Mammalian genomes are folded in a hierarchy of compartments, topologically associating domains (TADs), subTADs and looping interactions. Here, we describe 3DNetMod, a graph theory-based method for sensitive and accurate detection of chromatin domains across length scales in Hi-C data. We identify nested, partially overlapping TADs and subTADs genome wide by optimizing network modularity and varying a single resolution parameter. 3DNetMod can be applied broadly to understand genome reconfiguration in development and disease.
J.E.P.-C. is a New York Stem Cell Foundation (NYSCF) Robertson Investigator and an Alfred P. Sloan Foundation Fellow. This work was funded by The New York Stem Cell Foundation (J.E.P.-C.), the Alfred P. Sloan Foundation (J.E.P.-C.), the NIH Director's New Innovator Award (1DP2MH11024701; J.E.P.-C.), a 4D Nucleome Common Fund grant (1U01HL12999801; J.E.P.-C.) and a joint NSF-NIGMS grant to support research at the interface of the biological and mathematical sciences (1562665; J.E.P.-C.). This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under DGE-1321851 (H.N.). D.S.B. would also like to acknowledge support from the John D. and Catherine T. MacArthur Foundation.