title: BRCA-Monet: a breast cancer specific drug treatment mode-of-action network for treatment effective prediction using large scale microarray database.
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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.forename: Chifeng
authors.initials: C
authors.lastname: Ma
authors.forename: Hung-I
authors.initials: HI
authors.lastname: Chen
authors.forename: Mario
authors.initials: M
authors.lastname: Flores
authors.forename: Yufei
authors.initials: Y
authors.lastname: Huang
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D061986:MCF-7 Cells; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014227:Triazines / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; C545990:BMS 754807; D011720:Pyrazoles; D014227:Triazines; D004958:Estradiol