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. 2023 Feb 23;29(3):615–622. doi: 10.1038/s41591-022-02141-2

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© The Author(s) 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 5 — a, Modulation of top stemness-related pathways associated with cellular differentiation in the central nervous system upon 2-HG suppression. ‘DN’ indicates that genes in these pathways are downregulated in stem cells. Padj is P value adjusted for multiple comparisons as described in the Methods: if padj<0.05, the pathway is significantly associated with 2-HG suppression. b, Unsupervised clustering of 2-HG–associated genes involved in neuronal differentiation and stemness (N = 41). Box plot: horizontal lines denote median values, boxes denote 25th to 75th percentiles, whiskers go from the smallest to the largest values; two-sided P value generated with Student’s t test. c, Methodology for the determination of genes associated with 2-HG suppression. d, Volcano plot highlighting genes associated with 2-HG suppression. e, Venn diagram between genes associated with IDH mutations derived by comparing wild-type IDH and mIDH low-grade glioma in The Cancer Genome Atlas dataset and genes associated with 2-HG suppression as shown in Extended Data Fig. 5a. f, Plot of the 151 overlapping genes derived from Panel a. Note that the majority of genes that are downregulated in mIDH tumors (left bar) are upregulated upon 2-HG suppression and vice versa (right bar). 2-HG denotes D-2-hydroxyglutarate; FC, fold change; IDH1, isocitrate dehydrogenase; mIDH1, mutant isocitrate dehydrogenase; NES, normalized enrichment score; padj, adjusted P value pval, P value; RNAseq, RNA sequencing.