OSCR

Tyrosyl-tRNA sequestration triggers tyrosyl-tRNA synthetase-associated peripheral neuropathy.

Code ↔ Paper

The paper beside its authors' code: matches between them have not been computed for this paper yet.

Paper

Loaded from Europe PMC by your browser; OSCR does not store it: doi.org · Europe PMC

The paper is loaded when this pane is shown.

The authors' code

R · 120 lines · 3.9 KB · MIT

  1. ### script to calibrate reads based on manual inspection
  3. # load libs
  4. library(foreach)
  5. library(doParallel)
  6. source('functions.R')
  8. # load parameters
  9. conf <- load_mapping_config()
  11. # load tool locations
  12. tool_path <- load_tool_location()
  14. # set max cores
  15. max_cores <- get_max_cores() # from functions.R
  16. # register max 8 cores because filtering process is I/O intense (mainly read and writing)
  17. if(max_cores > 8) {
  18. max_cores <- 8
  19. }
  20. registerDoParallel(makeCluster(max_cores))
  22. # get args
  23. get_dir <- commandArgs(trailingOnly = TRUE)
  25. # check input dir
  26. in_path <- parse_dir(get_dir[1])
  27. if(!dir.exists(in_path)){
  28. stop(
  29. paste0(in_path, ' does not exist!')
  30. )
  31. }
  32. # check if bam files
  33. in_files <- list.files(
  34. path = in_path,
  35. pattern = '.sort.bam',
  36. ignore.case = TRUE
  37. )
  38. if(length(in_files) < 1){
  39. stop('No BAM files found!')
  40. }
  42. # check config for calibration
  43. in_conf <- get_dir[2]
  44. if(grep('.csv$',in_conf) != 1){
  45. stop(paste0(in_conf, ' is not a CSV file!'))
  46. }
  47. # check if 5prime or 3 prime calibration
  48. if(length(grep('5prime',in_conf)) == 1){
  49. firstLast <- 'first'
  50. } else if(length(grep('3prime',in_conf)) == 1){
  51. firstLast <- 'last'
  52. } else {
  53. stop('No "5prime" or "3prime" in the filename of the config file for read calibraton found. Script
  54. does not known whether to perform 5\' or 3\'. Please keep the string "5prime" or "3prime"
  55. filename \n')
  56. }
  58. # read and check
  59. cali_conf <- read.table(in_conf, header = T, stringsAsFactors = F, sep = ',')
  60. if(nrow(cali_conf) < 1){
  61. stop(paste0(in_conf, ' has no rows! No read length processed!'))
  62. }
  63. in_f <- gsub(".sort.bam","",in_files)
  64. in_f2 <- in_f[is.element(in_f,colnames(cali_conf))]
  65. cat(paste0(
  66. length(in_f), ' / ', length(in_f),' found in calibration config file! \n'
  67. ))
  69. # check output dir
  70. out_path <- parse_dir(get_dir[3])
  71. if(!dir.exists(out_path)){
  72. dir.create(out_path)
  73. }
  74. if(!dir.exists(paste0(out_path,'calibration/'))){
  75. dir.create(paste0(out_path,'calibration/'))
  76. }
  77. if(!dir.exists(paste0(out_path,'calibration/calibrated/'))){
  78. dir.create(paste0(out_path,'calibration/calibrated/'))
  79. }
  81. # build vec for parallel exec
  82. par_files <- rep(in_f2, each = nrow(cali_conf) )
  83. par_read_length <- rep(cali_conf[,1], length(in_f2))
  85. ### split by length and take first nucleotide only
  86. cat('Calibrating reads by length and determined nucleotide position ... ')
  87. for_res <- foreach(i = 1:length(par_files)) %dopar% {
  88. # get nucleotide to take
  89. nt <- cali_conf[cali_conf[,1]==par_read_length[i],colnames(cali_conf)==par_files[i]]
  90. # 5' or 3' calibration
  91. if(firstLast == 'first'){
  92. f_read <- paste0("print $1 \"\t\" $2 \"\t\" $3 \"\t\" ($4-1+",nt,"+1) \"\t\" $5 \"\t1M\t\" $7 \"\t\" $8 \"\t\" $9 \"\t\" substr($10,(",nt,"+1),1) \"\t\" substr($11,(",nt,"+1),1); ")
  93. r_read <- paste0("print $1 \"\t\" $2 \"\t\" $3 \"\t\" ($4+length($10)-",nt,"-1) \"\t\" $5 \"\t1M\t\" $7 \"\t\" $8 \"\t\" $9 \"\t\" substr($10,(length($10)+1-",nt,"-1),1) \"\t\" substr($11,(length($11)+1-",nt,"-1),1); ")
  94. } else if(firstLast == 'last') {
  95. r_read <- paste0("print $1 \"\t\" $2 \"\t\" $3 \"\t\" ($4-1+",nt,"+1) \"\t\" $5 \"\t1M\t\" $7 \"\t\" $8 \"\t\" $9 \"\t\" substr($10,(",nt,"+1),1) \"\t\" substr($11,(",nt,"+1),1); ")
  96. f_read <- paste0("print $1 \"\t\" $2 \"\t\" $3 \"\t\" ($4+length($10)-",nt,"-1) \"\t\" $5 \"\t1M\t\" $7 \"\t\" $8 \"\t\" $9 \"\t\" substr($10,(length($10)+1-",nt,"-1),1) \"\t\" substr($11,(length($11)+1-",nt,"-1),1); ")
  97. }
  98. # check if NA or > 0
  99. if(!is.na(nt) && !is.null(nt) && nt > 0){
  100. # run
  101. system(
  102. paste0(
  103. tool_path['samtools'],' view -h ',
  104. in_path,par_files[i],'.sort.bam',
  105. " | awk '$1 ~ /@/ || length($10) == ",par_read_length[i],"'",
  106. " | awk '{
  107. if($1 ~ /@/)
  108. print $0;
  109. else if($2 == 0)
  110. ",f_read,"
  111. else if($2 == 16)
  112. ",r_read,"
  113. }'",
  114. ' | ',tool_path['samtools'],' view -S -b - > ',
  115. out_path,'calibration/calibrated/',gsub(".sort.bam","",par_files[i]),'_',par_read_length[i],'_calibrated.bam'
  116. )
  117. )
  118. }
  119. }
  120. cat('DONE \n')

calibrate_reads.R at commit f0751f3, under MIT · at the source

Overview

Authors: Moushami Mallik1, Abigail L D Tadenev2, Natalia Mora1, Vanessa Lewandowski3, Daniel Köster3, María Landínez-Macías1, Robin Thompson3, María P Menafra1, Noah K Taylor4, Pascal van Lith1, Nick van Bakel1, Marica Catinozzi1, Scott Q Harper4,5, Zoya Ignatova3, Robert W Burgess2, Erik Storkebaum1
ORCID iDs: Zoya Ignatova, Robert W Burgess, Erik Storkebaum
  1. Molecular Neurobiology Laboratory, Donders Institute for Brain, Cognition and Behaviour and Faculty of Science, Radboud University, Nijmegen 6525 AJ, The Netherlands
  2. The Jackson Laboratory, Bar Harbor, ME 04609, USA
  3. Biochemistry and Molecular Biology, Department of Chemistry, University of Hamburg, Hamburg 20146, Germany
  4. Jerry R. Mendell Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43202, USA
  5. Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43201, USA
Institutions: Radboud University Nijmegen (Netherlands); Donders Institute for Brain, Cognition and Behaviour (Netherlands); Jackson Laboratory (United States); Universität Hamburg (Germany); Nationwide Children's Hospital (United States); Abigail Wexner Research Institute (United States); The Ohio State University (United States)
Journal: Brain : a journal of neurology, volume 149, issue 11, pages 4052-4065
Dates: received 6 February 2026; accepted 27 May 2026; published online 12 August 2026; in print November 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1093/brain/awag204 · PMID 42703926 · PMCID PMC13730582 · OpenAlex W7211900003
Open access: hybrid, a free copy (OpenAlex)
Status: code verified (how the code is found and verified)
Categories: human (organism), mouse (organism), drosophila (organism), other condition (population)
Methods: Preprocessing, Spectral & time-frequency, Statistics, Evoked potentials, Connectivity, fMRI & imaging, Physiology & signal measures
Keywords: Charcot–Marie–Tooth disease, peripheral neuropathy, aminoacyl-tRNA synthetase, molecular mechanism, gene therapy, integrated stress response
MeSH: Charcot-Marie-Tooth Disease*, Peripheral Nervous System Diseases*, RNA, Transfer, Tyr*, Tyrosine-tRNA Ligase*, Animals, Animals, Genetically Modified, Disease Models, Animal, Drosophila, Humans, Mice, Mice, Transgenic, Motor Neurons, Mutation (* major topic)
Topic: Hereditary Neurological Disorders (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: European Research Council; Radala Foundation; Stichting ALS Nederland; AFM-Téléthon (French Muscular Dystrophy Association); ARSLA; Prinses Beatrix Spierfonds; Muscular Dystrophy Association; EU Joint Programme; JPND; Health~Holland; Biotech Booster; DI-NIN Fund; NWO Take-off WO Phase I; Donders Center for Neuroscience; Deutsche Forschungsgemeinschaft; national institutes of health
Citations: not cited yet (Europe PMC); 36 references in the paper

Abstract

Mono-allelic mutations in seven cytosolic aminoacyl-tRNA synthetase genes cause Charcot–Marie–Tooth (CMT) peripheral neuropathy.

Here, we report that tyrosyl-tRNA (tRNATyr) sequestration by CMT-mutant tyrosyl-tRNA synthetase (TyrRS) is the molecular root cause of CMT-YARS1. tRNATyr sequestration depletes the cellular free tRNATyr pool, leading to insufficient tyrosyl-tRNATyr production and ribosome stalling at tyrosine codons.

In three Drosophila CMT-YARS1 models, transgenic overexpression of tRNATyr rescued peripheral neuropathy phenotypes and defective mRNA translation. We provide biochemical evidence for tRNATyr sequestration by the three CMT-TyrRS variants expressed in the Drosophila models and ribosome profiling revealed selective ribosome pausing at the two tyrosine codons. In the Yars1E196K mouse model, adeno-associated virus serotype 9 (AAV9)-mediated overexpression of tRNATyr—but not wild-type TyrRS protein—fully rescued motor performance deficits, reduced nerve conduction velocity and reduced motor axon calibre. Furthermore, AAV9-tRNATyr gene therapy prevented activation of the integrated stress response in spinal motor neurons, indicating resolution of ribosome stalling.

Thus, elevating tRNATyr levels constitutes a novel therapeutic approach for CMT-YARS1.

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

Repository

Its files are read in the Code ↔ Paper reader above.

AlexanderBartholomaeus/MiMB_ribosome_profiling

License: MIT
State: the link answers, verified on 5 November 2026
Evidence: files inventoried
Commit: f0751f30d91d10de0281ae98a49724c4f21c2ff9, 7 April 2020
Languages: R (14)
Size: 26 files, 14 scripts
Software Heritage: not archived
Found in: the text, “Ribosome profiling”
Holds: README, license file
Not found: CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 5 November 2026: the link answers
  • 5 November 2026: the link answers
16 files
At the source: github.com/AlexanderBartholomaeus/MiMB_ribosome_profiling

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;
  • 14 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • 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

Ribosome profiling data were deposited in the Gene Omnibus (GEO) under the accession number GSE268213. Any newly generated materials, including DNA constructs and fly lines reported in this paper, are available from the corresponding author () upon request.

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, 5 November 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 16 authors, 6 keywords, 13 MeSH terms, 16 funders, 0 references.

Cite

This paper

Mallik, M., Tadenev, A. L. D., Mora, N., Lewandowski, V., Köster, D., Landínez-Macías, M., Thompson, R., Menafra, M. P., Taylor, N. K., van Lith, P., van Bakel, N., Catinozzi, M., Harper, S. Q., Ignatova, Z., Burgess, R. W., & Storkebaum, E. (2026). Tyrosyl-tRNA sequestration triggers tyrosyl-tRNA synthetase-associated peripheral neuropathy. Brain : a journal of neurology, 149(11), 4052-4065. https://doi.org/10.1093/brain/awag204

BibTeX

@article{mallik2026tyrosyl,
author = {Mallik, Moushami and Tadenev, Abigail L D and Mora, Natalia and Lewandowski, Vanessa and Köster, Daniel and Landínez-Macías, María and Thompson, Robin and Menafra, María P and Taylor, Noah K and van Lith, Pascal and van Bakel, Nick and Catinozzi, Marica and Harper, Scott Q and Ignatova, Zoya and Burgess, Robert W and Storkebaum, Erik},
title = {{Tyrosyl-tRNA sequestration triggers tyrosyl-tRNA synthetase-associated peripheral neuropathy}},
journal = {Brain : a journal of neurology},
year = {2026},
month = nov,
volume = {149},
number = {11},
pages = {4052--4065},
publisher = {Oxford University Press},
issn = {0006-8950},
doi = {10.1093/brain/awag204},
url = {https://doi.org/10.1093/brain/awag204},
pmid = {42703926},
pmcid = {PMC13730582}
}

RIS

TY - JOUR
AU - Mallik, Moushami
AU - Tadenev, Abigail L D
AU - Mora, Natalia
AU - Lewandowski, Vanessa
AU - Köster, Daniel
AU - Landínez-Macías, María
AU - Thompson, Robin
AU - Menafra, María P
AU - Taylor, Noah K
AU - van Lith, Pascal
AU - van Bakel, Nick
AU - Catinozzi, Marica
AU - Harper, Scott Q
AU - Ignatova, Zoya
AU - Burgess, Robert W
AU - Storkebaum, Erik
TI - Tyrosyl-tRNA sequestration triggers tyrosyl-tRNA synthetase-associated peripheral neuropathy
T2 - Brain : a journal of neurology
J2 - Brain
PY - 2026
DA - 2026/11/01
VL - 149
IS - 11
SP - 4052
EP - 4065
SN - 0006-8950
PB - Oxford University Press
DO - 10.1093/brain/awag204
UR - https://doi.org/10.1093/brain/awag204
LA - en
ER -

CSL-JSON

{
"id": "10.1093/brain/awag204",
"type": "article-journal",
"title": "Tyrosyl-tRNA sequestration triggers tyrosyl-tRNA synthetase-associated peripheral neuropathy",
"container-title": "Brain : a journal of neurology",
"author": [
{
"family": "Mallik",
"given": "Moushami"
},
{
"family": "Tadenev",
"given": "Abigail L D"
},
{
"family": "Mora",
"given": "Natalia"
},
{
"family": "Lewandowski",
"given": "Vanessa"
},
{
"family": "Köster",
"given": "Daniel"
},
{
"family": "Landínez-Macías",
"given": "María"
},
{
"family": "Thompson",
"given": "Robin"
},
{
"family": "Menafra",
"given": "María P"
},
{
"family": "Taylor",
"given": "Noah K"
},
{
"family": "van Lith",
"given": "Pascal"
},
{
"family": "van Bakel",
"given": "Nick"
},
{
"family": "Catinozzi",
"given": "Marica"
},
{
"family": "Harper",
"given": "Scott Q"
},
{
"family": "Ignatova",
"given": "Zoya"
},
{
"family": "Burgess",
"given": "Robert W"
},
{
"family": "Storkebaum",
"given": "Erik"
}
],
"container-title-short": "Brain",
"volume": "149",
"issue": "11",
"page": "4052-4065",
"DOI": "10.1093/brain/awag204",
"PMID": "42703926",
"PMCID": "PMC13730582",
"ISSN": "0006-8950",
"publisher": "Oxford University Press",
"URL": "https://doi.org/10.1093/brain/awag204",
"language": "en",
"issued": {
"date-parts": [
[
2026,
11,
1
]
]
}
}

The tracing map gets a citation of its own once an author has validated it and it has a DOI.

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1073/pnas.2317864121
tRNA modification enzyme-dependent redox homeostasis regulates synapse formation and memory.
Journal: Proceedings of the National Academy of Sciences of the United States of America
In common: drosophila, author Erik Storkebaum
[2] doi:10.1038/s41467-022-35724-1 [code]
Integrative genetic analysis illuminates ALS heritability and identifies risk genes.
Journal: Nature communications
In common: other condition, author Erik Storkebaum

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Add the badge to the code's README

OSCR: the badge of this paper

If you are an author or a maintainer of this paper's code, you can add this badge. It says what OSCR knows of the paper (its code, its validated tracing map) and links the code to this page. Paste one of these snippets under the README's title. Keep the two marks around it, so that the badge can be replaced in place and is never added twice. OSCR changes nothing in your repository.

Markdown
<!-- oscr-badge:start -->
[![OSCR](https://openscicode.org/badge/doi/10.1093/brain/awag204.svg)](https://openscicode.org/badge/doi/10.1093/brain/awag204)
<!-- oscr-badge:end -->
reStructuredText
.. oscr-badge:start

.. image:: https://openscicode.org/badge/doi/10.1093/brain/awag204.svg
   :target: https://openscicode.org/badge/doi/10.1093/brain/awag204
   :alt: OSCR

.. oscr-badge:end
HTML
<!-- oscr-badge:start -->
<a href="https://openscicode.org/badge/doi/10.1093/brain/awag204"><img src="https://openscicode.org/badge/doi/10.1093/brain/awag204.svg" alt="OSCR"></a>
<!-- oscr-badge:end -->

On GitHub, open the README, choose Edit (the pencil), paste the snippet under the title, then "Commit changes".

If you choose to, you can have the badge kept up to date for you, with oscr badge --write from the command line or with the GitHub Action in your repository's workflows. Every other form and option (a card, AsciiDoc, LaTeX, shields.io) is on the badge page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: code errors and mismatches between the code and the paper about this paper and its code, from readers and its authors, beside the paper and its tracing map.

Report a mismatch between the code and the paper · Report a code error (signed in)

Reproductions: reports from readers who ran the authors' code and did not get the paper's result, what they ran, with which environment, commit and data.

Report a reproduction failure (signed in)

Versions of its code: the releases of its code tied to a version of this paper (the preprint, the accepted manuscript, the version of record…), each with the tracing map versioned with it.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.