Performing experiments to understand gene regulation and do not want to miss any extra points? Well, FORGEdb may be the method for you! Building on previous research, this new method can help scientists unravel the mysteries behind complex diseases by identifying candidate functional variants and uncovering target genes and mechanisms. Developed by a team led by Charles E. Breeze, this method promises to accelerate our understanding of genetic variants and their influence on diseases.
Disease-associated variants identified through genome-wide association studies (GWAS) generally locate to outside protein-coding regions, posing a challenge when trying to pinpoint functional significance. FORGEdb addresses this challenge by integrating multiple datasets, including regulatory elements, transcription factor binding sites, and target genes for over 37 million variants. This comprehensive approach provides researchers with a quantitative assessment of the relative importance of each variant for targeted functional experiments.
The tool utilizes a novel scoring system that combines various lines of evidence for regulatory function into a single score. By incorporating data from diverse experimental approaches, including chromatin accessibility, histone modifications, 3D genomic interactions, differential gene expression, and transcription factor binding, this method offers a comprehensive view of the functional impact of genetic variants.
The ability to prioritize variants using multidimensional data represents a strength of FORGEdb. The authors tested and validated their method for various human traits/diseases; analysis of summary statistics from 30 GWAS indicated that variants with higher FORGEdb scores more likely associate with functional impact on a disease/trait. Furthermore, the scores displayed a significant overrepresentation of expression-modulating variants identified from massively parallel reporter assays, suggesting that variants with higher FORGEdb scores are more likely to be functional. These findings underscore the utility of FORGEdb in prioritizing variants for experimental validation and functional studies.
Overall, FORGEdb represents a significant advancement in the field and holds great promise for accelerating our understanding of the underlying mechanisms of complex diseases. The user-friendly interface and comprehensive features will likely make FORGEdb an indispensable tool for researchers seeking to decode the genetic basis of human diseases. FORGEdb is freely accessible via web browser, and researchers interested in exploring the tool further can access the source code and additional files on GitHub.
Let FORGEdb be the touchdown pass you need! Read more at Genome Biology, January 2024.