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Predicting Anticancer Drug Response With Deep Learning Constrained by Signaling Pathways
Thanks to the availability of multiomics data of individual cancer patients, precision medicine or personalized medicine is becoming a promising treatment for individual cancer patients. However, the association patterns, that is, the mechanism of response (MoR) between large-scale multiomics featur...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581064/ https://www.ncbi.nlm.nih.gov/pubmed/36303766 http://dx.doi.org/10.3389/fbinf.2021.639349 |
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author | Zhang, Heming Chen, Yixin Li, Fuhai |
author_facet | Zhang, Heming Chen, Yixin Li, Fuhai |
author_sort | Zhang, Heming |
collection | PubMed |
description | Thanks to the availability of multiomics data of individual cancer patients, precision medicine or personalized medicine is becoming a promising treatment for individual cancer patients. However, the association patterns, that is, the mechanism of response (MoR) between large-scale multiomics features and drug response are complex and heterogeneous and remain unclear. Although there are existing computational models for predicting drug response using the high-dimensional multiomics features, it remains challenging to uncover the complex molecular mechanism of drug responses. To reduce the number of predictors/features and make the model more interpretable, in this study, 46 signaling pathways were used to build a deep learning model constrained by signaling pathways, consDeepSignaling, for anti–drug response prediction. Multiomics data, like gene expression and copy number variation, of individual genes can be integrated naturally in this model. The signaling pathway–constrained deep learning model was evaluated using the multiomics data of ∼1000 cancer cell lines in the Broad Institute Cancer Cell Line Encyclopedia (CCLE) database and the corresponding drug–cancer cell line response data set in the Genomics of Drug Sensitivity in Cancer (GDSC) database. The evaluation results showed that the proposed model outperformed the existing deep neural network models. Also, the model interpretation analysis indicated the distinctive patterns of importance of signaling pathways in anticancer drug response prediction. |
format | Online Article Text |
id | pubmed-9581064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95810642022-10-26 Predicting Anticancer Drug Response With Deep Learning Constrained by Signaling Pathways Zhang, Heming Chen, Yixin Li, Fuhai Front Bioinform Bioinformatics Thanks to the availability of multiomics data of individual cancer patients, precision medicine or personalized medicine is becoming a promising treatment for individual cancer patients. However, the association patterns, that is, the mechanism of response (MoR) between large-scale multiomics features and drug response are complex and heterogeneous and remain unclear. Although there are existing computational models for predicting drug response using the high-dimensional multiomics features, it remains challenging to uncover the complex molecular mechanism of drug responses. To reduce the number of predictors/features and make the model more interpretable, in this study, 46 signaling pathways were used to build a deep learning model constrained by signaling pathways, consDeepSignaling, for anti–drug response prediction. Multiomics data, like gene expression and copy number variation, of individual genes can be integrated naturally in this model. The signaling pathway–constrained deep learning model was evaluated using the multiomics data of ∼1000 cancer cell lines in the Broad Institute Cancer Cell Line Encyclopedia (CCLE) database and the corresponding drug–cancer cell line response data set in the Genomics of Drug Sensitivity in Cancer (GDSC) database. The evaluation results showed that the proposed model outperformed the existing deep neural network models. Also, the model interpretation analysis indicated the distinctive patterns of importance of signaling pathways in anticancer drug response prediction. Frontiers Media S.A. 2021-04-29 /pmc/articles/PMC9581064/ /pubmed/36303766 http://dx.doi.org/10.3389/fbinf.2021.639349 Text en Copyright © 2021 Zhang, Chen and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioinformatics Zhang, Heming Chen, Yixin Li, Fuhai Predicting Anticancer Drug Response With Deep Learning Constrained by Signaling Pathways |
title | Predicting Anticancer Drug Response With Deep Learning Constrained by Signaling Pathways |
title_full | Predicting Anticancer Drug Response With Deep Learning Constrained by Signaling Pathways |
title_fullStr | Predicting Anticancer Drug Response With Deep Learning Constrained by Signaling Pathways |
title_full_unstemmed | Predicting Anticancer Drug Response With Deep Learning Constrained by Signaling Pathways |
title_short | Predicting Anticancer Drug Response With Deep Learning Constrained by Signaling Pathways |
title_sort | predicting anticancer drug response with deep learning constrained by signaling pathways |
topic | Bioinformatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581064/ https://www.ncbi.nlm.nih.gov/pubmed/36303766 http://dx.doi.org/10.3389/fbinf.2021.639349 |
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