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Using protein interaction networks to understand complex diseases
Koyutürk M. Computer45 (3):31-38,2012.Type:Article
Date Reviewed: Oct 18 2012

Koyutürk centers his discussion on the opportunity to focus on protein-to-protein interaction (PPI) networks rather than on classical enrichment analysis methods to discover dysregulated genes related to complex diseases. Interestingly, he grounds his discussion on the true assertion that “differential gene expression in several complex diseases shows that dysregulated genes in similar diseases are likely to interact with each other in PPI networks,” and hence that “network-based analyses of differential expression can prove more promising than pathway-based analyses in discovering novel relationships among genes in the context of disease mechanisms.”

The author explores some areas of research where scientists have developed new algorithms to find dysregulated networks. Some have capitalized on the identification of “connected subgraphs of the PPI network with a high aggregate significance in the differential gene expression.” Against the intractable computational complexity of this task, the author proposes some alternative heuristics. In particular, he presents two new concepts: “coordinate dysregulation to assess the synergistic dysregulation among two or more genes,” and combinatorial coordinate dysregulation to “capture the combinatorial relationship in the dysregulation of multiple interacting genes.” These arguments are, unfortunately, badly presented due to the fill-in-the-blanks mathematics, which, although simple, is poorly described and does not contribute more information than the words already provide. The tone of the discussion decidedly improves with the introduction of discriminative subnetworks, as alternate tools “to discriminate phenotype and control within the framework of a specific classification technique.” Such a framework appears useful in identifying drug targets, and “in developing detailed dynamic models for disease mechanisms.”

Overall, I found the paper pleasant to read and interesting. The author focuses on the important point that complex human diseases should be studied from a systemic standpoint. That is, diseases should be seen as the result of the (wrong) “interplay of multiple genetic and environmental factors”. I agree with this.

Reviewer:  Tommaso Mazza Review #: CR140609 (1302-0152)
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Biology And Genetics (J.3 ... )
 
 
Graphs And Networks (E.1 ... )
 
 
Graph Theory (G.2.2 )
 
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