Fig. 6: ST diversity in human glioma is shaped by microenvironment composition and immune infiltration.
From: Mapping isoforms and regulatory mechanisms from spatial transcriptomics data with SPLISOSM
a, Workflow overview. b, SVP genes ranked by recurrence and the minimal HSIC-IR P values across samples in ONT (left) and SR (right) cohorts. Orange indicates glioma-specific genes not variable (HSIC-IR adjusted P ≥ 0.05) in all healthy DLPFC samples. c, Distributions of recurrent and glioma-specific SVP genes. d, Pathway enrichment analysis comparing recurrent SVP (HSIC-IR adjusted P < 0.05 in ≥2 samples) genes versus recurrent SVENP (non-SVP and HSIC-GC adjusted P < 0.05 in ≥4 samples) genes. e, Spatial distribution of HLA-DRB1 isoforms in the ONT sample GBM1. f, B2M and CD74 isoform expression in GBM1, comparing tumor (n = 3,706) versus immune-infiltrated (n = 898) spots. Three novel CD74 intron-retention isoforms are pooled together for visualization. Boxplots show median (center line), interquartile range (box) and 1.5× interquartile range (whiskers). P values from two-sided t-test. g, TPM3 transcript structure, RNA-seq coverage, and spatial patterns in the SR sample ZH916bulk. Event counts were locally smoothed when computing ratios, same in l,m. h, Glioblastoma metaprogram distribution in regions with high or low TPM3-event 1 usage. P value from one-sided chi-square test. Right: log-normalized expression (logExpr) of selected markers: SNAP25 (neuron), ACTB (glial), IGKC (B cell), NDRG1 (hypoxia). AC, astrocyte-like; MES, mesenchymal-like; MES.Ast, astrocytic-like mesenchymal; MES.Hyp, MES-hypoxia; Vasc, endothelia cells and pericytes. i, FTH1 transcript structure in ONT sample DMG3 and its RNA-seq coverage in SR sample ZH8811Abulk. j, Hypoxia marker expression and association with FTH1-211 usage in DMG3. P value from one-sided chi-square test. k, Histology (left), metaprogram distribution (middle, P value from one-sided chi-square test) and hemoglobin expression (right) in spots with high (n = 438) or low (n = 1,945) FTH1-event 2 usage in ZH8811Abulk. Mac, macrophage/microglia; OPC, oligodendrocyte progenitor-like; NPC, neural progenitor-like. Boxplots show median (center line), interquartile range (box) and 1.5× interquartile range (whiskers), with P values from two-sided t-test. l, Spatial distribution of FTH1 isoforms in DMG3. m, Spatial distribution of FTH1 TREND usage in ZH8811Abulk. Panel a created using BioRender.com.
