scGREAT: Graph-based regulatory element analysis tool for single-cell multi-omics data

Motivation With the development in single-cell multi-omics sequencing technology and data integration algorithms, we have entered the single-cell multi-omics era. Current multi-omics analysis algorithms failed to systematically dissect the heterogeneity within the datasets when inferring cis-regulatory events. Thus, there is a need for cis-regulatory element inferring algorithms that considers the cellular heterogeneity. Results Here, we propose scGREAT, a single-cell multi-omics regulatory state analysis Python package with a rapid graph-based correlation measurement L . The graph-based correlation method assigns each cell a local L index, pinpointing specific cell groups of certain regulatory states. Such single-cell resolved regulatory state information enables the heterogeneity analysis equipped in the package. Applying scGREAT to the 10X Multiome PBMC dataset, we demonstrated how it could help subcluster cell types, infer regulation-based pseudo-time trajectory, discover feature modules, and find cluster-specific regulatory gene-peak pairs. Besides, we showed that global L index, which is the average of all local L values, is a better replacement for Pearson’s r in ruling out confounding regulatory relationships that are not of research interests. Availability https://github.com/ChaozhongLiu/scGREAT