Seminar Series: Computational and Statistical Methods for the Genetic Analysis of the Regulatory Genome.

Learning the gene regulatory grammar encoded in the human genome is a fundamental step in understanding the role of non-coding genetic variation in human phenotypes. My talk will focus on the challenges and methods for analyzing large genomic datasets to study and integrate information on transcription regulation, chromatin state/accessibility, gene-environment interactions, and genetics of complex traits. The first part of the talk will cover computational methods for identifying gene regulatory elements and predicting the effect of genetic variants on gene regulation. I will then cover statistical genetics methods that can integrate this annotation for quantitative trait loci (QTL) analysis of both molecular and organismal phenotypes. I will present allele specific methods we developed to validate the computational predictions and to identify changes of the genetic effects on gene expression across different environmental conditions. Using these methods we demonstrated that the majority of genes that show condition specific allelic effects are also enriched for associations identified by genome-wide association studies (GWAS). Finally, I will present ongoing work on identifying genomic regions and regulatory sequences that determine gene expression response to specific environmental perturbations.