MSTD for detecting topological domains from 3D genomic maps

Abstract

In this chapter, we introduce a generic and efficient method to identify multiscale topological domains (MSTD), including cis- and trans-interacting regions, from a variety of 3D genomic datasets. We first applied MSTD to detect promoter-anchored interaction domains (PADs) from promoter capture Hi-C datasets across 17 primary blood cell types. The boundaries of PADs are significantly enriched with one or the combination of multiple epigenetic factors. Moreover, PADs between functionally similar cell types are significantly conserved in terms of domain regions and expression states. Cell type-specific PADs involve in distinct cell type-specific activities and regulatory events by dynamic interactions within them. We also employed MSTD to define multiscale domains from typical symmetric Hi-C datasets and illustrated its distinct superiority to the state-of-the-art methods in terms of accuracy, flexibility and efficiency.