Intercellular heterogeneity is a major obstacle to successful precision medicine. Single-cell RNA sequencing (scRNA-seq) technology has enabled in-depth analysis of intercellular heterogeneity in various diseases. However, its full potentials for precision medicine are yet to be reached. Towards this, we propose A Single-cell Guided pipeline to Aid Repurposing of Drugs (ASGARD). To precisely address the intercellular heterogeneity within each patient, ASGARD defines a novel drug score predicting drugs for multiple cell clusters. We tested ASGARD on three independent datasets, including advanced metastatic breast cancer, acute lymphoblastic leukemia, and coronavirus disease 2019 (COVID-19). On single-drug therapy, ASGARD shows significantly better average accuracy (AUC=0.95) compared to two other single-cell pipelines (AUC 0.69 and 0.57) and two other bulk-cell-based drug repurposing methods (AUC 0.80 and 0.75). The top-ranked drugs, such as fulvestrant and neratinib for breast cancer, tretinoin and vorinostat for leukemia, and enalapril for severe COVID19, are either approved by FDA or in clinical trials treating corresponding diseases. In conclusion, ASGARD is a promising pipeline guided by single-cell RNA-seq data, for repurposing drugs towards precision medicine. ASGARD is free for academic use at https://github.com/lanagarmire/ASGARD.
ASGARD: A Single-cell Guided pipeline to Aid Repurposing of Drugs (preprint)/ en