Statistical properties of the MetaCore network of protein\u2013protein interactions

Abstract

The MetaCore commercial database describes interactions of proteins and other chemical molecules and clusters in the form of directed network between these elements, viewed as nodes. The number of nodes goes beyond 40 thousands with almost 300 thousands links between them. The links have essentially bi-functional nature describing either activation or inhibition actions between proteins. We present here the analysis of statistical properties of this complex network applying the methods of the Google matrix, PageRank and CheiRank algorithms broadly used in the frame of the World Wide Web, Wikipedia, the world trade and other directed networks. We specifically describe the Ising PageRank approach which allows to treat the bi-functional type of protein–protein interactions. We also show that the developed reduced Google matrix algorithm allows to obtain an effective network of interactions inside a specific group of selected proteins. In addition to already known direct protein–protein interactions, this method allows to infer non trivial and unknown interactions between proteins arising from the summation over all the indirect pathways passing via the global bi-functional network. The developed analysis allows to establish an average action of each protein being more oriented to activation or inhibition. We argue that the described Google matrix analysis represents an efficient tool for investigation of influence of specific groups of proteins related to specific diseases.