Network concepts for analyzing 3D genome structure from chromosomal contact maps

Background: The recent experimental technique of chromosome conformational capture gives an in-vivo access to pairwise contact frequencies between genomic loci. We present how network analysis can be exploited to extract information from genome-wide contact maps. Methods: We recently proposed to use graph distance for deriving a complete distance matrix from sparse contact maps. Completed with multidimensional scaling (MDS), this network-based method provided a fast algorithm, ShRec3D, for reconstructing 3D genome structures. Results: We here develop an extension of this algorithm, by devising a tunable variant of the graph distance and introducing an alternative implementation of multidimensional scaling. This extended algorithm is shown to be more flexible so as to accommodate additional experimental constraints, focus on specific spatial scales, and produce tractable representations of human data. Conclusions: Network representation of genomic contacts offers a path where physical and systemic approaches are joined to unravel the biological role of the 3D genome structure.