BRCA-Monet: A breast cancer specific drug treatment mode-of-action network for treatment effective prediction using large scale microarray database

Chifeng Ma, Hung I.H. Chen, Mario Flores, Yufei Huang, Yidong Chen

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background: Connectivity map (cMap) is a recent developed dataset and algorithm for uncovering and understanding the treatment effect of small molecules on different cancer cell lines. It is widely used but there are still remaining challenges for accurate predictions.Method: Here, we propose BRCA-MoNet, a network of drug mode of action (MoA) specific to breast cancer, which is constructed based on the cMap dataset. A drug signature selection algorithm fitting the characteristic of cMap data, a quality control scheme as well as a novel query algorithm based on BRCA-MoNet are developed for more effective prediction of drug effects.Result: BRCA-MoNet was applied to three independent data sets obtained from the GEO database: Estrodial treated MCF7 cell line, BMS-754807 treated MCF7 cell line, and a breast cancer patient microarray dataset. In the first case, BRCA-MoNet could identify drug MoAs likely to share same and reverse treatment effect. In the second case, the result demonstrated the potential of BRCA-MoNet to reposition drugs and predict treatment effects for drugs not in cMap data. In the third case, a possible procedure of personalized drug selection is showcased.Conclusions: The results clearly demonstrated that the proposed BRCA-MoNet approach can provide increased prediction power to cMap and thus will be useful for identification of new therapeutic candidates.Website: The web based application is developed and can be access through the following link http://compgenomics.utsa.edu/BRCAMoNet/.

Original languageEnglish (US)
Article numberS5
JournalBMC Systems Biology
Volume7
Issue numberSUPPL 5
DOIs
StatePublished - Dec 9 2013

Keywords

  • Breast Cancer Mode of Action Network (BRCA-MoNet)
  • Connectivity Map
  • Mode of Action (MoA)

ASJC Scopus subject areas

  • Structural Biology
  • Modeling and Simulation
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

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