Author:
Zhu Eliot Y.,Dupuy Adam J.
Abstract
Abstract
Background
The mechanism of action for most cancer drugs is not clear. Large-scale pharmacogenomic cancer cell line datasets offer a rich resource to obtain this knowledge. Here, we present an analysis strategy for revealing biological pathways that contribute to drug response using publicly available pharmacogenomic cancer cell line datasets.
Methods
We present a custom machine-learning based approach for identifying biological pathways involved in cancer drug response. We test the utility of our approach with a pan-cancer analysis of ML210, an inhibitor of GPX4, and a melanoma-focused analysis of inhibitors of BRAFV600. We apply our approach to reveal determinants of drug resistance to microtubule inhibitors.
Results
Our method implicated lipid metabolism and Rac1/cytoskeleton signaling in the context of ML210 and BRAF inhibitor response, respectively. These findings are consistent with current knowledge of how these drugs work. For microtubule inhibitors, our approach implicated Notch and Akt signaling as pathways that associated with response.
Conclusions
Our results demonstrate the utility of combining informed feature selection and machine learning algorithms in understanding cancer drug response.
Publisher
Springer Science and Business Media LLC
Subject
Applied Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Structural Biology
Cited by
6 articles.
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