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Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection

BACKGROUND: An enduring challenge in personalized medicine is to select right drug for individual patients. Testing drugs on patients in large clinical trials is one way to assess their efficacy and toxicity, but it is impractical to test hundreds of drugs currently under development. Therefore the...

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Autores principales: Dong, Zuoli, Zhang, Naiqian, Li, Chun, Wang, Haiyun, Fang, Yun, Wang, Jun, Zheng, Xiaoqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485860/
https://www.ncbi.nlm.nih.gov/pubmed/26121976
http://dx.doi.org/10.1186/s12885-015-1492-6
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author Dong, Zuoli
Zhang, Naiqian
Li, Chun
Wang, Haiyun
Fang, Yun
Wang, Jun
Zheng, Xiaoqi
author_facet Dong, Zuoli
Zhang, Naiqian
Li, Chun
Wang, Haiyun
Fang, Yun
Wang, Jun
Zheng, Xiaoqi
author_sort Dong, Zuoli
collection PubMed
description BACKGROUND: An enduring challenge in personalized medicine is to select right drug for individual patients. Testing drugs on patients in large clinical trials is one way to assess their efficacy and toxicity, but it is impractical to test hundreds of drugs currently under development. Therefore the preclinical prediction model is highly expected as it enables prediction of drug response to hundreds of cell lines in parallel. METHODS: Recently, two large-scale pharmacogenomic studies screened multiple anticancer drugs on over 1000 cell lines in an effort to elucidate the response mechanism of anticancer drugs. To this aim, we here used gene expression features and drug sensitivity data in Cancer Cell Line Encyclopedia (CCLE) to build a predictor based on Support Vector Machine (SVM) and a recursive feature selection tool. Robustness of our model was validated by cross-validation and an independent dataset, the Cancer Genome Project (CGP). RESULTS: Our model achieved good cross validation performance for most drugs in the Cancer Cell Line Encyclopedia (≥80 % accuracy for 10 drugs, ≥ 75 % accuracy for 19 drugs). Independent tests on eleven common drugs between CCLE and CGP achieved satisfactory performance for three of them, i.e., AZD6244, Erlotinib and PD-0325901, using expression levels of only twelve, six and seven genes, respectively. CONCLUSIONS: These results suggest that drug response could be effectively predicted from genomic features. Our model could be applied to predict drug response for some certain drugs and potentially play a complementary role in personalized medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1492-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-44858602015-07-01 Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection Dong, Zuoli Zhang, Naiqian Li, Chun Wang, Haiyun Fang, Yun Wang, Jun Zheng, Xiaoqi BMC Cancer Research Article BACKGROUND: An enduring challenge in personalized medicine is to select right drug for individual patients. Testing drugs on patients in large clinical trials is one way to assess their efficacy and toxicity, but it is impractical to test hundreds of drugs currently under development. Therefore the preclinical prediction model is highly expected as it enables prediction of drug response to hundreds of cell lines in parallel. METHODS: Recently, two large-scale pharmacogenomic studies screened multiple anticancer drugs on over 1000 cell lines in an effort to elucidate the response mechanism of anticancer drugs. To this aim, we here used gene expression features and drug sensitivity data in Cancer Cell Line Encyclopedia (CCLE) to build a predictor based on Support Vector Machine (SVM) and a recursive feature selection tool. Robustness of our model was validated by cross-validation and an independent dataset, the Cancer Genome Project (CGP). RESULTS: Our model achieved good cross validation performance for most drugs in the Cancer Cell Line Encyclopedia (≥80 % accuracy for 10 drugs, ≥ 75 % accuracy for 19 drugs). Independent tests on eleven common drugs between CCLE and CGP achieved satisfactory performance for three of them, i.e., AZD6244, Erlotinib and PD-0325901, using expression levels of only twelve, six and seven genes, respectively. CONCLUSIONS: These results suggest that drug response could be effectively predicted from genomic features. Our model could be applied to predict drug response for some certain drugs and potentially play a complementary role in personalized medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1492-6) contains supplementary material, which is available to authorized users. BioMed Central 2015-06-30 /pmc/articles/PMC4485860/ /pubmed/26121976 http://dx.doi.org/10.1186/s12885-015-1492-6 Text en © Dong et al. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Dong, Zuoli
Zhang, Naiqian
Li, Chun
Wang, Haiyun
Fang, Yun
Wang, Jun
Zheng, Xiaoqi
Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection
title Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection
title_full Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection
title_fullStr Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection
title_full_unstemmed Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection
title_short Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection
title_sort anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485860/
https://www.ncbi.nlm.nih.gov/pubmed/26121976
http://dx.doi.org/10.1186/s12885-015-1492-6
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