Olga is a post doc in the labs of Stephen Montgomery and Tom Quertermous.
Functional genomics of vascular smooth muscle cell differentiation
Coronary heart disease (CHD) and other complex human pathologies are products of genetic and environmental factors whose interactions are poorly understood. Genome-wide association studies (GWAS) demonstrate that most disease-associated genetic variants modulate the expression profile of a given gene, not the structure of its protein product. Thus, precise identification of regulatory SNPs and the environment-specific mechanisms of their function is critical for developing novel therapeutics in the post-genomic era. To this end, we have developed a novel computational method to detect gene-environment (GxE) interactions from RNA-Seq data by mapping differential allele-specific expression (dASE) in response to an environmental stimulus. We applied this method to detect dASE in vascular smooth muscle cells (VSMCs) exposed to a healthy or disease-like environment and discovered 72 genes (5% FDR) exhibiting dASE as a function of serum stimulation. Only 28 of these 72 genes were shown to exhibit differential expression (dE), illustrating the power of rASE to reveal environment-responsive transcriptional regulation not captured by conventional differential expression analysis. Further, we found enrichment of genes associated with coronary heart disease by GWAS among dASE genes but not dE genes, and this result further suggests that dASE mapping can reveal novel mechanistic insights about the identify and function of causal variants implicated in disease risk. Our pipeline can be applied to any paired case-control RNA-Seq data set to discover the presence of environment-sensitive regulatory variants and offers a novel and powerful avenue to study GxE interactions in complex human disease.
Wednesday Feb 19, 2014
1:00 PM Lunch
1:15 PM Seminar
Location: Clark Center S360
Host: Stephen Montgomery