title: Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection.
abstract: BACKGROUND
  An enduring challenge in personalized medicine is to select right drug for individual patients. Testing drugs on patients in large clinical trials is one way to assess their efficacy and toxicity, but it is impractical to test hundreds of drugs currently under development. Therefore the preclinical prediction model is highly expected as it enables prediction of drug response to hundreds of cell lines in parallel.
  
  
  METHODS
  Recently, two large-scale pharmacogenomic studies screened multiple anticancer drugs on over 1000 cell lines in an effort to elucidate the response mechanism of anticancer drugs. To this aim, we here used gene expression features and drug sensitivity data in Cancer Cell Line Encyclopedia (CCLE) to build a predictor based on Support Vector Machine (SVM) and a recursive feature selection tool. Robustness of our model was validated by cross-validation and an independent dataset, the Cancer Genome Project (CGP).
  
  
  RESULTS
  Our model achieved good cross validation performance for most drugs in the Cancer Cell Line Encyclopedia (≥80% accuracy for 10 drugs, ≥75% accuracy for 19 drugs). Independent tests on eleven common drugs between CCLE and CGP achieved satisfactory performance for three of them, i.e., AZD6244, Erlotinib and PD-0325901, using expression levels of only twelve, six and seven genes, respectively.
  
  
  CONCLUSIONS
  These results suggest that drug response could be effectively predicted from genomic features. Our model could be applied to predict drug response for some certain drugs and potentially play a complementary role in personalized medicine.
authors.affiliation: Department of Mathematics, Shanghai Normal University, Shanghai, China. shnu_dzl@sina.com.
authors.forename: Zuoli
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Mathematics, Shanghai Normal University, Shanghai, China. naiqian@wfu.edu.cn.
authors.forename: Naiqian
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Mathematics, Bohai University, Jinzhou, China. lichwun@163.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai, China. wanghaiyun@tongji.edu.cn.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Mathematics, Shanghai Normal University, Shanghai, China. fangyun0919@shnu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Mathematics, Shanghai Normal University, Shanghai, China. jwang@shnu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Mathematics, Shanghai Normal University, Shanghai, China. zheng.shnu@gmail.com.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D057285:Precision Medicine; D060388:Support Vector Machine
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins