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ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs

Single-cell RNA sequencing technology has enabled in-depth analysis of intercellular heterogeneity in various diseases. However, its full potential for precision medicine has yet to be reached. Towards this, we propose A Single-cell Guided Pipeline to Aid Repurposing of Drugs (ASGARD) that defines a...

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Autores principales: He, Bing, Xiao, Yao, Liang, Haodong, Huang, Qianhui, Du, Yuheng, Li, Yijun, Garmire, David, Sun, Duxin, Garmire, Lana X.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945835/
https://www.ncbi.nlm.nih.gov/pubmed/36813801
http://dx.doi.org/10.1038/s41467-023-36637-3
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author He, Bing
Xiao, Yao
Liang, Haodong
Huang, Qianhui
Du, Yuheng
Li, Yijun
Garmire, David
Sun, Duxin
Garmire, Lana X.
author_facet He, Bing
Xiao, Yao
Liang, Haodong
Huang, Qianhui
Du, Yuheng
Li, Yijun
Garmire, David
Sun, Duxin
Garmire, Lana X.
author_sort He, Bing
collection PubMed
description Single-cell RNA sequencing technology has enabled in-depth analysis of intercellular heterogeneity in various diseases. However, its full potential for precision medicine has yet to be reached. Towards this, we propose A Single-cell Guided Pipeline to Aid Repurposing of Drugs (ASGARD) that defines a drug score to recommend drugs by considering all cell clusters to address the intercellular heterogeneity within each patient. ASGARD shows significantly better average accuracy on single-drug therapy compared to two bulk-cell-based drug repurposing methods. We also demonstrated that it performs considerably better than other cell cluster-level predicting methods. In addition, we validate ASGARD using the drug response prediction method TRANSACT with Triple-Negative-Breast-Cancer patient samples. We find that many top-ranked drugs are either approved by the Food and Drug Administration or in clinical trials treating corresponding diseases. In conclusion, ASGARD is a promising drug repurposing recommendation tool guided by single-cell RNA-seq for personalized medicine. ASGARD is free for educational use at https://github.com/lanagarmire/ASGARD.
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spelling pubmed-99458352023-02-23 ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs He, Bing Xiao, Yao Liang, Haodong Huang, Qianhui Du, Yuheng Li, Yijun Garmire, David Sun, Duxin Garmire, Lana X. Nat Commun Article Single-cell RNA sequencing technology has enabled in-depth analysis of intercellular heterogeneity in various diseases. However, its full potential for precision medicine has yet to be reached. Towards this, we propose A Single-cell Guided Pipeline to Aid Repurposing of Drugs (ASGARD) that defines a drug score to recommend drugs by considering all cell clusters to address the intercellular heterogeneity within each patient. ASGARD shows significantly better average accuracy on single-drug therapy compared to two bulk-cell-based drug repurposing methods. We also demonstrated that it performs considerably better than other cell cluster-level predicting methods. In addition, we validate ASGARD using the drug response prediction method TRANSACT with Triple-Negative-Breast-Cancer patient samples. We find that many top-ranked drugs are either approved by the Food and Drug Administration or in clinical trials treating corresponding diseases. In conclusion, ASGARD is a promising drug repurposing recommendation tool guided by single-cell RNA-seq for personalized medicine. ASGARD is free for educational use at https://github.com/lanagarmire/ASGARD. Nature Publishing Group UK 2023-02-22 /pmc/articles/PMC9945835/ /pubmed/36813801 http://dx.doi.org/10.1038/s41467-023-36637-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
He, Bing
Xiao, Yao
Liang, Haodong
Huang, Qianhui
Du, Yuheng
Li, Yijun
Garmire, David
Sun, Duxin
Garmire, Lana X.
ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs
title ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs
title_full ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs
title_fullStr ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs
title_full_unstemmed ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs
title_short ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs
title_sort asgard is a single-cell guided pipeline to aid repurposing of drugs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945835/
https://www.ncbi.nlm.nih.gov/pubmed/36813801
http://dx.doi.org/10.1038/s41467-023-36637-3
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