Relationship between spatial organization and biological function, analyzed using gene ontology and chromosome conformation capture of human and fission yeast genomes

Abstract

Cells regulate functionally related genes cis- and trans-contacts in order to perform specific biological roles. To understand the cryptic spatial genomic contexts underlying these biological functions, we analyzed the gene association data from the gene ontology (GO) database and the genomic spatial organization data obtained by analysis of chromosome conformation capture (3C)-based data from the Sequence Read Archive, where GO and 3C-based data were used to measure functional similarity and spatial proximity, respectively, between genomic loci. In the human genome and the fission yeast genome, we observed that correlation between the two measures was statistically significant on a genome-wide scale. Specifically, it is also confirmed that the genomic spatial architecture is affected by functional similarity of genes by showing better correlation of functional similarities with spatial distances estimated by contact frequencies than those estimated by genomic distances for cis-contacts. Furthermore, we analyzed distances between the genomic segments sharing the same GO term using the two-sample t test, found that the genomic segments identified by various GO terms are spatially located closer than the average distance over statistically-valid contacts, and provided a list of the GO terms. The results suggested that genomic loci with similar biological functions are situated in close proximity to each other in the nuclear space by aggregating functionally related genes in a short spatial range