Prediction and simulation in the 3D genome

  • Speaker: Zhi-Hua Zhang

  •              Beijing Institute of genome research, Chinese Academy of Sciences

  • Time: 10:00 a.m., Thursday, Jan.4th, 2017

  • Venue: Conference Room 104, Science Building, Tsinghua University

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  •  High throughput chromosome conformation capture technologies such as Hi-C, have made it possible to survey the 3D genome structure. However, due to inherent limitations of the technologies, it is remains a major challenge to obtain 3D profiles at kilobase resolution at low cost. Here, we present a simulation method to survey the dynamic of 3D structure of genome, and CISD, a computational method to precisely identify chromatin interaction sites from MNase-seq data. Based on CISD, we also developed a method (CISD_loop) to predict chromatin interactions with low resolution Hi-C data. The methods are based on a hypothesis that chromatin-chromatin interactions (CCI) result in a characteristic nucleosomes arrangement pattern flanking the interaction loci. We show that CISD predicted loci overlap closely with known CCI sites, e.g, ChIA-PET loop anchors and Hi-C looping hubs, at kilobase resolution. We further show that ChIA-PET loops were enriched in CISD_loop predicted CCIs. Moreover, by 3C experiments at 5kb resolution, we experimentally validated two CISD_loop predictions, which were not reported in current ChIA-PET data. The predictive power of CISD/CISD_loop supports the hypothesis that CCIs induce local nucleosome patterns that may serve as probes for the 3D dynamics of the genome. Finally, we showed that only modest amounts of MNase-seq and Hi-C data are sufficient to achieve ultrahigh resolution map of CCIs. Thus, our method will facilitate precise and systematic investigations of the interactions between distal regulatory elements on a larger scale than hitherto have been possible.