Publications by authors named "Tejal A Patwardhan"
Genome-wide association studies (GWASs) are a valuable tool for understanding the biology of complex human traits and diseases, but associated variants rarely point directly to causal genes. In the present study, we introduce a new method, polygenic priority score (PoPS), that learns trait-relevant gene features, such as cell-type-specific expression, to prioritize genes at GWAS loci. Using a large evaluation set of genes with fine-mapped coding variants, we show that PoPS and the closest gene individually outperform other gene prioritization methods, but observe the best overall performance by combining PoPS with orthogonal methods.
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- Genome-wide association studies (GWAS) have found many noncoding regions related to diseases, but translating these findings into functional insights is challenging due to insufficient maps of enhancers and target genes.
- The activity-by-contact (ABC) model was developed to predict enhancer-gene interactions and applied across 131 human cell types, linking over 5,000 GWAS signals to nearly 2,250 unique genes with implications for various diseases.
- Specifically for inflammatory bowel disease (IBD), ABC model identified risk variants in enhancers that regulate gene expression, offering a new understanding of disease mechanisms and providing a blueprint for future connections between genetic variants and their functions.
Enhancer elements in the human genome control how genes are expressed in specific cell types and harbor thousands of genetic variants that influence risk for common diseases. Yet, we still do not know how enhancers regulate specific genes, and we lack general rules to predict enhancer-gene connections across cell types. We developed an experimental approach, CRISPRi-FlowFISH, to perturb enhancers in the genome, and we applied it to test >3,500 potential enhancer-gene connections for 30 genes.
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