Computer Science and Engineering Colloquium Talk / Winter 2016
Melissa Gymrek, PhD
Massachusetts General Hospital and the Broad Institute
Friday, February 26, 2016
12 – 1 p.m.
Computer Science and Engineering Building EBU-3B, Room CSE 1202
Title: Dissecting the Contribution of Complex Genetic Variation to Human Traits
Recent studies have made substantial progress in identifying genetic variants associated with disease and molecular phenotypes in humans. However, these studies have primarily focused on single nucleotide polymorphisms (SNPs), ignoring more complex variants that have been shown to play important functional roles. Here, I focus on short tandem repeats (STRs), one of the most polymorphic and abundant classes of genetic variation. I will first present lobSTR, a novel algorithm for genotyping STRs from whole-genome sequencing datasets. Next, I will describe insights into population-wide trends of STR variation revealed by applying lobSTR to thousands of sequencing datasets to generate the largest and highest-quality STR catalog to date. I will then show how we used this catalog to conduct a genome-wide analysis of the contribution of STRs to gene expression in humans. This survey revealed that STRs explain 10-15% of the heritability of expression mediated by all common cis variants and potentially play an important role in clinically relevant conditions. Finally, I will discuss preliminary analyses incorporating functional genomics data with high-quality complex variant genotypes to predict and validate the function of non-coding variants driving common human diseases. Altogether, these results highlight the putative phenotypic contribution of complex variants and the opportunity for a wealth of genetic discoveries to be gained by expanding analyses to less-understood regions of the genome.
I am currently a post-doctoral fellow at Massachusetts General Hospital and the Broad Institute. I recently received my PhD in Bioinformatics and Integrative Genomics from the Harvard/MIT Division of Health Sciences and Technology under the supervision of Yaniv Erlich and Mark Daly. Prior to my PhD, I received my B.S. in Computer Science and Mathematics at MIT.
My major research interest is to understand complex genetic variants that underlie phenotypic changes, ultimately leading to human disease. My recent work focuses on repetitive DNA variants known as short tandem repeats (STRs) as a model for complex variation. I develop computational methods for analyzing and visualizing complex variation from large-scale sequencing data. These tools allow us for the first time to answer many questions regarding STRs and other variant types, including their contribution to complex human phenotypes. In future work, I aim to build on my experience dissecting challenging regions of the genome to develop and test predictive models of the regulatory effects of complex sequence variation.
Vineet Bafna, PhD
Professor of Computer Science and Engineering
Jacobs School of Engineering
UC San Diego