Integrating Domain Specific Knowledge and Network Analysis to Predict Drug Sensitivity of Cancer Cell Lines.
One of fundamental challenges in cancer studies is that varying molecular characteristics of different tumor types may lead to resistance to certain drugs. As a result, the same drug can lead to significantly different results in different types of cancer thus emphasizing the need for individualized medicine. Individual prediction of drug response has great potential to aid in improving the clinical outcome and reduce the financial costs associated with prescribing chemotherapy drugs to which the patient's tumor might be resistant. In this paper we develop a network based classifier (NBC) method for predicting sensitivity of cell lines to anticancer drugs from transcriptome data. In the literature, this strategy has been used for predicting cancer types. Here, we extend it to estimate sensitivity of cells from different tumor types to various anticancer drugs. Furthermore, we incorporate domain specific knowledge such as the use of apoptotic gene list and clinical dose information in our method to impart biological significance to the prediction. Our experimental results suggest that our network based classifier (NBC) method outperforms existing classifiers in estimating sensitivity of cell lines for different drugs.
Department of Computer and Information Science and Engineering, University of Florida, Gainesville, FL, United States of America.
Sebo
S
Kim
Department of Molecular Genetics and Microbiology College of Medicine, University of Florida, Gainesville, FL, United States of America.
Varsha
V
Sundaresan
Department of Molecular Genetics and Microbiology College of Medicine, University of Florida, Gainesville, FL, United States of America.
Lei
L
Zhou
Department of Computer and Information Science and Engineering, University of Florida, Gainesville, FL, United States of America.
Tamer
T
Kahveci
D000465:Algorithms; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D019992:Databases as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D053263:Gene Regulatory Networks; D006801:Humans; D019359:Knowledge; D012372:ROC Curve
D000970:Antineoplastic Agents