title: A complex network framework for unbiased statistical analyses of DNA-DNA contact maps.
abstract: Experimental techniques for the investigation of three-dimensional (3D) genome organization are being developed at a fast pace. Currently, the associated computational methods are mostly specific to the individual experimental approach. Here we present a general statistical framework that is widely applicable to the analysis of genomic contact maps, irrespective of the data acquisition and normalization processes. Within this framework DNA-DNA contact data are represented as a complex network, for which a broad number of directly applicable methods already exist. In such a network representation, DNA segments and contacts between them are denoted as nodes and edges, respectively. Furthermore, we present a robust method for generating randomized contact networks that explicitly take into account the inherent 3D nature of the genome and serve as realistic null-models for unbiased statistical analyses. By integrating a variety of large-scale genome-wide datasets we demonstrate that meiotic crossover sites display enriched genomic contacts and that cohesin-bound genes are significantly colocalized in the yeast nucleus. We anticipate that the complex network framework in conjunction with the randomization of DNA-DNA contact networks will become a widely used tool in the study of nuclear architecture.
authors.affiliation: Structural Studies Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK. kkruse@mrc-lmb.cam.ac.uk
authors.forename: Kai
authors.initials: K
authors.lastname: Kruse
authors.forename: Sven
authors.initials: S
authors.lastname: Sewitz
authors.forename: M Madan
authors.initials: MM
authors.lastname: Babu
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004271:DNA, Fungal / Q000737:chemistry; D003627:Data Interpretation, Statistical; D005800:Genes, Fungal; D016681:Genome, Fungal; D023281:Genomics / Q000379:methods*; D008540:Meiosis / Q000235:genetics; D009690:Nucleic Acid Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C119635:IRR1 protein, S cerevisiae