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Deciphering Hierarchical Organization Of Topologically Associated Domains Through Change-Point Testing., Haipeng Xing, Yingru Wu, Michael Q Zhang, Yong Chen
Deciphering Hierarchical Organization Of Topologically Associated Domains Through Change-Point Testing., Haipeng Xing, Yingru Wu, Michael Q Zhang, Yong Chen
Faculty Scholarship for the College of Science & Mathematics
BACKGROUND: The nucleus of eukaryotic cells spatially packages chromosomes into a hierarchical and distinct segregation that plays critical roles in maintaining transcription regulation. High-throughput methods of chromosome conformation capture, such as Hi-C, have revealed topologically associating domains (TADs) that are defined by biased chromatin interactions within them.
RESULTS: We introduce a novel method, HiCKey, to decipher hierarchical TAD structures in Hi-C data and compare them across samples. We first derive a generalized likelihood-ratio (GLR) test for detecting change-points in an interaction matrix that follows a negative binomial distribution or general mixture distribution. We then employ several optimal search strategies to …