Ratio of execution time for the GSVA, ssGSEA, VAM, and PLAGE methods to the execution time for RESET on simulated scRNA-seq data, the PBMC scRNA-seq data set for the MSigDB C2.CP.BIOCARTA collection, the cord blood scRNA-seq data set for the MSigDB C2.CP.BIOCARTA collection, the mouse brain scRNA-seq data set for the MSigDB C5.BP collection, and the Mouse Cell Atlas for a single synthetic gene set.

For the real scRNA-seq data, RESET was executed using the parameters specified in the Methods section in S1 Text. For the simulated data, execution times are relative to the fully randomized version (i.e., “RESET.ran”) as detailed in the Methods section in S1 Text.