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

PLoS One. 2018 Jan 25;13(1):e0190812. doi: 10.1371/journal.pone.0190812. eCollection 2018.

Abstract

Signaling pathways represent parts of the global biological molecular network which connects them into a seamless whole through complex direct and indirect (hidden) crosstalk whose structure can change during development or in pathological conditions. We suggest a novel methodology, called Googlomics, for the structural analysis of directed biological networks using spectral analysis of their Google matrices, using parallels with quantum scattering theory, developed for nuclear and mesoscopic physics and quantum chaos. We introduce analytical "reduced Google matrix" method for the analysis of biological network structure. The method 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 relations can be reprogrammed as a result of changes in the transcriptional network layer during cancerogenesis. The suggested Googlomics approach rigorously characterizes complex systemic changes in the wiring of large causal biological networks in a computationally efficient way.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Causality
  • Cell Line
  • Computational Biology
  • Databases, Protein / statistics & numerical data
  • Gene Regulatory Networks*
  • Humans
  • K562 Cells
  • Models, Biological*
  • Models, Genetic
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Quantum Theory
  • Search Engine*
  • Signal Transduction / genetics*
  • Signal Transduction / physiology*
  • Stochastic Processes

Substances

  • Neoplasm Proteins

Grants and funding

This research is supported by the MASTODONS-2016 CNRS project APLIGOOGLE (see http://www.quantware.ups-tlse.fr/APLIGOOGLE/). AZ was supported by the Ministry of education and science of Russia (Project No. 14.Y26.31.0022). There was no additional external funding received for this study.