Uncovering disease-disease relationships through the incomplete interactome

J. Menche, A. Sharma, M. Kitsak, D. Ghiassian, M. Vidal, J. Loscazlo, A.-L. Barabasi
Science
347:6224, 1257601-1 (2015).
February 20, 2015

Abstract

According to the  disease module hypothesis, the cellular components associated with a disease  segregate in the same neighborhood of the human interactome, the map of  biologically relevant molecular interactions. Yet, given the incompleteness  of the interactome and the limited knowledge of disease-associated genes, it  is not obvious if the available data have sufficient coverage to map out  modules associated with each disease. Here we derive mathematical conditions  for the identifiability of disease modules and show that the network-based  location of each disease module determines its pathobiological relationship  to other diseases. For example, diseases with overlapping network modules  show significant coexpression patterns, symptom similarity, and comorbidity,  whereas diseases residing in separated network neighborhoods are  phenotypically distinct. These tools represent an interactome-based platform  to predict molecular commonalities between phenotypically related diseases,  even if they do not share primary disease genes.

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