Complementing Hi-C information for 3D chromatin reconstruction by ChromStruct

Abstract

A multiscale method proposed elsewhere for reconstructing plausible 3D configurations of the chromatin in cell nuclei is recalled, based on the integration of contact data from Hi-C experiments and additional information coming from ChIP-seq, RNA-seq and ChIA-PET experiments. Provided that the additional data come from independent experiments, this kind of approach is supposed to leverage them to complement possibly noisy, biased or missing Hi-C records. When the different data sources are mutually concurrent, the resulting solutions are corroborated; otherwise, their validity would be weakened. Here, a problem of reliability arises, entailing an appropriate choice of the relative weights to be assigned to the different informational contributions. A series of experiments is presented that help to quantify the advantages and the limitations offered by this strategy. Whereas the advantages in accuracy are not always significant, the case of missing Hi-C data demonstrates the effectiveness of additional information in reconstructing the highly packed segments of the structure.

Keywords: 3D chromatin configuration; DNA binding factors; Hi-C contact data; gene expression data; histone modification; modified bead-chain model; multiscale reconstruction algorithm.