FORGEdb: a tool for identifying candidate functional variants and uncovering target genes and mechanisms for complex diseases

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作者
Charles E. Breeze
Eric Haugen
María Gutierrez-Arcelus
Xiaozheng Yao
Andrew Teschendorff
Stephan Beck
Ian Dunham
John Stamatoyannopoulos
Nora Franceschini
Mitchell J. Machiela
Sonja I. Berndt
机构
[1] National Cancer Institute,Division of Cancer Epidemiology and Genetics
[2] National Institutes of Health,Division of Immunology, Department of Pediatrics
[3] Altius Institute for Biomedical Sciences,CAS Key Lab of Computational Biology, Shanghai Institute for Biological Sciences
[4] UCL Cancer Institute,European Molecular Biology Laboratory
[5] University College London,Department of Epidemiology
[6] Boston Children’s Hospital,undefined
[7] Harvard Medical School,undefined
[8] Broad Institute of MIT and Harvard,undefined
[9] CAS-MPG Partner Institute for Computational Biology,undefined
[10] Chinese Academy of Sciences,undefined
[11] European Bioinformatics Institute (EMBL-EBI),undefined
[12] University of North Carolina,undefined
来源
关键词
Gene regulation; Functional annotation; Variant scoring; Regulatory elements; Genome-wide association study (GWAS); Expression quantitative trait locus (eQTL); Massively parallel reporter assay (MPRA); Activity-by-contact (ABC); DNase-seq; Transcription factor (TF); CRISPR (clustered regularly interspaced short palindromic repeats); Single guide RNA (sgRNA);
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摘要
The majority of disease-associated variants identified through genome-wide association studies are located outside of protein-coding regions. Prioritizing candidate regulatory variants and gene targets to identify potential biological mechanisms for further functional experiments can be challenging. To address this challenge, we developed FORGEdb (https://forgedb.cancer.gov/; https://forge2.altiusinstitute.org/files/forgedb.html; and https://doi.org/10.5281/zenodo.10067458), a standalone and web-based tool that integrates multiple datasets, delivering information on associated regulatory elements, transcription factor binding sites, and target genes for over 37 million variants. FORGEdb scores provide researchers with a quantitative assessment of the relative importance of each variant for targeted functional experiments.
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