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Dr. Ferhat Ay
Associate Professor
Centers for Autoimmunity and Cancer Immunotherapy
La Jolla Institute for Immunology

Computational Methods for Studying the 3D Organization of the Human Genome

The field of regulatory genomics has recently witnessed significantly increased interest in the three-dimensional structure of DNA in the nucleus, catalyzed by the development of chromosome conformation capture techniques (e.g., Hi-C, HiChIP) that profile genomic proximities on a genome-wide scale. Systematic analysis of these proximities is particularly important to identify targets of disease-associated genetic variants, more than 90% of which reside in non-coding regions with unknown gene targets. Our lab works on developing computational methods to understand the role of human genetic variation in gene regulation through various epigenetic mechanisms, and in particular, through chromatin structure. I will talk about our work in developing computational methods (FitHiC, FitHiChIP, Mustache) for the analysis of Hi-C and HiChIP data in order to determine functional loops between regulatory elements in our DNA. I will then present the results of our recently published work (Chandra et al. Nature Genetics 2020), in which we profile such loops in primary human immune cell types and revisit the functional roles of GWAS SNPs in immune-mediated diseases. Our results highlight the problems with "the nearest gene" approach for mapping GWAS hits or enhancers to target genes and the importance of combining high resolution, high throughput experiments with novel computational techniques to achieve an accurate mapping of target genes.