Associate Professor of Medicine
Kristine and Bob Higgins MGH Research Scholar
Ragon Institute of MGH, MIT and Harvard
"Programming Killer Antibodies"
Sponsored by the Penn Center for AIDS Research (CFAR).
Seminar title: Antibiotics and early life development
"Bayesian Modeling of Epigenetic Variation in Multiple Human Cell Types"
Yu Zhang, PhD Associate Professor of Statistics Department of Statistics Pennsylvania State University
Abstract: With massive amount of sequencing data generated for many chromatin modifications in a variety of cell/tissue types, the chief challenges are to build effective and quantitative models explaining how the dynamics in multiple epigenomes lead to differential gene expression and diverse phenotypes. Current state-of-the-art approaches for characterizing epigenetic landscapes are via genome segmentation, yet existing segmentation tools ignore the critical information of position specificity of epigenetic events and often treat all epigenomes equally without considering cell type-specific regulation in local regions. We developed a unified Bayesian framework for jointly annotating multiple epigenomes and detecting differential regulation among multiple tissues and cell types over regions of varying sizes. The method, called IDEAS (integrative and discriminative epigenome annotation system), achieves superior power and accuracy over existing methods by modeling both position and cell type specific regulatory activities. Using 84 genome-wide epigenetic data sets in 6 cell types from ENCODE, we identified epigenetic variation that are strongly associated with differential gene expression. The detected regions are significantly enriched in genetic variants associated with complex phenotypes that are highly relevant to the corresponding cell types. They yielded much stronger enrichment scores than that achievable by existing approaches. Our analysis of cell type specificity could be of great importance in elucidating the interplay between genetic variants, gene regulation and diseases.
This is a joint work with Feng Yue and Ross Hardison.