3D Genome Reconstruction with ShRec3D+ and Hi-C Data

Abstract

Hi-C technology, a chromosome conformation capture (3C) based method, has been developed to capture genome-wide interactions at a given resolution. The next challenge is to reconstruct 3D structure of genome from the 3C-derived data computationally. Several existing methods have been proposed to obtain a consensus structure or ensemble structures. These methods can be categorized as probabilistic models or restraint-based models. In this paper, we propose a method, named ShRec3D+, to infer a consensus 3D structure of a genome from Hi-C data. The method is a two-step algorithm which is based on ChromSDE and ShRec3D methods. First, correct the conversion factor by golden section search for converting interaction frequency data to a distance weighted graph. Second, apply shortest-path algorithm and multi-dimensional scaling (MDS) algorithm to compute the 3D coordinates of a set of genomic loci from the distance graph. We validate ShRec3D+ accuracy on both simulation data and publicly Hi-C data. Our test results indicate that our method successfully corrects the parameter with a given resolution, is more accurate than ShRec3D, and is more efficient and robust than ChromSDE.