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Machine learning approach informs biology of cancer drug response
Journal article   Open access   Peer reviewed

Machine learning approach informs biology of cancer drug response

Eliot Y Zhu and Adam J Dupuy
BMC bioinformatics, Vol.23(1), pp.184-184
05/17/2022
DOI: 10.1186/s12859-022-04720-z
PMCID: PMC9112473
PMID: 35581546
url
https://doi.org/10.1186/s12859-022-04720-zView
Published (Version of record) Open Access

Abstract

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. 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 BRAF . We apply our approach to reveal determinants of drug resistance to microtubule inhibitors. 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. Our results demonstrate the utility of combining informed feature selection and machine learning algorithms in understanding cancer drug response.
Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Biology Cell Line, Tumor Humans Machine Learning Melanoma - metabolism Proto-Oncogene Proteins B-raf

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