Final Report Summary - CHROMATIN DOMAINS (Differentially Accessible Chromatin Domains and Their Transcriptional Regulatory Role in Health and Disease) We are a computational research group, led by Dr. Tommy Kaplan, in the School of Computer Science and Engineering, the Hebrew University. Our group, established in Fall 2012, is composed of one postdoc fellow, one MD/PhD student, and six MSc students, with many active collaborations with experimental groups in Israel and abroad. We study the chromatin dynamics and the organization of the genome in 3D. For this, we are developing computational methods for integrating vast amounts of publicly available heterogeneous data and identify the organization of the genome into “Chromatin Domains” - the atomic units of genome packaging. For this, we rely on genome-wide high-throughput data. Currently, we mostly use Hi-C data from various biological conditions and tissues. Additional data we use includes DNA accessibility (DNaseI and ATAC-seq), histone modifications, including H3K27ac, H3K27me3, H3K4me1, etc.We developed computational methods that are based on Hidden Markov Models and other Dynamics Programming algorithms that integrate these genomic tracks (either in a discretize or a continuous form) and identify “natural” boundary regions and define minimal autonomous Chromatin Domains. We then re-use the Histone Modification data to identify the functional role of each.These data will be integrated with condition specific high-throughput DNA-DNA interaction data (Hi-C and ChIA-PET) to identify specific interactions between, for example, regulatory regions and their target genes.
