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Spinal nociceptive denervation impedes subsequent chronic autonomic remodeling after myocardial infarction in male swine.

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  1. [1] § Methods › Plasma proteomics › Data analysis ↔ pathway_enrichment.R, lines 44–110 · score 0.74 · fold change, Gene Ontology, expressed proteins, GO, RITAN, log2

Paper

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The authors' code

R · 125 lines · 5.1 KB · MIT · 1 match

  1. ################################################################################
  2. ## Gene Ontology pathway enrichment of plasma differentially expressed proteins
  3. ##
  4. ## Companion code for:
  5. ## van Weperen et al. "Spinal nociceptive denervation impedes chronic autonomic
  6. ## remodeling after myocardial infarction"
  7. ##
  8. ## Description
  9. ## Performs over-representation (term enrichment) analysis of differentially
  10. ## expressed plasma proteins (DEPs) against the Gene Ontology (GO) database
  11. ## using RITAN, separately for up- and down-regulated proteins. For each set it
  12. ## reports, per GO term, the gene ratio (proteins in the DEP list mapping to the
  13. ## term / term set size), the protein count, and the enrichment p-value. The
  14. ## exported enrichment tables were used to generate the published figure panel
  15. ## in GraphPad Prism.
  16. ##
  17. ## Scope
  18. ## This script covers the DOWNSTREAM pathway enrichment only. Plasma sample
  19. ## preparation, LC-MS/MS acquisition, and DEP identification (DIA-NN,
  20. ## FragPipe-Analyst) were performed by the UCLA Proteome Research Center, which
  21. ## provided the DEP table (Data/dep.xlsx) used here as input. The final figure
  22. ## was produced in GraphPad Prism from the enrichment tables exported below.
  23. ## Raw and processed proteomics data are in ProteomeXchange/PRIDE under
  24. ## accession [TO BE ADDED], not in this repository.
  25. ##
  26. ## Input
  27. ## Data/dep.xlsx -- one row per protein, PRODUCED BY THE CORE FACILITY, with
  28. ## columns:
  29. ## Protein ID, Gene Name,
  30. ## X1_vs_X2_log2 fold change, X1_vs_X2_p.val, X1_vs_X2_p.adj,
  31. ## significant, X1_vs_X2_significant, imputed, num_NAs
  32. ## ("X1_vs_X2" denotes the contrast as exported by FragPipe-Analyst /
  33. ## DIA-NN label-free quantification; here cRTX+MI vs Vehicle+MI.)
  34. ##
  35. ## Output
  36. ## up_pathways.xlsx, down_pathways.xlsx -- full significant enrichment tables
  37. ## (subsequently plotted in Prism)
  38. ##
  39. ## Author: Jonathan D. Hoang
  40. ## License: MIT (see LICENSE)
  41. ################################################################################
  44. # ---- 1. Dependencies ---------------------------------------------------------
  45. # CRAN packages install via install.packages(); Bioconductor packages (RITAN,
  46. # RITANdata) install via BiocManager. BiocManager itself is bootstrapped if
  47. # absent.
  49. if (!requireNamespace("BiocManager", quietly = TRUE)) {
  50. install.packages("BiocManager")
  51. }
  53. cran_pkgs <- c("tidyverse", "readxl", "rstudioapi", "WriteXLS")
  54. bioc_pkgs <- c("RITAN", "RITANdata")
  56. for (pkg in cran_pkgs) {
  57. if (!requireNamespace(pkg, quietly = TRUE)) install.packages(pkg)
  58. }
  59. for (pkg in bioc_pkgs) {
  60. if (!requireNamespace(pkg, quietly = TRUE)) BiocManager::install(pkg, update = FALSE)
  61. }
  63. library(RITAN)
  64. library(RITANdata) # provides geneset_list (GO, etc.)
  65. library(tidyverse)
  66. library(readxl)
  69. # ---- 2. Parameters -----------------------------------------------------------
  70. # Edit these to re-run with different thresholds or input/output locations.
  72. dep_file <- file.path("Data", "dep.xlsx") # differentially expressed proteins
  73. logfc_thr <- 0.5 # |log2 fold change| cutoff for a DEP
  74. p_thr <- 0.05 # nominal p-value cutoff for a DEP and for enrichment
  75. resources <- "GO" # RITAN geneset resource(s); manuscript uses Gene Ontology
  77. # Resolve the working directory to this script's location (RStudio) so that the
  78. # relative paths above are stable regardless of where R was launched. Falls back
  79. # to the current working directory when run via Rscript / a non-RStudio session.
  80. if (rstudioapi::isAvailable()) {
  81. setwd(dirname(rstudioapi::getSourceEditorContext()$path))
  82. }
  85. # ---- 3. Load and split differentially expressed proteins ---------------------
  86. # DEPs are defined as proteins passing both the fold-change and p-value cutoffs.
  87. # They are split by the sign of the log2 fold change into up- and down-regulated
  88. # sets (relative to the cRTX+MI vs Vehicle+MI contrast). Gene symbols are upper-
  89. # cased to match RITAN's GO geneset identifiers.
  91. dep <- read_xlsx(dep_file)
  93. # Standardize the two columns used downstream to syntactic names.
  94. dep <- dep %>%
  95. rename(log2fc = `X1_vs_X2_log2 fold change`,
  96. pval = `X1_vs_X2_p.val`)
  98. is_dep <- abs(dep$log2fc) > logfc_thr & dep$pval < p_thr
  99. up_dep <- toupper(dep$`Gene Name`[is_dep & dep$log2fc > 0])
  100. down_dep <- toupper(dep$`Gene Name`[is_dep & dep$log2fc < 0])
  102. message(sprintf("Up-regulated DEPs: %d | Down-regulated DEPs: %d",
  103. length(up_dep), length(down_dep)))
  106. # ---- 4. Term enrichment (over-representation) against GO ----------------------
  107. # RITAN::term_enrichment tests each set against every term in `resources`.
  108. # GeneRatio = n (DEPs in term) / n.set (term size). Significant terms (p < p_thr)
  109. # are ordered by p-value and written out; these tables were imported into
  110. # GraphPad Prism to produce the published figure.
  112. enrich <- function(genes) {
  113. e <- term_enrichment(genes, resources = resources)
  114. e$GeneRatio <- e$n / e$n.set
  115. e <- e[e$p < p_thr, ]
  116. e[order(e$p, decreasing = FALSE), ]
  117. }
  119. e_up <- enrich(up_dep)
  120. e_down <- enrich(down_dep)
  122. WriteXLS::WriteXLS(e_up, "up_pathways.xlsx")
  123. WriteXLS::WriteXLS(e_down, "down_pathways.xlsx")
  125. message("Done. Wrote: up_pathways.xlsx, down_pathways.xlsx")

pathway_enrichment.R at commit 28a4fed, under MIT · at the source

Overview

Authors: Valerie Y. H. van Weperen1, Jonathan D. Hoang1,2, Neil R. Jani1, Shail Avasthi1, Christopher A. Chan1, Kuan Cao1, Zulfiqar A. Lokhandwala1, Maryam Emamimeybodi1, Karim Atmani1, Marmar Vaseghi1,2
ORCID iDs: Valerie Y. H. van Weperen, Jonathan D. Hoang, Shail Avasthi, Zulfiqar A. Lokhandwala, Maryam Emamimeybodi, Karim Atmani, Marmar Vaseghi
  1. UCLA Electrophysiology Programs, Division of Cardiology, Department of Medicine, University of California, Los Angeles (UCLA),Los Angeles, CA USA
  2. Molecular, Cellular, and Integrative Physiology Interdepartmental Programs, UCLA,Los Angeles, CA USA
Institutions: University of California, Los Angeles (United States)
Journal: Nature communications, volume 17, issue 1, article 8955
Dates: received 17 March 2025; accepted 10 July 2026; published online 22 July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-75759-2 · PMID 42637749 · PMCID PMC13503775 · OpenAlex W7170067692
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: pain (population)
Methods: Spectral & time-frequency, Statistics, Smoothing, state filtering, decompositions, Machine learning, Evoked potentials, Single-unit activity, calcium imaging
Keywords: Ventricular tachycardia, Cardiovascular diseases, Cardiology, Myocardial infarction
MeSH: Autonomic Nervous System*, Myocardial Infarction*, Nociceptors*, Spinal Cord*, Animals, Baroreflex, Diterpenes, Male, Swine, Vagus Nerve (* major topic)
Topic: Vagus Nerve Stimulation Research (Neurology, Neuroscience), according to OpenAlex
Funding: HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) (R01HL148190, R01HL70626)
Citations: not cited yet (Europe PMC); 152 references in the paper

Abstract

After chronic myocardial infarction (MI), pathological autonomic remodeling, including vagal dysfunction and sympathoexcitation, predisposes to ventricular arrhythmias (VT/VF). However, what underlies this functional and structural remodeling remains unknown. We hypothesized that spinal nociceptive afferent signaling initiates and perpetuates these pathological autonomic changes. We employed cervicothoracic epidural resiniferatoxin (RTX) to ablate spinal nociceptive neurons in male pigs before MI, and assessed autonomic and electrophysiological function four-to-six weeks post-infarction. Compared to vehicle-treated infarcted animals, epidural RTX attenuated the loss of vagal tone and baroreflex sensitivity, reduced spinal cord inflammation, glial activation, and circulating stress and inflammatory markers, and stabilized electrophysiological parameters, lowering VT/VF inducibility. In a separate cohort, acute C7–T1 nociceptive afferent ablation after chronic MI acutely restored vagal function and decreased VT/VF inducibility. This study demonstrates that cervicothoracic spinal nociceptive afferents significantly contribute to MI-induced autonomic remodeling and VT/VF, providing novel insight into the mechanisms underlying sympathovagal imbalance after MI.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repositories

Its files are read in the Code ↔ Paper reader above, with 1 match between paragraphs and lines of code.

jdthoang/vanWeperenV_2026_EpiduralRTX

License: MIT
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: 28a4feded9dff6ea6cedb4ea1d6c5f4143fc1933, 16 June 2026
Languages: R (1)
Size: 4 files, 1 script
Software Heritage: not archived
Found in: “Code availability”
Holds: README, license file
Not found: CITATION.cff, environment file, tests, continuous integration, documentation
Tools: tidyverse (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
3 files
At the source: github.com/jdthoang/vanWeperenV_2026_EpiduralRTX/

Zenodo 20711756

License: MIT
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Size: 1 file
Software Heritage: not checked
Found in: “Code availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: tidyverse (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers (HTTP 200)
  • 27 September 2026: the link answers (HTTP 200)
3 files
At the source:

Code availability

Custom code used to process the extracellular neural recordings and to analyze the plasma proteomic data (differential expression, and pathway enrichment) is available at GitHub (https://github.com/jdthoang/vanWeperenV_2026_EpiduralRTX/) and archived at Zenodo (10.5281/zenodo.20711756). Pathway analysis was performed with RITAN (v3.20) in R (v4.4.2). Customized software, iScaldyn (University of Utah), was used to compute activation-recovery intervals and is freely available upon request from Robert L. Lux. Image quantification was performed in ImageJ (NIH, v1.54). No other custom code was generated in this study.

Reproduced under the paper's license (CC BY), from the paper cited above.

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:

  • 2 repositories of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 2 scripts, each with its path and the digest of its content;
  • 1 match 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 availability

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository under accession code MV000099727 (https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=9d63769e90804f8091546cfca56052cb). Source data underlying all figures, including individual data points, are provided with this paper in the Source Data file and Supplementary data 1 and 2. Raw acquisition files (electrophysiological recordings, neural recordings, and confocal microscopy images) are large and are available from the corresponding author on request, owing to file-size and format constraints; their summary measurements are fully reported in the Source Data file. Source data are provided with this paper.

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, 10 authors, 4 keywords, 10 MeSH terms, 1 funder, 150 references.

Cite

This paper

van Weperen, V. Y. H., Hoang, J. D., Jani, N. R., Avasthi, S., Chan, C. A., Cao, K., Lokhandwala, Z. A., Emamimeybodi, M., Atmani, K., & Vaseghi, M. (2026). Spinal nociceptive denervation impedes subsequent chronic autonomic remodeling after myocardial infarction in male swine. Nature communications, 17(1), 8955. https://doi.org/10.1038/s41467-026-75759-2

BibTeX

@article{vanweperen2026spinal,
author = {van Weperen, Valerie Y. H. and Hoang, Jonathan D. and Jani, Neil R. and Avasthi, Shail and Chan, Christopher A. and Cao, Kuan and Lokhandwala, Zulfiqar A. and Emamimeybodi, Maryam and Atmani, Karim and Vaseghi, Marmar},
title = {{Spinal nociceptive denervation impedes subsequent chronic autonomic remodeling after myocardial infarction in male swine}},
journal = {Nature communications},
year = {2026},
month = jul,
volume = {17},
number = {1},
pages = {8955},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-75759-2},
url = {https://doi.org/10.1038/s41467-026-75759-2},
pmid = {42637749},
pmcid = {PMC13503775}
}

RIS

TY - JOUR
AU - van Weperen, Valerie Y. H.
AU - Hoang, Jonathan D.
AU - Jani, Neil R.
AU - Avasthi, Shail
AU - Chan, Christopher A.
AU - Cao, Kuan
AU - Lokhandwala, Zulfiqar A.
AU - Emamimeybodi, Maryam
AU - Atmani, Karim
AU - Vaseghi, Marmar
TI - Spinal nociceptive denervation impedes subsequent chronic autonomic remodeling after myocardial infarction in male swine
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/07/22
VL - 17
IS - 1
SP - 8955
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-75759-2
UR - https://doi.org/10.1038/s41467-026-75759-2
LA - en
ER -

CSL-JSON

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