Optimal Drug Prediction from Personal Genomics Profiles

Abstract

Cancer patients often show heterogeneous drug responses such that only a small subset of patients is sensitive to a given anticancer drug. With the availability of large-scale genomic profiling via next-generation sequencing, it is now economically feasible to profile the whole transcriptome and genome of individual patients in order to identify their unique genetic mutations and differentially expressed genes, which are believed to be responsible for heterogeneous drug responses. Although subtyping analysis has identified patient subgroups sharing common biomarkers, there is no effective method to predict the drug response of individual patients precisely and reliably. Herein, we propose a novel computational algorithm to predict the drug response of individual patients based on personal genomic profiles, as well as pharmacogenomic and drug sensitivity data. Specifically, more than 600 cancer cell lines (viewed as individual patients) across over 50 types of cancers and their responses to 75 drugs were obtained from the genomics of drug sensitivity in cancer database. The drug-specific sensitivity signatures were determined from the changes in genomic profiles of individual cell lines in response to a specific drug. The optimal drugs for individual cell lines were predicted by integrating the votes from other cell lines. The experimental results show that the proposed drug prediction algorithm can be used to improve greatly the reliability of finding optimal drugs for individual patients and will, thus, form a key component in the precision medicine infrastructure for oncology care.