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Contact domains are closely linked to gene regulation and lineage commitment, while current understanding of contact domains and their boundaries is still limited. Here, we present a novel method HiCDB, which is constructively based on local relative insulation metric and multi-scale aggregation approach to detect contact domain boundaries (CDBs) on Hi-C maps. Compared with other 'state-of-art' methods, HiCDB shows improved sensitivity and specificity in determining CDBs at various Hi-C resolutions. The superiority of HiCDB enabled us to study the epigenetic features of detected CDBs and showed enrichment of architectural proteins and cell-type-specific transcription factor binding sites at CDBs. The further comparison of GM12878 and IMR90 Hi-C datasets suggested that cell-type-specific CDBs are marked by active regulatory signals and correlate with activation of nearby cell identity genes.

HiCDB: a sensitive and robust method for detecting contact domain boundaries