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

• Published in: Nature communications Vol. 14; no. 1; pp. 993 - 14
• Main Authors: He, Bing, Xiao, Yao, Liang, Haodong, Huang, Qianhui, Du, Yuheng, Li, Yijun, Garmire, David, Sun, Duxin, Garmire, Lana X.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.02.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 49; 631/114; 631/154; 639/705/1042; 692/308/153; 692/308/575; Breast cancer; Chemotherapy; Clinical trials; Clusters; Drug Repositioning; Drug therapy; Drugs; Gene sequencing; Heterogeneity; Humanities and Social Sciences; Humans; multidisciplinary; Patients; Pharmaceutical Preparations; Precision Medicine; Predictions; Recommender systems; Ribonucleic acid; RNA; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-36637-3

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 . The full potential of single-cell RNA-sequencing applied to precision medicine has yet to be reached. Here, we propose a drug recommendation system ASGARD, which predicts drugs by considering cell clusters to address the intercellular heterogeneity within each patient.