Node Features of Chromosome Structure Network and Their Connections to Genome Annotation

The 3D conformations of chromosomes can encode biological significance, and its implication is being increasingly appreciated recently. Certain chromosome structural features, such as A/B compartmentalization, are frequently extracted from pairwise contact information (physical association between different regions of the genome) and compared with linear annotations of the genome, such as histone modifications and lamina association. Here, we investigate how additional properties of chromosome structure can be deduced using the abstract graph representation of the contact heatmap, and how network properties can have a better connection with some of these biological annotations. We constructed chromosome structure networks (CSNs) from bulk Hi-C data and calculated a set of site-resolved (node-based) network properties of these CSNs. We found these network properties are useful for characterizing chromosome structure features. We examined the ability of network properties in differentiating several scenarios, such as haploid vs diploid cells, partially inverted nuclei vs conventional architecture, and structural changes during cell development. We also examined the connection between network properties and a series of other linear annotations, such as histone modifications and chromatin states including poised promoter and enhancer labels. We found that semi-local network properties are more capable of characterizing genome annotations than diffusive or ultra-local node features. For example, local square clustering coefficient can be a strong classifier of lamina-associated domains (LADs), whereas a path-based network property, closeness centrality, does not vary concordantly with LAD status. We demonstrated that network properties can be useful for discerning large-scale chromosome structures that emerge in different biological situations. TOC Figure