Fig. 5: Evolutionarily conserved transcript diversity in synaptic genes across the human prefrontal cortex.
From: Mapping isoforms and regulatory mechanisms from spatial transcriptomics data with SPLISOSM
a, Workflow overview. b, Relationship between total read coverage in TREND regions per spot (x axis) and number of significant SVP (top, HSIC-IR adjusted P < 0.01) or variably expressed (SVE, bottom, HSIC-GC adjusted P < 0.01) genes across datasets. Line and shading indicate fitted linear model and 95% confidence interval. c, P value correlation distributions between technical replicates (left), different sections from same donor (middle) and different donors (right). Genes are stratified by average TREND read counts per spot and group means are compared using the Kruskal–Wallis test. Boxplots show median (center line), interquartile range (box) and 1.5× interquartile range (whiskers). d, SVP genes ranked by recurrence (number of significant samples, x axis) and the minimal HSIC-IR P values across samples (y axis). Highlighted genes have mouse homologs that are also spatially variably spliced (HSIC-IR adjusted P < 0.01). e, Distributions of average conservation scores in TREND regions across gene categories: nonvariable controls (n = 12,107), human-specific SVENP (n = 8,044) or SVP (n = 1,319) and human-mouse shared SVENP (n = 4,022) or SVP (n = 401). Boxplots show median (center line), interquartile range (box) and 1.5× interquartile range (whiskers). Pairwise group means are compared using two-sided t-test. f, Pathway enrichment analysis comparing SVP (orange) versus SVENP (dark blue) genes conserved between human and mouse. g, RBP-SVP associations ranked by recurrence (x axis) and minimal GLMM P values across samples (y axis). Top potential regulators of SEPTIN8 are highlighted and colored by whether the association is conserved in mouse (P < 0.01 for both GLMM and HSIC-based DU tests). h, SEPTIN8 transcript structure and spatial log-normalized expression in mouse (top) and human (bottom, sample 151673). i, SEPTIN8-long and SEPTIN8-short protein variants with potentially different cellular functions. Panels a and i created using BioRender.com.
