Fig. 4: Splicing and chromatin patterns diverge in primate evolution.
a, Downsampling experiment. Distribution of the percentage of peaks that are significantly different between humans and macaques in the vicinity of genes targeted for splicing analysis per cell type (n = 20). b, Downsampling experiment for subtypes with the same method described in a. c, Two peaks within TRRAP. The left peak is specific to human astrocytes but is absent in macaque astrocytes, and the right peak shows increased chromatin accessibility in human inhibitory neurons. H, human; M, macaque. d, A peak in CEP250 specific to human L5 IT_RORB cells but absent in macaque L5 IT_RORB cells. e, Correlation between ΔΨ values (neurons versus glia) of tested exons targeted by both exome probes and exon–exon junction probes indicated by regression using a linear model; shading indicates the 95% confidence interval (n = 414). Shading indicates peaks of interest. f, Downsampling experiment. Distribution of the percentage of exons showing significant differences between humans and macaques per cell type (Methods; n = 100). g, Cell-type-resolved isoform expression for NUBP2 plotted, with the top three tracks showing excitatory neurons, inhibitory neurons and astrocytes. h, Downsampling experiment for subtypes with the same method described in f (n = 100). i, Number of genes with one or more and two or more cell states detected in both species. Only genes with testable exons were considered. j, Volcano plot of state-specific exons across cell types in humans and macaques. Only exons with ten or more reads in two or more states were tested (n = 238 and 116 for human and macaque, respectively). Exons with a P value of ≤0.05 and | LOR | of >1 are labeled in color, and the others are in gray. A one-sided χ2 test followed by a Benjamini–Yekutieli multiple testing correction was applied to evaluate the significance of splicing–cell state association. k, Distribution of the maximum normalized-state ΔΨ per exon; normalized-state ΔΨ = state ΔΨ /overall ΔΨ. l, Pie chart showing the maximum normalized-state ΔΨ per exon split by value into three groups: <0.9, between 0.9 and 1 or ≥1. Each box plot shows the median (middle line), IQR (box) and adjacent values (whiskers extending to 1.5× the IQR). Dots represent outliers. A two-sided Wilcoxon rank-sum test was applied to all the comparisons shown in a, b, f and h. FDR correction was applied to multiple comparisons, and corrected P values (<0.05) are presented.
