Fig. 3: Cell type CREs identified with RENIN. | Nature Communications

Fig. 3: Cell type CREs identified with RENIN.

From: Predicting proximal tubule failed repair drivers through regularized regression analysis of single cell multiomic sequencing

Fig. 3

a ROC curve calculated for RENIN-predicted healthy-failed repair (FR) proximal tubule (PT) cis-regulatory elements (CREs) against RPTEC H3K4me3 peaks identified with CUT&RUN performed on n = 3 independent samples. FR CREs determined by predicted regulation of a marker gene of the KIM1+ cluster and healthy CREs determined by predicted regulation of a PCT and/or PST cluster marker gene. Source data are provided in the Source Data file. b ROC curve calculated for RENIN-predicted healthy-FR PT CREs against RPTEC H3K27ac peaks identified with CUT&RUN performed on n = 3 independent samples. Source data are provided in the Source Data file. c ROC curve calculated for LinkPeaks-predicted healthy-FR PT CREs against RPTEC H3K4me3 CUT&RUN peaks. Source data are provided in the Source Data file. d ROC curve calculated for LinkPeaks-predicted healthy-FR PT CREs against RPTEC H3K27ac CUT&RUN peaks. Source data are provided in the Source Data file. e ROC curve calculated for DIRECT-NET-predicted healthy-FR PT CREs against RPTEC H3K4me3 CUT&RUN peaks. Source data are provided in the Source Data file. f ROC curve calculated for DIRECT-NET-predicted healthy-FR PT CREs against RPTEC H3K27ac CUT&RUN peaks. Source data are provided in the Source Data file. g Area under curve (AUC) calculations for all tested methods against H3K27ac CUT&RUN peaks (left) and H3K4me3 CUT&RUN peaks (right). Each tested method’s quantitative metric was used. FigR CREs were scored by rObs, SCENIC+ CREs were scored by summed R2G_importance_x_abs_rho across all target genes, Cicero CREs were sorted by summed coaccessibility score, and scMEGA CREs were sorted by the TStat metric summed across all target genes. AUCs for H3K27ac peaks: RENIN (FR CRE: 0.694, Healthy CRE: 0.570), LinkPeaks (FR CRE: 0.435, Healthy CRE: 0.422), DIRECT-NET (FR CRE: 0.630, Healthy CRE: 0.621), FigR (FR CRE: 0.622, Healthy CRE: 0.552), SCENIC+ (FR CRE: 0.559, Healthy CRE: 0.450), Cicero (FR CRE: 0.536, Healthy CRE: 0.552), and scMEGA (H-FR trajectory CRE: 0.570). AUCs for H3K4me3 peaks: RENIN (FR CRE: 0.696, Healthy CRE: 0.607), LinkPeaks (FR CRE: 0.350, Healthy CRE: 0.388), DIRECT-NET (FR CRE: 0.649, Healthy CRE: 0.644), FigR (FR CRE: 0.637, Healthy CRE: 0.564), SCENIC+ (FR CRE: 0.489, Healthy CRE: 0.428), Cicero (FR CRE: 0.585, Healthy CRE: 0.587), and scMEGA (H-FR trajectory CRE: 0.513). Source data are provided in the Source data file. h Comparison of RENIN, LinkPeaks, and DIRECT-NET by enrichment of partitioned heritability of CKD in model-predicted healthy (PCT + PST) and FR (failed repair—KIM1 + PT) CREs. N = 7 biologically independent samples containing 50,768 cells were examined in a joint analysis. Error bars represent standard errors around estimates of enrichment by LDSC with a block jackknife over n = 200 equally sized blocks of adjacent SNPs. P values shown for two-tailed t-test of difference between enrichment means with degrees of freedom = 199. Source data are provided in the Source Data file.

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