High-throughput drug sensitivity testing provides a powerful phenotypic profiling approach to identify effective drug candidates for individual cell lines or patient-derived samples. Here, we describe an experimental-computational pipeline, named target addiction scoring (TAS), which mathematically transforms the drug response profiles into target addiction signatures, and thereby provides a ranking of potential therapeutic targets according to their functional importance in a particular cancer sample. The TAS pipeline makes use of drug polypharmacology to integrate the drug sensitivity and selectivity profiles through systems-wide interconnection networks between drugs and their targets, including both primary protein targets as well as secondary off-targets. We show how the TAS pipeline enables one to identify not only single-target addictions but also combinatorial coaddictions among targets that often underlie synergistic drug combinations.
CITATION STYLE
Jaiswal, A., Yadav, B., Wennerberg, K., & Aittokallio, T. (2019). Integrated analysis of drug sensitivity and selectivity to predict synergistic drug combinations and target coaddictions in cancer. In Methods in Molecular Biology (Vol. 1888, pp. 205–217). Humana Press Inc. https://doi.org/10.1007/978-1-4939-8891-4_12
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