In silico perturbation of drug targets in pan-cancer analysis combining multiple networks and pathways

Gene. 2019 May 25:698:100-106. doi: 10.1016/j.gene.2019.02.064. Epub 2019 Mar 3.

Abstract

The knowledge of cancer cell response to conventional therapies is crucial in order to choose the correct therapy of patients affected by cancer. The major problem is generally attributed to the lack of specific biological processes able to predict the therapy efficacy. Here, we optimized a computational method for the analysis of gene networks able to detect and quantify the effects of a drug in a pan-cancer study. Overall, our method, using several network topological measures has identified a cancer gene network with a key role in biological processes. The gene network, able to classify with a good performance cancer vs normal samples, was modulated in silico to evaluate the effects of new or approved drugs. This computational model could offer an interesting hint to decipher molecular mechanisms contributing to resistance or inefficacy of drugs.

Keywords: Degree centrality; Drug; Gene-gene interaction; Machine learning; Network; Network efficiency; Pathway.

MeSH terms

  • Biomarkers, Pharmacological
  • Computational Biology / methods*
  • Computer Simulation
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Regulatory Networks / genetics
  • Gene Regulatory Networks / physiology
  • Humans
  • Machine Learning
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Protein Interaction Maps / genetics
  • Signal Transduction / genetics
  • Treatment Outcome

Substances

  • Biomarkers, Pharmacological