title: Identification of gene-drug interactions that impact patient survival in TCGA.
abstract: BACKGROUND
  With the advent of large scale biological data collection for various diseases, data analysis pipelines and workflows need to be established to build frameworks for integrative analysis. Here the authors present a pipeline for identifying disease specific gene-drug interactions using CNV (Copy Number Variation) and clinical data from the TCGA (The Cancer Genome Atlas) project. Two cancer types were selected for analysis, LGG (Brain lower grade glioma) and GBM (Glioblastoma multiforme), due to the possible progression from LGG to GBM in some cases. The copy number and clinical data were then used to preform survival analysis on a gene by gene basis on sub-populations of patients exposed to a given drug.
  
  
  RESULTS
  Several gene-drug interactions are identified, where the copy number of a gene is associated to survival of a patient exposed to a certain drug. Both Irinotecan/HAS2 (Hyaluronan synthase 2) and Bevacizumab/PGAM1 (Phosphoglycerate mutase 1) are interactions found in this study with independent confirmation. Independent work in colon, breast cancer and leukemia (Györffy, Breast Cancer Res Treat 123:725-731, 2010; Mueller, Mol Cancer Ther 11:3024-3032, 2010; Hitosugi, Cancer Cell 13:585-600, 2012) showed these two interactions can lead to increased survival.
  
  
  CONCLUSIONS
  While the pipeline produced several possible interactions where increased survival is linked to normal or increased copy number of a given gene for patients treated with a given drug, no instance of low copy number or full deletion was linked to increased survival. The development of this pipeline shows a promising utility to identify possible beneficial gene-drug interactions that could improve patient survival and may illustrate some of the problems inherent in this kind of analysis on these data.
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Dr. NW, Atlanta, GA, 30332, USA. John.spainhour@bme.gatech.edu.
authors.forename: John Christian Givhan
authors.initials: JC
authors.lastname: Spainhour
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Dr. NW, Atlanta, GA, 30332, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Qiu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D056915:DNA Copy Number Variations / Q000235:genetics*; D004347:Drug Interactions / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D012984:Software; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents
keywords: Gene-drug interaction; Survival; TCGA