Discovering the genes mediating the interactions between chronic respiratory diseases in the human interactome

Biological networks are powerful resources for the discovery of potential candidate genes and for the investigation of the mechanisms underlying human complex disease like asthma and chronic obstructive pulmonary disease (COPD). Recent network-based computational studies have shown that disease genes encoding proteins have a strong tendency to interact with each other and to agglomerate in specific 'disease modules' identified as connected localized neighborhoods in the network [1]. In this scenario, perturbations originating within one disease module can diffuse through the network and affect other close diseases [2].
Recognizing the genes mediating such perturbations is crucial for understanding the biological pathways responsible for the comorbidity of similar diseases such as asthma and COPD. In this work, we identify the topological modules of these two diseases in the protein-protein interaction network and determine their mediators by defining a variant of betweenness centrality measure, called 'flow centrality'. The biological role of the observed flow central genes sheds light on the hypothesized common genetic origin of asthma and COPD [3].

[1] Barabasi et al., Nature Reviews Genetics (2011)
[2] Menche et al., Science (2015)
[3] Postma et al., JACI (2015)