title: Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.
abstract: The personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and perform personalized anti-cancer therapy. Although the existing methods for patient-specific analysis have successfully uncovered crucial biomarkers, their performance takes a sudden turn for the worst in the presence of outliers, since the methods are based on non-robust manners. In practice, clinical and genomic alterations datasets usually contain outliers from various sources (e.g., experiment error, coding error, etc.) and the outliers may significantly affect the result of patient-specific analysis. We propose a robust methodology for patient-specific analysis in line with the NetwrokProfiler. In the proposed method, outliers in high dimensional gene expression levels and drug response datasets are simultaneously controlled by robust Mahalanobis distance in robust principal component space. Thus, we can effectively perform for predicting anti-cancer drug sensitivity and identifying sensitivity-specific biomarkers for individual patients. We observe through Monte Carlo simulations that the proposed robust method produces outstanding performances for predicting response variable in the presence of outliers. We also apply the proposed methodology to the Sanger dataset in order to uncover cancer biomarkers and predict anti-cancer drug sensitivity, and show the effectiveness of our method.
authors.affiliation: Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Heewon
authors.initials: H
authors.lastname: Park
authors.affiliation: Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Shimamura
authors.affiliation: Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
authors.affiliation: Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Imoto
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods*; D006801:Humans; D009010:Monte Carlo Method; D057285:Precision Medicine / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor