TY - JOUR T1 - Integrative pharmacogenomics to infer large-scale drug taxonomy JF - bioRxiv DO - 10.1101/046219 SP - 046219 AU - Nehme El-Hachem AU - Deena M.A. Gendoo AU - Laleh Soltan Ghoraie AU - Zhaleh Safikhani AU - Petr Smirnov AU - Ruth Isserlin AU - Gary D. Bader AU - Anna Goldenberg AU - Benjamin Haibe-Kains Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/10/21/046219.abstract N2 - Identification of drug targets and mechanism of action (MoA) for new and uncharacterized drugs is important for optimization of drug efficacy. Current MoA prediction approaches largely rely on prior information including side effects, therapeutic indication and/or chemo-informatics. Such information is not transferable or applicable for newly identified, previously uncharacterized small molecules. Therefore, a shift in the paradigm of MoA predictions is necessary towards development of unbiased approaches that can elucidate drug relationships and efficiently classify new compounds with basic input data. We propose a new integrative computational pharmacogenomic approach, referred to as Drug Network Fusion (DNF), to infer scalable drug taxonomies that relies only on basic drug characteristics towards elucidating drug-drug relationships. DNF is the first framework to integrate drug structural information, high-throughput drug perturbation and drug sensitivity profiles, enabling drug classification of new experimental compounds with minimal prior information. We demonstrate that the DNF taxonomy succeeds in identifying pertinent and novel drug-drug relationships, making it suitable for investigating experimental drugs with potential new targets or MoA. We highlight how the scalability of DNF facilitates identification of key drug relationships across different drug categories, and poses as a flexible tool for potential clinical applications in precision medicine. Our results support DNF as a valuable resource to the cancer research community by providing new hypotheses on the compound MoA and potential insights for drug repurposing. ER -