Fig. 2: scMORE identifies cell type-specific eRegulons relevant to two hematological traits. | Nature Aging

Fig. 2: scMORE identifies cell type-specific eRegulons relevant to two hematological traits.

From: Integrating polygenic signals and single-cell multiomics identifies cell-type-specific regulomes critical for immune- and aging-related diseases

Fig. 2

a, Uniform Manifold Approximation and Projection (UMAP) plot showing the cellular composition of a ground-truth single-cell multiomic dataset (monocytes, n = 1,000 cells and CD8+ T cells, n = 1,000 cells). b, Scatter-plot of scMORE-identified eRegulons associated with the lymphocyte count trait in CD8+ T cells. Each dot represents an eRegulon, with the -log-transformed GRS P values (−log10(P)) shown on the y axis and the −log-transformed CTS P values (−log10(P)) shown on the x axis. Gray dots indicate nonsignificant eRegulons and red dots represent significant eRegulons. Significance was assessed by an MC permutation test (one-sided, upper tail; n = 1,000 iterations; no multiple correction). c, Scatter-plot of scMORE-identified eRegulons relevant to the lymphocyte count trait in monocytes. No significant eRegulons were identified. Significance was assessed by an MC permutation test (one-sided, upper tail; n = 1,000 iterations; no multiple correction). d, Illustration of the performance of scMORE in identifying lymphocyte count trait-relevant eRegulons. Four lymphocyte count trait-relevant eRegulons exhibited stronger regulon activity scores in CD8+ T cells compared to monocytes. e, Heatmap displaying the TRSs of four significant eRegulons for both lymphocyte count and lymphocyte percent traits across monocytes and CD8+ T cells. The heatmap was generated using the pheatmap R package based on TRSs. The color bar represents TRS magnitude. **Denotes PCTS < 0.05, PGRS < 0.05 and PTRS < 0.01; *Denotes PCTS < 0.05, PGRS < 0.05 and PTRS < 0.05. Significance was assessed by an MC permutation test (one-sided, upper tail; n = 1,000 iterations; no multiple correction). f, Two-sided Pearson correlation of TRSs between lymphocyte count and lymphocyte percent, stratified by CD8+ T cells and monocytes. g, Benchmarking analysis comparing the performance of scMORE’s cosine specificity method with the averaged gene expression method. The E-statistics for each trait was calculated using getEnergyScore() function in scMORE. Each dot in boxplot indicates a blood trait. The two-sided paired Student’s t-test was used to assess statistical significance (n = 10 blood traits). Boxplot shows the median (center line), interquartile range (IQR; box) and 1.5 × IQR bounds (whiskers). Minima and maxima are represented by the whiskers.

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