3D Chromatin structure estimation from chromosome conformation capture data

Caudai C., Salerno E., Zoppè M., Tonazzini A.

Chromatin  3D modeling  Chromosome Conformation  Capture 

In this communication we describe ChromStruct4, a method to reconstruct a set of plausible chromatin configurations starting from contact data obtained through Chromosome Conformation Capture techniques. Chromating fibre is modeled as a kinematic chain made of consecutive and partially penetrable beads whose properties (bead size, elasticity, curvature, etc.) can be suitably constrained. The chain can be divided in segments corresonding to Topological Association Domains. We do not search for a unique consensus configuration, because the experimental data are not derived from a single cell, but from millions of cells. We use a coarse-grained recoursive approach, based on a Simulated Annealing algorithm in order to sample the solution space. As opposed to most popular methods, we do not translate contact frequencies deterministically into distances, since this often produces structures that are not consistent with the Euclidean geometry, but adopt the assumption that loci with very high contact frequencies are actually close, but loci with low contact frequencies are not necessarily far away. ChromStruct4 is tested against real Hi-C data and compared with other methods for the 3-dimesional reconstruction fo Chromatin structure starting from Chromosome Conformation Capture data.

Source: BITS 2017 - 14th Annual Meeting of the Bioinformatics Italian Society, Cagliari, Italy, 5-7 July 2017