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

Genome Biol. 2024 Jan 2;25(1):3. doi: 10.1186/s13059-023-03126-1.

Abstract

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.

Keywords: Activity-by-contact (ABC); CRISPR (clustered regularly interspaced short palindromic repeats); DNase-seq; Expression quantitative trait locus (eQTL); Functional annotation; Gene regulation; Genome-wide association study (GWAS); Massively parallel reporter assay (MPRA); Regulatory elements; Single guide RNA (sgRNA); Transcription factor (TF); Variant scoring.

MeSH terms

  • Genome-Wide Association Study*
  • Polymorphism, Single Nucleotide
  • Protein Binding
  • Regulatory Sequences, Nucleic Acid*