technical report Quantifying indirect effects among human disease genes


There is a lot of information on genes causing diseases, also on the total genome and proteome. A systems biological perspective makes it possible to evaluate the roles individual genes play (and their relative importance) in the context of the whole system. Based on the i2d and OMIM databases, we have constructed (1) a total human protein network, (2) a protein network of genes causing five selected diseases plus their interacting partners (IP) and (3) a protein network of these IPs. The five diseases were (1) various cancers, (2) heart diseases, (3) obesity, (4) autism and (5) diabetes. We have quantified the number and strength of IP network-mediated indirect effects between the five groups of disease genes and identified the most important mediators in the IP network. The main contribution of this work is twofold. We firstly illustrate that understanding the role and importance of individual genes highly depends on how to define the network of study. We secondly present new findings of the most important ``hidden mediators``: proteins seemingly unimportant but playing key roles in the mutual effects among diseases

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P. Nguyen,  F. Jordan