MMDRP: drug response prediction and biomarker discovery using multi-modal deep learning.

Motivation: A major challenge in cancer care is that patients with similar demographics, tumor types, and medical histories can respond quite differently to the same drug regimens. This difference is largely explained by genetic and other molecular variabilities among the patients and their cancers. Efforts in the pharmacogenomics field are underway to understand better the relationship between the genome of the patient's healthy and tumor cells and their response to therapy. To advance this goal, research groups and consortia have undertaken large-scale systematic screening of panels of drugs across multiple cancer cell lines that have been molecularly profiled by genomics, proteomics, and similar techniques. These large data drug screening sets have been applied to the problem of drug response prediction (DRP), the challenge of predicting the response of a previously untested drug/cell-line combination. Although deep learning algorithms outperform traditional methods, there are still many challenges in DRP that ultimately result in these models' low generalizability and hampers their clinical application. Results: In this article, we describe a novel algorithm that addresses the major shortcomings of current DRP methods by combining multiple cell line characterization data, addressing drug response data skewness, and improving chemical compound representation. Availability and implementation: MMDRP is implemented as an open-source, Python-based, command-line program and is available at https://github.com/LincolnSteinLab/MMDRP.