Abstract:
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The advent and rapid development of chromosome conformation capture (3C)-based technologies, in particular its genome-wide extension Hi-C technology, enable a genome-wide view of chromosome spatial organization. The constantly accumulating Hi-C datasets provide rich information for studying three-dimensional (3D) genome organization across multiple cell differentiation stages. However, the statistical models and computational tools for detecting dynamic long-range chromatin interactions (i.e., peaks) are still lacking. Limited sequencing depth within each Hi-C dataset, as well as heterogeneity among different Hi-C datasets, pose great challenges for downstream data analysis and data interpretation. To fill in these gaps, we here develop a Bayesian hierarchical hidden Markov random field (HHMRF)-based model to detect dynamic long-range chromatin interactions from Hi-C data collected from different cell types. Our method can effectively borrow information from multiple Hi-C datasets, therefore achieve higher robustness and enhanced statistical power. We applied HHMRF to analyze Hi-C datasets on human embryonic stem cells (H1 ESC) and four H1 derived cells, and identified a large numb
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