Systematic prediction of drug resistance caused by transporter genes in cancer cells

Abstract To study the drug resistance problem caused by transporters, we leveraged multiple large-scale public data sets of drug sensitivity, cell line genetic and transcriptional profiles, and gene silencing experiments. Through systematic integration of these data sets, we built various machine le...

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Autores principales:	Yao Shen, Zhipeng Yan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1b1666041b5b4e3fa52dc156b1a03cca
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spelling	oai:doaj.org-article:1b1666041b5b4e3fa52dc156b1a03cca2021-12-02T18:18:07ZSystematic prediction of drug resistance caused by transporter genes in cancer cells10.1038/s41598-021-86921-92045-2322https://doaj.org/article/1b1666041b5b4e3fa52dc156b1a03cca2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86921-9https://doaj.org/toc/2045-2322Abstract To study the drug resistance problem caused by transporters, we leveraged multiple large-scale public data sets of drug sensitivity, cell line genetic and transcriptional profiles, and gene silencing experiments. Through systematic integration of these data sets, we built various machine learning models to predict the difference between cell viability upon drug treatment and the silencing of its target across the same cell lines. More than 50% of the models built with the same data set or with independent data sets successfully predicted the testing set with significant correlation to the ground truth data. Features selected by our models were also significantly enriched in known drug transporters annotated in DrugBank for more than 60% of the models. Novel drug-transporter interactions were discovered, such as lapatinib and gefitinib with ABCA1, olaparib and NVPADW742 with ABCC3, and gefitinib and AZ628 with SLC4A4. Furthermore, we identified ABCC3, SLC12A7, SLCO4A1, SERPINA1, and SLC22A3 as potential transporters for erlotinib, three of which are also significantly more highly expressed in patients who were resistant to therapy in a clinical trial.Yao ShenZhipeng YanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yao Shen Zhipeng Yan Systematic prediction of drug resistance caused by transporter genes in cancer cells
description	Abstract To study the drug resistance problem caused by transporters, we leveraged multiple large-scale public data sets of drug sensitivity, cell line genetic and transcriptional profiles, and gene silencing experiments. Through systematic integration of these data sets, we built various machine learning models to predict the difference between cell viability upon drug treatment and the silencing of its target across the same cell lines. More than 50% of the models built with the same data set or with independent data sets successfully predicted the testing set with significant correlation to the ground truth data. Features selected by our models were also significantly enriched in known drug transporters annotated in DrugBank for more than 60% of the models. Novel drug-transporter interactions were discovered, such as lapatinib and gefitinib with ABCA1, olaparib and NVPADW742 with ABCC3, and gefitinib and AZ628 with SLC4A4. Furthermore, we identified ABCC3, SLC12A7, SLCO4A1, SERPINA1, and SLC22A3 as potential transporters for erlotinib, three of which are also significantly more highly expressed in patients who were resistant to therapy in a clinical trial.
format	article
author	Yao Shen Zhipeng Yan
author_facet	Yao Shen Zhipeng Yan
author_sort	Yao Shen
title	Systematic prediction of drug resistance caused by transporter genes in cancer cells
title_short	Systematic prediction of drug resistance caused by transporter genes in cancer cells
title_full	Systematic prediction of drug resistance caused by transporter genes in cancer cells
title_fullStr	Systematic prediction of drug resistance caused by transporter genes in cancer cells
title_full_unstemmed	Systematic prediction of drug resistance caused by transporter genes in cancer cells
title_sort	systematic prediction of drug resistance caused by transporter genes in cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1b1666041b5b4e3fa52dc156b1a03cca
work_keys_str_mv	AT yaoshen systematicpredictionofdrugresistancecausedbytransportergenesincancercells AT zhipengyan systematicpredictionofdrugresistancecausedbytransportergenesincancercells
_version_	1718378260698497024

Systematic prediction of drug resistance caused by transporter genes in cancer cells

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