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Activity Number: 242
Type: Contributed
Date/Time: Monday, August 1, 2016 : 2:00 PM to 3:50 PM
Sponsor: Biometrics Section
Abstract #320222 View Presentation
Title: Mapping Three-Dimensional Organization in Repetitive Regions of the Genomes
Author(s): Ye Zheng* and Sunduz Keles and Ferhat Ay
Companies: University of Wisconsin - Madison and University of Wisconsin - Madison and La Jolla Institute for Allergy and Immunology
Keywords: Hi-C ; Repetitive Regions ; Generative Model ; Three-dimensional Chromosomal Structure

A series of recently developed chromatin conformation capture-based assays (3C, 4C, 5C and Hi-C) enabled the study of three-dimensional chromosomal structures and elucidated long-range genomic interactions among loci. However, current Hi-C analysis pipelines of these data discard reads aligning to multiple locations (multi-reads) and, hence, underestimate intra-chromosomal and inter-chromosomal interactions involving repetitive regions. We study this problem in depth and train a generative model to probabilistically allocate multi-reads contacts. This highly versatile model is extendable to a Bayesian hierarchical model by utilizing auxiliary protein-DNA interaction data as prior to improve the allocation accuracy. Our results suggest that effective utilization of multi-reads, on average, increases sequencing depth by 21% and, hence, identifies up to 10% more significant long-range interactions even under a conservative setting. Most of the new contacts are uniquely detected when multi-reads are employed and they originate from heterochromatin regions. Further analysis of these new interactions highlight the importance of long-range interactions originating from repetitive regions.

Authors who are presenting talks have a * after their name.

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