Extended Data Fig. 8: Benchmark of SCENIC+ and other methods on the melanoma cell lines data set.

a. Boolean networks were generated from gene regulatory networks inferred from SCENIC+, CellOracle, FigR and GRaNIE. For SCENIC+ the top 10%, 25% and 50% of edges based on the triplet score were used. 500 cells were simulated using the boolODE method using a simulation time of 20 and the hill activation function. Simulated cells were co-embedded in PCA space with real cells after Harmony batch effect correction. b. Violin and jitter plot of the average distance of each simulated cell to its three nearest neighbors in the first 2 principal components of PCA space. Difference in mean is assessed using two-tailed Mann-Whitney U test and p values are adjusted using the Benjamini–Hochberg procedure. y axis is sorted by the median average distance. c. ChIP-seq enrichment of SOX10, MITF and TFAP2A in target regions of SOX10, MITF and TFAP2A and all combinations of two. Signal is scaled across all comparisons between 0 and 1. d. -log10 p value (t-test) and average log2 fold change of target genes of eRegulons after SOX10 knockdown in MM001. Color scale encodes log2 fold change of the expression of the TF corresponding to each eRegulon after SOX10 knockdown. e. Scatter and jitter plot showing enhancer activity as measured by the STARR-seq method¹⁸ in regions targeted by any of the regulons and regions targeted by None. f. Scatter plot comparing enhancer activity as measure by the STARR-seq method (y axis)¹⁸ to the minimum of the triplet score over all TFs targeting and genes targeted by the region (x axis). Labels of the regions are according to the labels in Mauduit et al.¹⁸. Difference in mean is assessed using two-tailed Mann-Whitney U test and p values are adjusted using the Benjamini–Hochberg procedure. x axis is sorted by the median average distance. g. Heat map showing whether a TF is found across different e(GRN) inference methods (present: green; absent: red). Only TFs found by SCENIC+ are shown.