Functional and transcriptional connectivity of communities in breast cancer co-expression networks

Transcriptional co-expression networks represent the concerted gene regulation programs by means of statistical inference of co-expression patterns. The rich phenomenology of transcriptional processes behind complex phenotypes such as cancer, is often captured (at least partially) in the connectivity structure of transcriptional co-expression networks. By analyzing the community structure of these networks, we may develop a deeper understanding of that phenomenology. We identified the modular structure of a transcriptional co-expression network obtained from breast cancer gene expression as well as a non-cancer adjacent breast tissue network as a control. We then analyzed the biological functions associated to the resulting communities by means of enrichment analysis. We also generated two projected networks for both, tumor and control networks: The first one is a projection to a network in which nodes are communities and edges represent topologically adjacent communities, indicating co-expression patterns between them. For the second projection, a bipartite network was generated containing a layer of modules and a layer of biological processes, with links between modules and the functions in which they are enriched; from this bipartite network, a projection to the community layer was obtained. From the analysis of the communities and projections, we were able to discern distinctive patterns of regulation between tumors and controls. Even though the connectivity structure of transcriptional co-expression networks is quite different, the topology of the projected networks is somehow similar, indicating functional compartmentalization, in both tumor and control conditions. However, the biological functions represented in the corresponding modules resulted notably different, with the tumor network comprising functional modules enriched for well-known hallmarks of cancer.