Gene essentiality and the topology of protein interaction networks

Abstract

The mechanistic bases for gene essentiality and for cell mutational resistance have long been disputed. The recent availability of large protein interaction databases has fuelled the analysis of protein interaction networks and several authors have proposed that gene dispensability could be strongly related to some topological parameters of these networks. However, many results were based on protein interaction data whose biases were not taken into account. In this article, we show that the essentiality of a gene in yeast is poorly related to the number of interactants (or degree) of the corresponding protein and that the physiological consequences of gene deletions are unrelated to several other properties of proteins in the interaction networks, such as the average degrees of their nearest neighbours, their clustering coefficients or their relative distances. We also found that yeast protein interaction networks lack degree correlation, i.e. a propensity for their vertices to associate according to their degrees. Gene essentiality and more generally cell resistance against mutations thus seem largely unrelated to many parameters of protein network topology.

Biological impacts and context of network theory

“…This result is often called the 'centrality-lethality' rule. Although recently debated (Coulomb et al, 2005), careful analyses strongly support the centrality-lethality rule (Batada et al, 2006).…”

A Survey on Evolutionary Analysis in PPI Networks

“…These findings were later supported by Gandhi et al (2006) who considered a set of PPI networks and also did not observe any significant relationship between a node degree and the essentiality of the corresponding protein. Interestingly, Coulomb et al (2005) did not test other centrality measures as betweenness and closeness, which showed a higher correlation with essentiality than just the simple degree (Hahn & Kern, 2005). Nevertheless, reaffirmed the existence of the correlation between the node degree and essentiality taking into account Coulomb et al's concerns.…”

“…Fraser et al, 2002;2003;Hahn & Kern, 2005;Jeong et al, 2001;Krylov et al, 2003). However Coulomb et al (2005) showed no correlation between essentiality and centrality, where centrality was assessed not only by the degree but also by higher order centrality measures, namely average neighbours' degree of a node and clustering coefficient of a node, suggesting that the correlation centrality-essentiality could be an artefact of the dataset. These findings were later supported by Gandhi et al (2006) who considered a set of PPI networks and also did not observe any significant relationship between a node degree and the essentiality of the corresponding protein.…”

Introduction to Systems Biology for Mathematical Programmers

“…The rationale for this question is that change to hub proteins might be constrained due to their interactions. While initial results were contradictory [18], a recent more decisive study [9] showed these results could be explained by subtle biases in the methods used to generate the PINs. After accounting for the equal density of active domains in hub and non-hub proteins, it was shown that there are not significant differences in mean rate of protein evolution.…”