ASGARD – 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, researchers from the University of Michigan Medical School have developed 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. The researchers also demonstrated that it performs considerably better than other cell cluster-level predicting methods. In addition, they validate ASGARD using the drug response prediction method TRANSACT with Triple-Negative-Breast-Cancer patient samples. They found 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.

The workflow of the ASGARD drug repurposing pipeline

Diseased and normal cells are paired according to “anchor” genes that are expressed consistently between the two types of cells. The differentially expressed (DE) genes are identified between diseased and normal cells, either within a cluster or within a cell type. Using the consistent DE genes as the input, potential drugs that significantly reverse the pattern of DE genes are identified, using the Kolmogorov–Smirnov (K-S) test with Benjamini–Hochberg (BH) false discovery rate (FDR) adjustment. Next ASGARD estimates and ranks the drug scores for single drugs, by targeting specific cell cluster(s) or all cell clusters.

Availability – ASGARD is free for educational use at https://github.com/lanagarmire/ASGARD