title: On the demultiplexing of chromosome capture conformation data.
abstract: How to describe the multiple chromosome structures that underlie interactions among genome loci and how to quantify the occurrence of these structures in a cell population remain important challenges to solve, which can be addressed via a proper demultiplexing of chromosome capture conformation related data. Here, we first aim to review two main methodologies that have been proposed to tackle this problem: restrained-based methods, in which the resulting chromosome structures stem from the multiple solutions of a distance satisfaction problem; and thermodynamic-based methods, in which the structures stem from the simulation of polymer models. Next, we propose a novel demultiplexing method based on a matrix decomposition of contact maps. To this end, we extend the notion of topologically associated domains (TADs) by introducing that of statistical interaction domains (SIDs). SIDs can overlap and occur in a cell population at certain frequencies, and we propose a simple method to estimate these frequency values. As an application, we show that SIDs that measure 100kb to tens of Mb long occur both frequently and specifically in the human genome.
authors.affiliation: Laboratoire Adaptation et Pathogénie des Micro-organismes - UMR 5163, Université Grenoble 1, CNRS, BP 170, F-38042 Grenoble Cedex 9, France; Gene Regulacion, Stem Cells, and Cancer Program, Centre de Regulaciò Genòmica (CRG), 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain. Electronic address: ivan.junier@ujf-grenoble.fr.
authors.forename: Ivan
authors.initials: I
authors.lastname: Junier
authors.affiliation: Gene Regulacion, Stem Cells, and Cancer Program, Centre de Regulaciò Genòmica (CRG), 08003 Barcelona, Spain; Genome Biology Group, Centre Nacional d'Anàlisi Genòmica (CNAG), 08028 Barcelona, Spain.
authors.forename: Yannick G
authors.initials: YG
authors.lastname: Spill
authors.affiliation: Gene Regulacion, Stem Cells, and Cancer Program, Centre de Regulaciò Genòmica (CRG), 08003 Barcelona, Spain; Genome Biology Group, Centre Nacional d'Anàlisi Genòmica (CNAG), 08028 Barcelona, Spain.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Marti-Renom
authors.affiliation: Gene Regulacion, Stem Cells, and Cancer Program, Centre de Regulaciò Genòmica (CRG), 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Beato
authors.affiliation: Gene Regulacion, Stem Cells, and Cancer Program, Centre de Regulaciò Genòmica (CRG), 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: François
authors.initials: F
authors.lastname: le Dily
mesh_terms: D000465:Algorithms; D000818:Animals; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic
keywords: Deconvolution; Demultiplexing; Genomic contact maps; Polymer models of chromosomes; Restrained-based methods