Inferring hidden causal relations between pathway members using reduced Google matrix of directed biological networks

Abstract

Signaling pathways represent parts of the global biological networkwhich connects them into a seamless whole through complex direct and indirect (hidden)crosstalk whose structure can change during normal development or in a pathological conditions such ascancer. Advanced methods for characterizing the structure of the globaldirected causal network can shed light on the mechanisms of global cellreprogramming changing the distribution of possible signaling flows.We suggest a methodology, called Googlomics, for the analysis of the structure of directedbiological networks using spectral analysis of their Google matrix.This approach uses parallels with quantum scattering theory, developed for processes in nuclear and mesoscopic physics and quantum chaos. We introduce the notion of reduced Google matrix in the context of the regulatory biological networks and demonstrate how its computation allows inferring hidden causal relations between the members of a signaling pathway or a functionally related group of genes.We investigate how the structure of hidden causal relationscan be reprogrammed as the result of changes in thetranscriptional network layer during cancerogenesis. The suggested Googlomics approach can be useful in various contexts for characterizing non-intuitive changesin the wiring of complex and large causal biological networks

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“…Finally we note that GMA allows to obtain interesting results for various types of directed networks including Wikipedia [13,14] and protein-protein interaction [15,16] networks.…”

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“…DeDaL provides a possibility to create data-driven and structure-driven network layouts, which are more insightful for grasping correlation patterns in multivariate data on top of networks [26]. ACSN module definitions were applied for testing a method for inferring hidden causal relations between pathway members using reduced Google matrix of directed biological networks [27].…”