Perspectives for the reconstruction of 3D chromatin conformation using single cell Hi-C data.

Construction of chromosomes 3D models based on single cell Hi-C data constitute an important challenge. We present a reconstruction approach, DPDchrom, that incorporates basic knowledge whether the reconstructed conformation should be coil-like or globular and spring relaxation at contact sites. In...

Description complète

Enregistré dans:
Détails bibliographiques
Auteurs principaux: Pavel I Kos, Aleksandra A Galitsyna, Sergey V Ulianov, Mikhail S Gelfand, Sergey V Razin, Alexander V Chertovich
Format: article
Langue:EN
Publié: Public Library of Science (PLoS) 2021
Sujets:
Accès en ligne:https://doaj.org/article/bf9ef8a3ca1c4ad0bd894ed8ee553a32
Tags: Ajouter un tag
Pas de tags, Soyez le premier à ajouter un tag!
Description
Résumé:Construction of chromosomes 3D models based on single cell Hi-C data constitute an important challenge. We present a reconstruction approach, DPDchrom, that incorporates basic knowledge whether the reconstructed conformation should be coil-like or globular and spring relaxation at contact sites. In contrast to previously published protocols, DPDchrom can naturally form globular conformation due to the presence of explicit solvent. Benchmarking of this and several other methods on artificial polymer models reveals similar reconstruction accuracy at high contact density and DPDchrom advantage at low contact density. To compare 3D structures insensitively to spatial orientation and scale, we propose the Modified Jaccard Index. We analyzed two sources of the contact dropout: contact radius change and random contact sampling. We found that the reconstruction accuracy exponentially depends on the number of contacts per genomic bin allowing to estimate the reconstruction accuracy in advance. We applied DPDchrom to model chromosome configurations based on single-cell Hi-C data of mouse oocytes and found that these configurations differ significantly from a random one, that is consistent with other studies.