This is a past event
Interdisciplinary seminar by Dr Andrii Iakovliev (University of Edinburgh).
Title: Identifying putative drug targets via aggregated genetic effects on distant gene function.
Abstract: Genetic studies have historically fallen short of their promise for drug target discovery due to an oversimplified understanding of disease mechanisms. Existing approaches typically assume that disease-associated genetic variants primarily affect nearby genes, overlooking the complex regulatory networks where variants exert subtle, long-range effects on distant genes, also termed trans-effects.
We developed genome-wide aggregated trans-effects (GATE) analysis, a novel machine learning approach to identify "core genes" which are pivotal in disease pathogenesis and encode promising therapeutic targets.
GATE systematically detects and aggregates trans-regulatory effects of genetic variants across the genome, using large-scale studies of gene expression and protein levels in blood samples. The genes where these aggregated effects differ significantly between individuals with and without disease reveal the convergence points of disease mechanisms.
We applied GATE to type 1 diabetes, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus and identified core genes and pathways that conventional genetic approaches had missed. These discoveries align with findings from laboratory-based immunology research and importantly, several identified targets are already being pursued in drug development programs.
We thus demonstrated that GATE analysis successfully identifies therapeutically relevant core genes by capturing the distributed, trans-regulatory architecture underlying complex diseases.
- Speaker
- Dr Andrii Iakovliev
- Venue
- Meston 311