Joint inference and alignment of genome structures enables characterization of compartment-independent 3D relocalization across cell types

ABSTRACT Cell-type-specific chromosome conformation is correlated with differential gene regulation. We developed MultiMDS to jointly infer and align 3D chromosomal structures from Hi-C datasets, thereby enabling a new way to comprehensively quantify relocalization of genomic loci between cell types. We demonstrate this approach by comparing Hi-C data across a variety of cell types. We consistently find relocalization of loci with minimal difference in A/B compartment score. Some such compartment-independent relocalizations involve loci that display enhancer-associated histone marks in one cell type and polycomb-associated histone marks in the other. MultiMDS thus detects types of relocalizations that are missed by other approaches. Availabilityhttps://github.com/seqcode/multimds