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

Bing He, Yao Xiao, Haodong Liang, Qianhui Huang, Yuheng Du, Yijun Li, David Garmire, Duxin Sun and Lana X. Garmire ()
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Bing He: University of Michigan
Yao Xiao: University of Michigan
Haodong Liang: University of Michigan
Qianhui Huang: University of Michigan
Yuheng Du: University of Michigan
Yijun Li: University of Michigan
David Garmire: University of Michigan
Duxin Sun: University of Michigan
Lana X. Garmire: University of Michigan

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract 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 .

Date: 2023
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DOI: 10.1038/s41467-023-36637-3

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