Single-nucleus profiling of postmortem diffuse midline gliomas identifies mitochondrial biogenesis as a resistance mechanism to imipridone therapy.
The 2 matches · 1 of them tie a paragraph to a whole file, not to given lines: a weak match, whose lines are not tinted
- [1] § Methods › Cell-Cell Communication Analysis ↔ 05_snRNA_cellchat.R, lines 182–253 · score 0.79 · groupSize, netVisual_aggregate, cell communication, Circle, vertex, CellChat
- [2] § Methods › SnATAC-Seq Data Processing and Analysis ↔ 07_snATAC_hclust_TF.R, the whole file · a weak match · score 0.55 · snapATAC, TF, barcodes, cut, Seurat, seq
Paper
Loaded from Europe PMC by your browser, not stored by OSCR: doi.org · Europe PMC
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The authors' code
R · 258 lines · 13 KB · MIT · 1 match
- library(Seurat)
- library(dplyr)
- library(ggplot2)
- library(patchwork)
- library(CellChat)
- library(ggalluvial)
- library(ComplexHeatmap)
- library(NMF)
- library(circlize)
- options(stringsAsFactors = FALSE)
- options(future.globals.maxSize= 891289600)
- setwd("/mnt/alamo01/users/gbb/NDMG_snRNA/seurat/Myeloid/ELSA_out/")
- MM <- read.table("Myeloid_scale.data_top100")
- Microglia <- subset(MM, subset = MM$V4=="Microglia")
- Macrophage <- subset(MM, subset = MM$V4=="Macrophage")
- snRNA <- readRDS("../../snRNA_All.rds")
- for (i in 1:length([email hidden]$orig.ident)){
- if(names([email hidden][i]) %in% Microglia[,1])
- {[email hidden]$cellType[i] = "Microglia"}
- else if(names([email hidden][i]) %in% Macrophage[,1])
- {[email hidden]$cellType[i] = "Macrophage"}
- }
- ################################# Location ###############
- setwd("/mnt/alamo01/users/gbb/NDMG_snRNA/cellchat/")
- snRNA_OP <- snRNA[,snRNA$treatement == "ONC201" & snRNA$location == "Pons"]
- snRNA_OT <- snRNA[,snRNA$treatement == "ONC201" & snRNA$location == "Thalamus"]
- snRNA_SP <- snRNA[,snRNA$treatement == "Standard" & snRNA$location == "Pons"]
- snRNA_ST <- snRNA[,snRNA$treatement == "Standard" & snRNA$location == "Thalamus"]
- # snRNA_UP <- snRNA[,snRNA$treatement == "Untreated" & snRNA$location == "Pons"]
- # snRNA_UT <- snRNA[,snRNA$treatement == "Untreated" & snRNA$location == "Thalamus"]
- rm(snRNA)
- gc()
- #
- cellchat <- createCellChat(object = snRNA_OP, group.by = "cellType", assay = "RNA")
- # cellchat <- createCellChat(object = snRNA_OT, group.by = "cellType", assay = "RNA")
- # cellchat <- createCellChat(object = snRNA_SP, group.by = "cellType", assay = "RNA")
- # cellchat <- createCellChat(object = snRNA_ST, group.by = "cellType", assay = "RNA")
- CellChatDB <- CellChatDB.human
- CellChatDB.use <- subsetDB(CellChatDB, search = "Secreted Signaling") # use Secreted Signaling
- cellchat@DB <- CellChatDB.use
- cellchat <- subsetData(cellchat)
- future::plan("multisession", workers = 15)
- cellchat <- identifyOverExpressedGenes(cellchat)
- cellchat <- identifyOverExpressedInteractions(cellchat)
- cellchat <- projectData(cellchat, PPI.human)
- cellchat <- computeCommunProb(cellchat, raw.use = FALSE)
- cellchat <- computeCommunProbPathway(cellchat)
- cellchat <- aggregateNet(cellchat)
- cellchat <- netAnalysis_computeCentrality(cellchat, slot.name = "netP")
- cellchat@netP$pathways
- saveRDS(cellchat, file = "snRNA_ONC201_Pons_CellChat.rds")
- # saveRDS(cellchat, file = "snRNA_ONC201_Thalamus_CellChat.rds")
- # saveRDS(cellchat, file = "snRNA_Standard_Pons_CellChat.rds")
- # saveRDS(cellchat, file = "snRNA_Standard_Thalamus_CellChat.rds")
- setwd("/mnt/alamo01/users/gbb/NDMG_snRNA/cellchat/location/")
- #################################Treatment ###############
- setwd("/mnt/alamo01/users/gbb/NDMG_snRNA/cellchat/")
- snRNA_O <- snRNA[,snRNA$treatement == "ONC201"]
- snRNA_S <- snRNA[,snRNA$treatement == "Standard"]
- rm(snRNA)
- gc()
- cellchat <- createCellChat(object = snRNA_O, group.by = "cellType", assay = "RNA")
- # cellchat <- createCellChat(object = snRNA_S, group.by = "cellType", assay = "RNA")
- CellChatDB <- CellChatDB.human
- CellChatDB.use <- subsetDB(CellChatDB, search = "Secreted Signaling") # use Secreted Signaling
- cellchat@DB <- CellChatDB.use
- cellchat <- subsetData(cellchat)
- future::plan("multisession", workers = 4)
- cellchat <- identifyOverExpressedGenes(cellchat)
- cellchat <- identifyOverExpressedInteractions(cellchat)
- cellchat <- projectData(cellchat, PPI.human)
- cellchat <- computeCommunProb(cellchat, raw.use = FALSE)
- cellchat <- computeCommunProbPathway(cellchat)
- cellchat <- aggregateNet(cellchat)
- cellchat <- netAnalysis_computeCentrality(cellchat, slot.name = "netP")
- cellchat@netP$pathways
- saveRDS(cellchat, file = "snRNA_ONC201_CellChat.rds")
- # saveRDS(cellchat, file = "snRNA_Untreated_CellChat.rds")
- # saveRDS(cellchat, file = "snRNA_Standard_CellChat.rds")
- }
- ############################ Compare
- ##################### ONC201_VS_Standard ################################
- cellchat.ONC201 <- readRDS("../snRNA_ONC201_CellChat.rds")
- cellchat.Standard <- readRDS("../snRNA_Standard_CellChat.rds")
- group.new = levels(cellchat.Standard@idents)
- cellchat.ONC201 <- liftCellChat(cellchat.ONC201, group.new)
- object.list <- list(ONC201 = cellchat.ONC201, Standard = cellchat.Standard)
- cellchat <- mergeCellChat(object.list, add.names = names(object.list), cell.prefix = TRUE)
- cellchat
- # Part I: Compare the total number of interactions and interaction strength
- pdf("ONC201_Standard_1.pdf")
- gg1 <- compareInteractions(cellchat, show.legend = F, group = c(1,2))
- gg2 <- compareInteractions(cellchat, show.legend = F, group = c(1,2), measure = "weight")
- gg1 + gg2
- #
- netVisual_diffInteraction(cellchat, weight.scale = T)
- netVisual_diffInteraction(cellchat, weight.scale = T, measure = "weight")
- #
- netVisual_heatmap(cellchat)
- netVisual_heatmap(cellchat, measure = "weight")
- # Compare the major sources and targets in 2D space
- num.link <- sapply(object.list, function(x) {rowSums(x@net$count) + colSums(x@net$count)-diag(x@net$count)})
- weight.MinMax <- c(min(num.link), max(num.link)) # control the dot size in the different datasets
- gg <- list()
- for (i in 1:length(object.list)) {
- gg[[i]] <- netAnalysis_signalingRole_scatter(object.list[[i]], title = names(object.list)[i],
- weight.MinMax = weight.MinMax)
- }
- patchwork::wrap_plots(plots = gg)
- # Subset T-cell and Tumor
- netAnalysis_signalingChanges_scatter(cellchat, idents.use = "Tumor")
- netAnalysis_signalingChanges_scatter(cellchat, idents.use = "T-cells") #, signaling.exclude = c("MIF"))
- netAnalysis_signalingChanges_scatter(cellchat, idents.use = "M0")
- netAnalysis_signalingChanges_scatter(cellchat, idents.use = "M1")
- netAnalysis_signalingChanges_scatter(cellchat, idents.use = "M2")
- netAnalysis_signalingChanges_scatter(cellchat, idents.use = "Neuron")
- netAnalysis_signalingChanges_scatter(cellchat, idents.use = "Astrocytes")
- netAnalysis_signalingChanges_scatter(cellchat, idents.use = "Oligodendrocytes")
- netAnalysis_signalingChanges_scatter(cellchat, idents.use = "Endothelial-cells")
- # Identify and visualize the conserved and context-specific signaling pathways
- gg1 <- rankNet(cellchat, mode = "comparison", stacked = T, do.stat = TRUE, font.size = 6)
- gg2 <- rankNet(cellchat, mode = "comparison", stacked = F, do.stat = TRUE, font.size = 6)
- gg1 + gg2
- # Outgoing
- i = 1
- pathway.union <- union(object.list[[i]]@netP$pathways, object.list[[i+1]]@netP$pathways)
- ht1 = netAnalysis_signalingRole_heatmap(object.list[[i]], pattern = "outgoing", signaling = pathway.union,
- title = names(object.list)[i], width = 5, height = 6,
- color.heatmap = "OrRd", font.size = 4)
- ht2 = netAnalysis_signalingRole_heatmap(object.list[[i+1]], pattern = "outgoing", signaling = pathway.union,
- title = names(object.list)[i+1], width = 5, height = 6,
- color.heatmap = "OrRd", font.size = 4)
- draw(ht1 + ht2, ht_gap = unit(0.5, "cm"))
- # Incoming
- ht1 = netAnalysis_signalingRole_heatmap(object.list[[i]], pattern = "incoming", signaling = pathway.union,
- title = names(object.list)[i], width = 5, height = 6,
- color.heatmap = "OrRd", font.size = 4)
- ht2 = netAnalysis_signalingRole_heatmap(object.list[[i+1]], pattern = "incoming", signaling = pathway.union,
- title = names(object.list)[i+1], width = 5, height = 6,
- color.heatmap = "OrRd", font.size = 4)
- draw(ht1 + ht2, ht_gap = unit(0.5, "cm"))
- # Overall
- ht1 = netAnalysis_signalingRole_heatmap(object.list[[i]], pattern = "all", signaling = pathway.union,
- title = names(object.list)[i], width = 5, height = 6,
- color.heatmap = "OrRd", font.size = 4)
- ht2 = netAnalysis_signalingRole_heatmap(object.list[[i+1]], pattern = "all", signaling = pathway.union,
- title = names(object.list)[i+1], width = 5, height = 6,
- color.heatmap = "OrRd", font.size = 4)
- draw(ht1 + ht2, ht_gap = unit(0.5, "cm"))
- dev.off()
- pdf("ONC201_Standard_2.pdf")
- for(i in 1:9){
- p <- netVisual_bubble(cellchat, sources.use = i, targets.use = c(1:9), comparison = c(1, 2),
- angle.x = 45, font.size = 4)
- plot(p)
- }
- #
- for(i in 1:9){
- p <- netVisual_bubble(cellchat, sources.use = i, targets.use = c(1:9), comparison = c(1, 2),
- max.dataset = 1, title.name = "Increased signaling in ONC201", angle.x = 45,
- remove.isolate = F, font.size = 4)
- plot(p)
- p <- netVisual_bubble(cellchat, sources.use = i, targets.use = c(1:9), comparison = c(1, 2),
- max.dataset = 2, title.name = "Decreased signaling in ONC201", angle.x = 45,
- remove.isolate = F, font.size = 4)
- plot(p)
- }
- # dysfunctional signaling by using DEGs
- pos.dataset = "ONC201"
- features.name = pos.dataset
- cellchat <- identifyOverExpressedGenes(cellchat, group.dataset = "datasets", pos.dataset = pos.dataset,
- features.name = features.name, only.pos = FALSE, thresh.pc = 0.1,
- thresh.fc = 0.1, thresh.p = 1)
- net <- netMappingDEG(cellchat, features.name = features.name)
- net.up <- subsetCommunication(cellchat, net = net, datasets = "ONC201",ligand.logFC = 0.2, receptor.logFC = 0.2) #???
- net.down <- subsetCommunication(cellchat, net = net, datasets = "Standard",ligand.logFC = -0.1, receptor.logFC = -0.1) #???
- gene.up <- extractGeneSubsetFromPair(net.up, cellchat)
- gene.down <- extractGeneSubsetFromPair(net.down, cellchat)
- pairLR.use.up = net.up[, "interaction_name", drop = F]
- pairLR.use.down = net.down[, "interaction_name", drop = F]
- for(i in c(1:3,6,7,9)){
- gg1 <- netVisual_bubble(cellchat, pairLR.use = pairLR.use.up, sources.use = i, targets.use = c(1:9),
- comparison = c(1, 2), angle.x = 45, remove.isolate = T,
- title.name = paste0("Up-regulated signaling in ", names(object.list)[1]))
- plot(gg1)
- gg2 <- netVisual_bubble(cellchat, pairLR.use = pairLR.use.down, sources.use = i, targets.use = c(1:9),
- comparison = c(1, 2), angle.x = 45, remove.isolate = T,
- title.name = paste0("Down-regulated signaling in ", names(object.list)[1]))
- plot(gg2)
- }
- for(i in c(1,2,6,9)){
- netVisual_chord_gene(object.list[[1]], sources.use = i, targets.use = c(1:9), slot.name = 'net',
- net = net.up, lab.cex = 0.8, small.gap = 3.5,
- title.name = paste0("Up-regulated signaling in ", names(object.list)[1]))
- } #
- for(i in c(1,2,4:9)){
- netVisual_chord_gene(object.list[[2]], sources.use = i, targets.use = c(1:9), slot.name = 'net',
- net = net.down, lab.cex = 0.8, small.gap = 3.5,
- title.name = paste0("Down-regulated signaling in ", names(object.list)[1]))
- } #
- dev.off()
- # Part IV: Visually compare cell-cell communication using Hierarchy plot, Circle plot or Chord diagram
- pathways_ONC201 <- object.list[[1]]@netP$pathways
- pathways_Standard <- object.list[[2]]@netP$pathways
- pathways.show <- intersect(pathways_Standard, pathways_ONC201)
- groupSize.ONC201 <- as.numeric(table(cellchat.ONC201@idents))
- groupSize.Standard <- as.numeric(table(cellchat.Standard@idents))
- # Circle
- pdf("ONC201_Standard_3.pdf")
- par(mfrow = c(1,2), xpd=TRUE)
- for(i in 1:length(pathways.show)){
- weight.max <- getMaxWeight(object.list, slot.name = c("netP"), attribute = pathways.show[i])
- netVisual_aggregate(object.list[[1]], signaling = pathways.show[i], layout = "circle", edge.weight.max = weight.max[1],
- vertex.weight = groupSize.ONC201, signaling.name = paste(pathways.show[i], names(object.list)[1]))
- netVisual_aggregate(object.list[[2]], signaling = pathways.show[i], layout = "circle", edge.weight.max = weight.max[1],
- vertex.weight = groupSize.Standard, signaling.name = paste(pathways.show[i], names(object.list)[2]))
- }
- # Heatmap
- par(mfrow = c(1,2), xpd=TRUE)
- for(i in 1:length(pathways.show)){
- ht <- list()
- ht[[1]] <- netVisual_heatmap(object.list[[1]], signaling = pathways.show[i], color.heatmap = "Reds",
- title.name = paste(pathways.show[i], "signaling ",names(object.list)[1]))
- ht[[2]] <- netVisual_heatmap(object.list[[2]], signaling = pathways.show[i], color.heatmap = "Reds",
- title.name = paste(pathways.show[i], "signaling ",names(object.list)[2]))
- ComplexHeatmap::draw(ht[[1]] + ht[[2]], ht_gap = unit(0.5, "cm"))
- }
- # Chord diagram
- par(mfrow = c(2,2), xpd=TRUE)
- for(i in 1:length(pathways.show)){
- netVisual_aggregate(object.list[[1]], signaling = pathways.show[i], layout = "chord",
- signaling.name = paste(pathways.show[i], names(object.list)[1]))
- netVisual_aggregate(object.list[[2]], signaling = pathways.show[i], layout = "chord",
- signaling.name = paste(pathways.show[i], names(object.list)[2]))
- }
- dev.off()
05_snRNA_cellchat.R at commit 6d5efbb, under MIT · at the source
Overview
- Department of Neurological Surgery, University of California, San Francisco, California, USA
- Center for Cancer and Immunology Research, Children’s National Hospital, Washington, District of Columbia, USA
- State Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China
- Children’s Research Center, University Children’s Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Neurology, University of California, San Francisco, California, USA
Abstract
Background: Imipridone ONC201 is the first FDA-approved therapy for H3K27-altered diffuse midline glioma; however, clinical responses remain limited. Defining tumor-intrinsic determinants and microenvironmental, extrinsic factors that shape sensitivity or resistance to imipridones will identify actionable therapeutic opportunities and inform improved clinical strategies.
Methods: To identify mechanisms of imipridone resistance, we obtained postmortem brain tissue from DMG patients who had received imipridones and/
Results: We established a single-cell RNA/
Conclusions: These studies implicate mitochondrial biogenesis as a biomarker of imipridone resistance and a focus for the development of combinatorial strategies to provide effective therapeutic options for a challenging pediatric brain tumor.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
Its files are read in the Code ↔ Paper reader above, with 2 matches between paragraphs and lines of code.
CancerGenomicsLab/DMG_ONC201
6d5efbb554bb8428b07628dd5bd5cdd870ef23d6, 20 August 2025Availability: 1 check, the latest on 26 September 2026: the link answers
- 26 September 2026: the link answers
9 files
- 01_snRNA_preprocessing_c
ellAnno.R , R, 920 lines - 02_snRNA_preprocessing_i
nferCNV.R , R, 456 lines - 03_snRNA_integration.py, Python, 65 lines
- 04_snRNA_hcluster_PE&
MES.R , R, 152 lines - 05_snRNA_cellchat.R, R, 258 lines, 1 match
- 06_snATAC_integration.R, R, 249 lines
- 07_snATAC_hclust_TF.R, R, 86 lines, 1 match
- LICENSE, License, 21 lines
- README.md, Text, 37 lines
The paper's code and data availability statement is in the Data section.
Tracing map
Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.
What the map holds:
- 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
- 7 scripts, each with its path and the digest of its content;
- 2 matches between paragraphs of the paper and lines of the code (method lexical-v1);
- neither the text of the paper nor the code itself.
Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.
Data
No dataset and no data link were found in the paper.
Data and Code Availability
The study data are available and can be visualized on the UCSC Cell browser (https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 16 keywords, 12 MeSH terms, 7 funders, 45 references.
Cite
This paper
Okada, M., Subramaniam, B., Geng, B., Jung, J., Yu, B., Lin, F., Fu, Y., Wang, Y., Yu, W., Laternser, S., Gupta, N., Müller, S., Wang, L., Diaz, A., & Nazarian, J. (2026). Single-nucleus profiling of postmortem diffuse midline gliomas identifies mitochondrial biogenesis as a resistance mechanism to imipridone therapy. Neuro-oncology, 28(9), 2248-2262. https://
BibTeX
@article{okada2026single
author = {Okada, Masahiro and Subramaniam, Bavani and Geng, Baobao and Jung, Jangham and Yu, Bohyeon and Lin, Felicia and Fu, Yu and Wang, Yishu and Yu, Weiqiang and Laternser, Sandra and Gupta, Nalin and Müller, Sabine and Wang, Lin and Diaz, Aaron and Nazarian, Javad},
title = {{Single-nucleus profiling of postmortem diffuse midline gliomas identifies mitochondrial biogenesis as a resistance mechanism to imipridone therapy}},
journal = {Neuro-oncology},
year = {2026},
month = sep,
volume = {28},
number = {9},
pages = {2248--2262},
publisher = {Oxford University Press},
issn = {1522-8517},
doi = {10.1093/
url = {https://
pmid = {42178382},
pmcid = {PMC13550678}
}
RIS
TY - JOUR
AU - Okada, Masahiro
AU - Subramaniam, Bavani
AU - Geng, Baobao
AU - Jung, Jangham
AU - Yu, Bohyeon
AU - Lin, Felicia
AU - Fu, Yu
AU - Wang, Yishu
AU - Yu, Weiqiang
AU - Laternser, Sandra
AU - Gupta, Nalin
AU - Müller, Sabine
AU - Wang, Lin
AU - Diaz, Aaron
AU - Nazarian, Javad
TI - Single-nucleus profiling of postmortem diffuse midline gliomas identifies mitochondrial biogenesis as a resistance mechanism to imipridone therapy
T2 - Neuro-oncology
J2 - Neuro Oncol
PY - 2026
DA - 2026/
VL - 28
IS - 9
SP - 2248
EP - 2262
SN - 1522-8517
PB - Oxford University Press
DO - 10.1093/
UR - https://
LA - en
ER -
CSL-JSON
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"container-title": "Neuro-oncology",
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FOS/ EGR3/ EGR1, Contributing to the Hyperexcitability of Excitatory Neurons in the Epileptic Temporal Cortex and Hippocampus. Journal: International journal of molecular sciencesIn common: UMAP, anndata, circlize, 9 other tools, genetics / omics
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