A network flow-based method to predict anticancer drug sensitivity

PLoS One. 2015 May 18;10(5):e0127380. doi: 10.1371/journal.pone.0127380. eCollection 2015.

Abstract

Predicting anticancer drug sensitivity can enhance the ability to individualize patient treatment, thus making development of cancer therapies more effective and safe. In this paper, we present a new network flow-based method, which utilizes the topological structure of pathways, for predicting anticancer drug sensitivities. Mutations and copy number alterations of cancer-related genes are assumed to change the pathway activity, and pathway activity difference before and after drug treatment is used as a measure of drug response. In our model, Contributions from different genetic alterations are considered as free parameters, which are optimized by the drug response data from the Cancer Genome Project (CGP). 10-fold cross validation on CGP data set showed that our model achieved comparable prediction results with existing elastic net model using much less input features.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Computational Biology / methods*
  • DNA Copy Number Variations
  • Gene Regulatory Networks / drug effects*
  • Genes, Neoplasm / drug effects
  • Humans
  • Models, Theoretical
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 31100953; XQZ) and the Program of Shanghai Normal University (DZL121; XQZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.