We ran a similar runtime benchmarking analysis to that described above for Signac, using ArchR v.1.0.1 (ref. 35). To create the Arrow files needed for an analysis in ArchR, we ran the createArrowFiles function providing each downsampled fragment file as input, with addGeneScoreMat = FALSE and addTileMat = FALSE to avoid running additional steps. For comparison with the FeatureMatrix function in Siganc (peak region quantification), we ran the addPeakMatrix function in ArchR. For comparison with the GeneActivity function in Signac, we ran the addGeneScoreMatrix function in ArchR. For comparison with Signac LSI (RunTFIDF and RunSVD functions), we ran the addIterativeLSI function in ArchR with sampleCellsPre = NULL.