Fig. 2: Altered gene programs following safusidenib treatment.
From: Perioperative IDH inhibition in treatment-naive IDH-mutant glioma: a pilot trial
a, UMAP plot depicting 158,487 nuclei identified in n = 9 matched samples using snRNA-seq from participants pre- and post-safusidenib. Top left: pre- and post-safusidenib conditions; top right: nonmalignant and malignant cells determined by Numbat; bottom: annotated UMAP clusters of glial tumor and normal cell states. b, Fraction of each cell state in pre- and post-safusidenib samples (n = 9 participants). Cell type legend as in a. c, Comparison of all tumor cells in matched pre- and post-safusidenib samples using GSEA. Each dot represents a gene set and the color indicates whether the gene set belongs to a glioma program; top enriched pathways are annotated. The x-axis shows the GSEA normalized enrichment score, and the y-axis shows the adjusted P value. The line depicts the significance threshold (adjusted P = 0.05). d, Dot plot depicting key semantic terms summarizing significant gene sets for each cell type population from GSEA. Each dot represents the proportion of significant pathways related to that term and is color coded to indicate the direction of enrichment—pre- or post-safusidenib. The accompanying bar plot illustrates the counts and enrichment direction of significant gene sets per semantic term for the tumor compartment. e, log(FC) in the AC-like program compared with log(FC) in the IFN program in AC-like tumor cells pre-safusidenib relative to post-safusidenib treatment (n = 9 participants, t-test). f, Representative immunohistochemistry staining of CD68 in the first surgery and biopsy, and the second surgery, from untreated patients (no treatment, surgery only) compared with participant O-01 pre- and post-safusidenib tissue. Quantification percentage CD68+ cells (no treatment, n = 6 matched samples; safusidenib, n = 10 matched samples). Mean ± s.e.m. (no treatment: 14.6 ± 3.1% at first surgery and biopsy, 30.3 ± 2.6% at surgery; safusidenib: 12.3 ± 3.5% at first surgery and biopsy, 21.6 ± 5.5% at surgery). Individual dots represent matched patient samples. Participant legend as in e. g, Example of vasculature in participant A-05 pre-safusidenib and post-safusidenib (n = 3 per condition). Single-cell spatial maps (Voronoi) of the expression of the CD69 transcript, cell state annotation and protein expression by immunofluorescence (CD31, CD68, mIDH and GFAP), with location in tissue (scale bars, 1 mm; annotation legend in a). Inset scale bars, 100 µm.
