MorbidGenes panel: a monthly updated list of diagnostically relevant genes derived from diverse sources

Table of Contents

• Overview
• Installation and Setup
• Usage
• Repository Structure
• Authors
• Contributing
• License
• Acknowledgments

Overview

Identifying clinically relevant genetic variants is crucial for a fast and reliable genetic diagnosis. With exome sequencing now standard, diagnostic labs are in need of a, in principle, to-the-day-accurate list of genes associated with rare diseases. Manual curation efforts are slow and often disease specific, while efforts relying on single sources are too inaccurate and may result in false-positive genes.

We established the MorbidGenes panel based on a list of publicly available databases: OMIM, PanelApp, SysNDD, ClinVar, HGMD and GenCC. A simple logic allows inclusion of genes with sufficient evidence based on a voting algorithm. By providing an API endpoint, users can directly access the list and metadata for all relevant information on their genes of interest.

The panel currently includes 4,677 genes (v.2022-02.1, as of February 2022) with minimally sufficient evidence on disease causality to classify them as diagnostically relevant. Reproducible filtering and versioning allow the integration into diagnostic pipelines. In-house implementation successfully removed false positive genes and reduced time requirements in routine exome diagnostics. The panel is updated monthly, and we will integrate novel sources on a regular basis. The panel is freely available at https://morbidgenes.org/.

The MorbidGenes panel is a comprehensive and open overview of clinically relevant genes based on a growing list of sources. It supports genetic diagnostics labs by providing diagnostically relevant genes in a QM conform format on a monthly basis with more frequent updates planned. Once genomes are standard, diagnostically relevant non-coding regions will also be included.

Installation and Setup

Follow the instructions in deployment.sh to deploy the project.

Usage

• Frontend: Navigate to the app directory.
• Backend API: Navigate to the api directory.
• Database: Navigate to the db directory.

Repository Structure

morbidgenes/
    .gitignore
    LICENSE
    README.md
    deployment.sh
    docker-compose.yml
    api/
        .gitignore
        Dockerfile
        README.md
        morbidgenes-db_plumber.R
        start_api.R
        data/
        functions/
    app/
        .env
        .env.production
        .eslintrc.json
        .gitignore
        Dockerfile
        README.md
        babel.config.js
        package-lock.json
        package.json
        postcss.config.js
        vue.config.js
        docker/
        public/
        src/
            App.vue
            main.js
            assets/
            components/
            plugins/
            router/
            views/
    db/
        README.md
        R/
            01_morbidgenes_table_hgnc_non_alt_loci_set.R
            02_morbidgenes_db_create_tables-from-csv.R
            03_morbidgenes_db_create_table_user.R
            04_morbidgenes_db_create-database-tables-in-mysql.R
            05_morbidgenes_db_set-table-connections.R
            README.md
            config_dummy.yml
            data/
            functions/
            results/

Authors

Contributors names and contact info

• Bernt Popp, ORCID ID: 0000-0002-3679-1081, @berntpopp
• Rami Abou Jamra, ORCID ID: 0000-0002-1542-1399, @RamiJamra
• Konrad Platzer, ORCID ID: 0000-0001-6127-6308, @platzer_k
• Joachim Bachmann, ORCID ID: 0000-0003-0552-6856
• Robin-Tobias Jauss, ORCID ID: 0000-0002-8285-9155, @RTJauss

Contributing

Feel free to open issues or submit pull requests.

Version History

• 0.1.0
  • Initial GitHub Release

License

This project is licensed under the terms of the BSD 3-Clause.

Acknowledgments