TENET+: a tool for reconstructing gene networks by integrating single cell expression and chromatin accessibility data

Reconstruction of gene regulatory networks (GRNs) is a powerful approach to capture a prioritized gene set controlling cellular processes. In our previous study, we developed TENET a GRN reconstructor from single cell RNA sequencing (scRNAseq). TENET has a superior capability to identify key regulators compared with other algorithms. However, accurate inference of gene regulation is still challenging. Here, we suggest an integrative strategy called TENET+ by combining single cell transcriptome and chromatin accessibility data. By applying TENET+ to a paired scRNAseq and scATACseq dataset of human peripheral blood mononuclear cells, we found critical regulators and their epigenetic regulations for the differentiations of CD4 T cells, CD8 T cells, B cells and monocytes. Interestingly, TENET+ predicted LRRFIP1 and ZBTB16 as top regulators of CD4 and CD8 T cells which were not predicted in a motif-based tool SCENIC. In sum, TENET+ is a tool predicting epigenetic gene regulatory programs in unbiased way, suggesting that novel epigenetic regulations can be identified by TENET+.