Using activation status of signaling pathways as mechanism-based biomarkers to predict drug sensitivity

Sci Rep. 2015 Dec 18;5:18494. doi: 10.1038/srep18494.


Many complex traits, as drug response, are associated with changes in biological pathways rather than being caused by single gene alterations. Here, a predictive framework is presented in which gene expression data are recoded into activity statuses of signal transduction circuits (sub-pathways within signaling pathways that connect receptor proteins to final effector proteins that trigger cell actions). Such activity values are used as features by a prediction algorithm which can efficiently predict a continuous variable such as the IC50 value. The main advantage of this prediction method is that the features selected by the predictor, the signaling circuits, are themselves rich-informative, mechanism-based biomarkers which provide insight into or drug molecular mechanisms of action (MoA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Antineoplastic Agents / pharmacology*
  • Biomarkers / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Gene Expression / drug effects
  • Humans
  • Lethal Dose 50
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Phosphorylation / drug effects
  • Proteins / metabolism
  • Signal Transduction / drug effects*


  • Antineoplastic Agents
  • Biomarkers
  • Proteins