Community Structure Reveals Biologically Functional Modules in MEF2C Transcriptional Regulatory Network

Abstract

Gene regulatory networks are useful to understand the activity behind the complex mechanisms in transcriptional regulation. A main goal in contemporary biology is using such networks to understand the systemic regulation of gene expression. In this work, we carried out a systematic study of a transcriptional regulatory network derived from a comprehensive selection of all potential transcription factor interactions downstream from MEF2C, a human transcription factor master regulator. By analyzing the connectivity structure of such network, we were able to find different biologically functional processes and specific biochemical pathways statistically enriched in communities of genes into the network, such processes are related to cell signaling, cell cycle and metabolism. In this way we further support the hypothesis that structural properties of biological networks encode an important part of their functional behavior in eukaryotic cells.

Network Modularity in Breast Cancer Molecular Subtypes

“…Global organization patterns of large complex networks involve the presence of structural sub-units (subnetworks) that have been called communities or modules , broadly defined as subsets of tightly interconnected nodes so that the density of within-connections is higher than that of between-connections (Girvan and Newman, 2002 ; Porter et al, 2009 ; Fortunato, 2010 ). Module detection in networks, is still an open problem in computer science (Mucha et al, 2010 ) and there is an important variety of methods and algorithms to detect such communities (Gulbahce and Lehmann, 2008 ; Ahn et al, 2010 ; Fortunato, 2010 ; Xie et al, 2013 ; Fortunato and Hric, 2016 ); thus, modular structure is an issue of particular relevance, from economic and social systems (Espinal-Enríquez et al, 2015b ; García-Pérez et al, 2016 ), to biological systems (Alcalá-Corona et al, 2016 ).…”

“…In this sense, modules topology may capture some aspects of the phenomenology behind biological processes. Previous works have identified module detection as a valuable alternative for the identification of groups of genes that can associate biological features to phenotypes (Cantini et al, 2015 ; Alcalá-Corona et al, 2016 ). We followed along the lines of Alcalá-Corona et al ( 2016 ) looking to identify biologically functional modules.…”

“…Previous works have identified module detection as a valuable alternative for the identification of groups of genes that can associate biological features to phenotypes (Cantini et al, 2015 ; Alcalá-Corona et al, 2016 ). We followed along the lines of Alcalá-Corona et al ( 2016 ) looking to identify biologically functional modules. We were able to find subtype-specific functional processes in modules detected by using a random-walk based community detection algorithm (Rosvall and Bergstrom, 2008 ).…”

The Hierarchical Modular Structure of HER2+ Breast Cancer Network

“…Previously, we have shown that modular structures in transcriptional networks are usually associated with biological features (Alcalá-Corona et al, 2016 , 2017 ). Here we show that new insights on the biological features of HER2+ breast cancer may be revealed by exploring the functionality related to different layers of modularity.…”

“…We used the hierarchical map equation (Rosvall and Bergstrom, 2011 ) to find nested submodules into the HER2+ breast cancer network , and then, using the approach of Alcalá-Corona et al ( 2016 ), we identified whether those submodules were associated to a particular biological function. This section is divided as follows: network inference, differential expression analysis, modularity and submodularity detection and the hierarchical map equation, and functional analysis.…”