A methodology for detecting the orthology signal in a PPI network at a functional complex level

Abstract

BackgroundStable evolutionary signal has been observed in a yeast protein-protein interaction (PPI) network. These finding suggests more connected regions of a PPI network to be potential mediators of evolutionary information. Because more connected regions of PPI networks contain functional complexes, we are motivated to exploit the orthology relation for identifying complexes that can be clearly attributed to such evolutionary signal.ResultsWe proposed a computational methodology for detecting the orthology signal present in a PPI network at a functional complex level. Specifically, we examined highly functionally coherent putative protein complexes as detected by a clustering technique in the complete yeast PPI network, in the yeast sub-network which spans only ortholog proteins as determined by a given second organism, and in yeast sub-networks induced by a set of proteins randomly selected. We proposed a filtering technique for extracting orthology-driven clusters with unique functionalities, that is, neither enriched by clusters identified using the complete yeast PPI network nor identified using random sampling. Moreover, we extracted functional categories that can be clearly attributed to the presence of evolutionary signal as described by these clusters.ConclusionsApplication of the proposed methodology to the yeast PPI network indicated that evolutionary information at a functional complex level can be retrieved from the structure of the network. In particular, we detected protein complexes whose functionality could be uniquely attributed to the evolutionary signal. Moreover, we identified functions that are over-represented in these complexes due the evolutionary signal.

A Survey on Evolutionary Analysis in PPI Networks

“…This suggests that presence of evolution in modularity of PPI networks is more versatile and flexible with different degrees of conservation. The findings of Jancura et al (2011) seem to conform with related studies that focused on evolutionary cohesiveness of protein functional modules in order to investigate whether a group of proteins which functionally interact, co-evolve more cohesively than a random group of proteins. Either known protein complexes and pathways were analysed (Fokkens & Snel, 2009;Seidl & Schultz, 2009;Snel & Huynen, 2004) or putative protein modules usually derived from integrated networks of functional link evidences (Campillos et al, 2006;Zhao et al, 2007;Zinman et al, 2011).…”

“…The finding that modularity of PPI networks is constrained by evolution and that conserved interactions are enriched in dense motifs and regions of a PPI network also suggest that protein complexes present in such cohesive areas should be evolutionary driven (Jancura et al, 2011). As putative protein complexes can be extracted from a PPI network by means of clustering techniques, Jancura et al (2011) detected such protein complexes in the PPI network consisting of only yeast proteins having an ortholog in another organism and compared them with those protein complexes derived either by using the global topology of a yeast PPI network or by using a network induced by randomly selected proteins. The in-depth examination of enriched functions in these three types of protein complexes revealed that evolutionary-driven complexes are functionally well differentiated from other two types of protein complexes found in the same interaction data.…”

Robustness evaluation of Evolutionary-based complex detection algorithms for protein interaction networks with negative control

“…In the PPI networks, the detection of protein complexes, or functional modules, is an ongoing challenge, but it is crucial for revealing the mechanism of biological functions and providing a valuable guide for comprehending the processes controlling cell life. In addition, detecting protein complexes can be useful for defining the evolutionary orthology signal, such as for the prediction of protein functions based on their biological functions that have not yet been identified, and most crucially, for medical uses [9,10]. It is noteworthy to mention that proteins that interact with one another can be categorized as either "protein complexes" or "functional modules," each of which having a distinct biological significance.…”

Human SIRT1 Multispecificity Is Modulated by Active-Site Vicinity Substitutions during Natural Evolution

“…Protein–protein interaction (PPI) networks in multicellular organisms, such as humans, often include a larger number of cellular proteins relative to networks found in monocellular eukaryotic organisms ( Evlampiev and Isambert 2008 ; Jancura et al. 2012 ; Jin et al.…”