols, rows, annotations)
queries = []
rows = []
if len(queries) > 0:
annotations = pull_genomic_change_info(queries, include_descriptions, annotatehotspots)
append_annotation_to_file(outf, ncols + nannotationcols, rows, annotations)
def process_hvsg(maffilereader, outf, maf_headers, alteration_column_names, ncols, nannotationcols, defaultCancerType,
cancerTypeMap, annotatehotspots, default_reference_genome, include_descriptions):
ihgvsg = geIndexOfHeader(maf_headers, alteration_column_names)
isample = geIndexOfHeader(maf_headers, SAMPLE_HEADERS)
icancertype = geIndexOfHeader(maf_headers, CANCER_TYPE_HEADERS)
ireferencegenome = geIndexOfHeader(maf_headers, REFERENCE_GENOME_HEADERS)
i = 0
queries = []
rows = []
for row in maffilereader:
i = i + 1
if i % POST_QUERIES_THRESHOLD_GC_HGVSG == 0:
log.info(i)
row = padrow(row, ncols)
sample = row[isample]
if sampleidsfilter and sample not in sampleidsfilter:
continue
hgvsg = get_cell_content(row, ihgvsg)
cancertype = get_tumor_type_from_row(row, i, defaultCancerType, icancertype, cancerTypeMap, sample)
reference_genome = get_reference_genome_from_row(get_cell_content(row, ireferencegenome),
default_reference_genome)
if hgvsg is None:
if annotatehotspots:
default_cols = [['', '', 'False']]
else:
default_cols = [['False']]
append_annotation_to_file(outf, ncols + nannotationcols, [row],
default_cols)
else:
query = HGVSgQuery(hgvsg, cancertype, reference_genome)
queries.append(query)
rows.append(row)
if len(queries) == POST_QUERIES_THRESHOLD_GC_HGVSG:
annotations = pull_hgvsg_info(queries, include_descriptions, annotatehotspots)
append_annotation_to_file(outf, ncols + nannotationcols, rows, annotations)
queries = []
rows = []
if len(queries) > 0:
annotations = pull_hgvsg_info(queries, include_descriptions, annotatehotspots)
append_annotation_to_file(outf, ncols + nannotationcols, rows, annotations)
def getgenesfromfusion(fusion, nameregex=None):
GENES_REGEX = r"([A-Za-z\d]+-[A-Za-z\d]+)" if nameregex is None else nameregex
searchresult = re.search(GENES_REGEX, fusion, flags=re.IGNORECASE)
geneA = None
geneB = None
if searchresult:
parts = searchresult.group(1).split("-")
geneA = parts[0]
geneB = geneA
if len(parts) > 1 and parts[1] != "intragenic":
geneB = parts[1]
else:
geneA = geneB = fusion
return geneA, geneB
def process_fusion(svdata, outfile, previousoutfile, defaultCancerType, cancerTypeMap, nameregex, include_descriptions):
if os.path.isfile(previousoutfile):
cacheannotated(previousoutfile, defaultCancerType, cancerTypeMap)
outf = open(outfile, 'w+')
with open(svdata, DEFAULT_READ_FILE_MODE) as infile:
reader = csv.reader(infile, delimiter='\t')
headers = readheaders(reader)
ncols = headers["length"]
if ncols == 0:
return
outf.write(headers['^-$'])
oncokb_annotation_headers = get_oncokb_annotation_column_headers(include_descriptions, False)
outf.write("\t")
outf.write("\t".join(oncokb_annotation_headers))
outf.write("\n")
newcols = ncols + len(oncokb_annotation_headers)
igeneA = geIndexOfHeader(headers, SV_GENEA_HEADER)
igeneB = geIndexOfHeader(headers, SV_GENEB_HEADER)
ifusion = geIndexOfHeader(headers, FUSION_HEADERS)
isample = geIndexOfHeader(headers, SAMPLE_HEADERS)
icancertype = geIndexOfHeader(headers, CANCER_TYPE_HEADERS)
i = 0
queries = []
rows = []
for row in reader:
i = i + 1
if i % POST_QUERIES_THRESHOLD == 0:
log.info(i)
row = padrow(row, ncols)
sample = row[isample]
if sampleidsfilter and sample not in sampleidsfilter:
continue
geneA = None
geneB = None
if igeneA >= 0:
geneA = row[igeneA]
if igeneB >= 0:
geneB = row[igeneB]
if igeneA < 0 and igeneB < 0 and ifusion >= 0:
fusion = row[ifusion]
geneA, geneB = getgenesfromfusion(fusion, nameregex)
cancertype = get_tumor_type_from_row(row, i, defaultCancerType, icancertype, cancerTypeMap, sample)
queries.append(StructuralVariantQuery(geneA, geneB, 'FUSION', cancertype))
rows.append(row)
if len(queries) == POST_QUERIES_THRESHOLD:
annotations = pull_structural_variant_info(queries, include_descriptions)
append_annotation_to_file(outf, newcols, rows, annotations)
queries = []
rows = []
if len(queries) > 0:
annotations = pull_structural_variant_info(queries, include_descriptions)
append_annotation_to_file(outf, newcols, rows, annotations)
outf.close()
def process_sv(svdata, outfile, previousoutfile, defaultCancerType, cancerTypeMap, include_descriptions):
if os.path.isfile(previousoutfile):
cacheannotated(previousoutfile, defaultCancerType, cancerTypeMap)
outf = open(outfile, 'w+')
with open(svdata, DEFAULT_READ_FILE_MODE) as infile:
reader = csv.reader(infile, delimiter='\t')
headers = readheaders(reader)
ncols = headers["length"]
if ncols == 0:
return
outf.write(headers['^-$'])
oncokb_annotation_headers = get_oncokb_annotation_column_headers(include_descriptions, False)
outf.write("\t")
outf.write("\t".join(oncokb_annotation_headers))
outf.write("\n")
newcols = ncols + len(oncokb_annotation_headers)
igeneA = geIndexOfHeader(headers, SV_GENEA_HEADER)
igeneB = geIndexOfHeader(headers, SV_GENEB_HEADER)
isvtype = geIndexOfHeader(headers, SV_TYPE_HEADER)
isample = geIndexOfHeader(headers, SAMPLE_HEADERS)
icancertype = geIndexOfHeader(headers, CANCER_TYPE_HEADERS)
i = 0
queries = []
rows = []
for row in reader:
i = i + 1
if i % POST_QUERIES_THRESHOLD == 0:
log.info(i)
row = padrow(row, ncols)
sample = row[isample]
if sampleidsfilter and sample not in sampleidsfilter:
continue
if igeneA < 0 or igeneB < 0:
log.warning("Please specify two genes")
continue
svtype = None
if isvtype >= 0:
svtype = row[isvtype].upper()
if svtype not in SV_TYPES:
svtype = None
if svtype is None:
svtype = UNKNOWN
cancertype = get_tumor_type_from_row(row, i, defaultCancerType, icancertype, cancerTypeMap, sample)
sv_query = StructuralVariantQuery(row[igeneA], row[igeneB], svtype, cancertype)
queries.append(sv_query)
rows.append(row)
if len(queries) == POST_QUERIES_THRESHOLD:
annotations = pull_structural_variant_info(queries, include_descriptions)
append_annotation_to_file(outf, newcols, rows, annotations)
queries = []
rows = []
if len(queries) > 0:
annotations = pull_structural_variant_info(queries, include_descriptions)
append_annotation_to_file(outf, newcols, rows, annotations)
outf.close()
def get_cna(cell_value, annotate_gain_loss=False):
cna = None
if cell_value is not None and cell_value != '':
if cell_value in GISTIC_CNA_MAP:
cna = GISTIC_CNA_MAP[cell_value]
else:
for default_cna in CNAS:
if cell_value.upper() == default_cna.upper():
cna = default_cna
if not annotate_gain_loss and cna is not None and cna.upper() in [CNA_GAIN_TXT.upper(), CNA_LOSS_TXT.upper()]:
cna = None
return cna
def process_gistic_data(outf, gistic_data_file, defaultCancerType, cancerTypeMap, annotate_gain_loss,
include_descriptions):
with open(gistic_data_file, DEFAULT_READ_FILE_MODE) as infile:
reader = csv.reader(infile, delimiter='\t')
headers = readheaders(reader)
samples = []
rawsamples = []
if headers["length"] != 0:
startofsamples = getfirstcolumnofsampleingisticdata(headers['^-$'].split('\t'))
rawsamples = headers['^-$'].split('\t')[startofsamples:]
for rs in rawsamples:
samples.append(rs)
if defaultCancerType == '' and not set(cancerTypeMap.keys()).issuperset(set(samples)):
log.info(
"Cancer type for all samples should be defined for a more accurate result\nsamples in cna file: %s\n" % (
samples))
i = 0
rows = []
queries = []