Aggregated network centrality shows non-random structure of genomic and proteomic networks

Abstract

Network analysis is a powerful tool for modelling biological systems. We propose a new approach that integrates the genomic interaction data at population level with the proteomic interaction data. In our approach we use chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) data from human genome to construct a set of genomic interaction networks, considering the natural partitioning of chromatin into chromatin contact domains (CCD). The genomic networks are then mapped onto proteomic interactions, to create protein-protein interaction (PPI) subnetworks. Furthermore, the network-based topological properties of these proteomic subnetworks are investigated, namely closeness centrality, betweenness centrality and clustering coefficient. We statistically confirm, that networks identified by our method significantly differ from random networks in these network properties. Additionally, we identify one of the regions, namely chr6:32014923-33217929, as having an above-random concentration of the single nucleotide polymorphisms (SNPs) related to autoimmune diseases. Then we present it in the form of a meta-network, which includes multi-omic data: genomic contact sites (anchors), genes, proteins and SNPs. Using this example we demonstrate, that the created networks provide a valid mapping of genes to SNPs, expanding on the raw SNP dataset used.

Keywords: Centrality; Chromatin contact domains; Chromatin interaction; Meta-network; Network analysis; Protein-protein interaction.