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Multiple system atrophy is associated with brain somatic mutations in clonal hematopoiesis genes

Code ↔ Paper

8 matches between paragraphs of the paper and lines of its authors' code, computed by the harvester (lexical-v1). Click a colored paragraph or line to see its counterpart.

The 8 matches
  1. [1] § Materials and methods › Processing of sequencing data ↔ 2.BAM-DeDuplication/2a_agent_creak.py, lines 1 to 37 · score 0.91 · single strand consensus, CReaK, AGeNT, Hybrid MS1, consensus BAMs, Hybrid MS2 · Report a mismatch
  2. [2] § Materials and methods › Processing of sequencing data ↔ 1.fastq_trim_QC_Align/1c_alignment.py, lines 1 to 29 · score 0.81 · BWA MEM, reference genome, FASTQ, collapse, v0, flag · Report a mismatch
  3. [3] § Materials and methods › Somatic mutation calling and filtering pipeline ↔ 5.Indel-filtering/5d_indel_exclude_repeats.py, lines 1 to 31 · score 0.78 · repetitive regions, RepeatMasker, Duplex consensus, indel VCFs, overlapping, hg38 · Report a mismatch
  4. [4] § Materials and methods › Target gene panel and enrichment strategy ↔ 2.BAM-DeDuplication/2a_agent_creak.py, lines 1 to 37 · score 0.71 · generating consensus sequences, low frequency somatic, somatic variants, tag, molecular, strands · Report a mismatch
  5. [5] § Materials and methods › Somatic mutation calling and filtering pipeline ↔ 2.BAM-DeDuplication/2b_add_read_groups.py, lines 48 to 61 · score 0.63 · Hybrid MS2 BAMs, Duplex BAMs, Hybrid MS1 · Report a mismatch
  6. [6] § Materials and methods › Somatic mutation calling and filtering pipeline ↔ 5.Indel-filtering/5_filter_indels_wrapper.py, lines 62 to 196 · score 0.61 · RepeatMasker, filtering parameters, indel VCFs, quality, hg38, pipeline · Report a mismatch
  7. [7] § Materials and methods › Somatic mutation calling and filtering pipeline ↔ 4.SNV-filtering/4c_filter_read_quality.py, lines 1 to 25 · score 0.58 · mapping quality, strand bias, bp, events, filtered, variants · Report a mismatch
  8. [8] § Materials and methods › Somatic mutation calling and filtering pipeline ↔ 4.SNV-filtering/4_filter_snvs_wrapper.py, lines 61 to 178 · score 0.53 · strand bias, mapping quality, SOR, pipeline, events, filtered · Report a mismatch

Paper

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The authors' code

Python · 356 lines · 11 KB · no license · 2 matches

  1. #!/usr/bin/env python3
  2. """
  3. Step 2a: CReaK Molecular Consensus Calling
  5. Generates and submits SGE jobs to run AGeNT CReaK consensus calling at one or
  6. more stringency levels. Groups reads by MBC and generates consensus sequences
  7. for accurate low-frequency somatic variant detection.
  9. Stringency levels:
  10. MS1 — HYBRID mode, min single strand consensus 1 (maximum sensitivity)
  11. MS2 — HYBRID mode, min single strand consensus 2 (balanced)
  12. DUPLEX — DUPLEX mode (maximum specificity, both strands in agreement required)
  14. Input:
  15. - Directory containing sample subdirectories, each with a sorted BAM
  16. ending in *_sorted.bam (MBC tags must be present from steps 1a-1c)
  18. Output:
  19. - Consensus BAMs in per-stringency subdirectories:
  20. {output_bam_dir}/MS1/{sample}_hybrid_MS1.bam
  21. {output_bam_dir}/MS2/{sample}_hybrid_MS2.bam
  22. {output_bam_dir}/DUPLEX/{sample}_duplex.bam
  24. Requirements:
  25. - AGeNT (v3.1.2 or later)
  26. - Java 17+
  27. - SGE cluster with qsub
  28. - config_2a_agent_creak.yaml
  29. """
  31. import os
  32. import copy
  33. import subprocess
  34. import time
  35. import yaml
  36. import argparse
  37. from pathlib import Path
  40. def load_config(config_path):
  41. """Load configuration from YAML file."""
  42. with open(config_path, 'r') as f:
  43. return yaml.safe_load(f)
  46. def find_sorted_bam(sample_dir, bam_suffix):
  47. """
  48. Find sorted BAM file in a sample directory.
  50. Returns:
  51. Path to BAM file or None if not found.
  52. """
  53. bam_candidates = [f for f in os.listdir(sample_dir) if f.endswith(bam_suffix)]
  55. if len(bam_candidates) == 0:
  56. print(f"Warning: No BAM file found in {sample_dir}")
  57. return None
  58. elif len(bam_candidates) > 1:
  59. print(f"Warning: Multiple BAM files found in {sample_dir}")
  60. print(f" Candidates: {bam_candidates}")
  61. print(f" Using first match: {bam_candidates[0]}")
  63. return os.path.join(sample_dir, bam_candidates[0])
  66. def verify_dependencies(config):
  67. """
  68. Verify required tools exist.
  70. Raises:
  71. FileNotFoundError: If dependencies are missing.
  72. """
  73. agent_path = config['tools']['agent_path']
  74. java_home = config['tools']['java_home']
  76. if not os.path.exists(agent_path):
  77. raise FileNotFoundError(f"AGeNT tool not found: {agent_path}")
  79. if not os.path.exists(java_home):
  80. raise FileNotFoundError(f"Java installation not found: {java_home}")
  82. print(f"✓ AGeNT found: {agent_path}")
  83. print(f"✓ Java found: {java_home}")
  86. def get_output_suffix(consensus_mode, min_stringency):
  87. """Return output BAM suffix based on consensus parameters."""
  88. if consensus_mode.upper() == "DUPLEX":
  89. return "_duplex"
  90. elif consensus_mode.upper() == "HYBRID":
  91. return f"_hybrid_MS{min_stringency}"
  92. else:
  93. return "_consensus"
  96. def create_qsub_script(sample_name, config, input_bam, output_dir, script_dir, stringency_label):
  97. """
  98. Create SGE job script for AGeNT CReaK consensus calling.
  100. Returns:
  101. Path to created job script, or None if output already exists.
  102. """
  103. output_suffix = get_output_suffix(
  104. config['creak']['consensus_mode'],
  105. config['creak']['min_stringency']
  106. )
  108. output_bam = os.path.join(output_dir, f"{sample_name}{output_suffix}.bam")
  110. if os.path.exists(output_bam) and os.path.getsize(output_bam) > 0:
  111. print(f" ⚠ Output already exists: {os.path.basename(output_bam)} (skipping)")
  112. return None
  114. java_home = config['tools']['java_home']
  115. java_env = f"""export JAVA_HOME={java_home}
  116. export PATH={java_home}/bin:$PATH"""
  118. creak_params = config['creak']
  119. creak_cmd = f"""{config['tools']['agent_path']} creak \\
  120. -MD {creak_params['max_distance']} \\
  121. -MS {creak_params['min_stringency']} \\
  122. -c={creak_params['consensus_mode']} \\
  123. -s={creak_params['sample_size']} \\
  124. -mm={creak_params['max_mismatches']} \\
  125. -mr={creak_params['max_read_length']} \\
  126. -mq={creak_params['min_mapping_quality']}"""
  128. if creak_params.get('memory_efficient', True):
  129. creak_cmd += " \\\n --memory-efficient-mode"
  130. if creak_params.get('force_overwrite', True):
  131. creak_cmd += " \\\n -F"
  132. if creak_params.get('filter_mode', True):
  133. creak_cmd += " \\\n -f"
  134. if creak_params.get('retain_singletons', True):
  135. creak_cmd += " \\\n -r"
  137. creak_cmd += f" \\\n -o={output_bam} \\\n {input_bam}"
  139. job_script_template = """#!/bin/bash
  140. #$ -N creak_{sample}_{stringency}
  141. #$ -l h_vmem={memory}
  142. #$ -pe smp {cores}
  143. #$ -l h_rt={wall_time}
  144. #$ -cwd
  145. #$ -o {log_dir}/{sample}_creak_{stringency}.stdout
  146. #$ -e {log_dir}/{sample}_creak_{stringency}.stderr
  148. # Set Java environment (required for AGeNT)
  149. {java_env}
  151. # Verify Java version
  152. java -version
  154. INPUT_BAM={input_bam}
  155. OUTPUT_BAM={output_bam}
  157. echo "Starting AGeNT CReaK for {sample} ({stringency})..."
  158. echo " Input BAM: $(basename $INPUT_BAM)"
  159. echo " Output BAM: $(basename $OUTPUT_BAM)"
  160. echo " Consensus mode: {consensus_mode}"
  161. echo " Minimum stringency: MS{min_stringency}"
  163. # Run AGeNT CReaK
  164. {creak_cmd}
  166. # Verify output
  167. if [ -f "$OUTPUT_BAM" ]; then
  168. SIZE=$(stat -f%z "$OUTPUT_BAM" 2>/dev/null || stat -c%s "$OUTPUT_BAM" 2>/dev/null)
  169. echo "✓ CReaK completed successfully"
  170. echo " Output BAM: $(basename $OUTPUT_BAM)"
  171. echo " File size: $SIZE bytes"
  172. else
  173. echo "✗ ERROR: Output BAM not created"
  174. exit 1
  175. fi
  176. """
  178. job_script = job_script_template.format(
  179. sample=sample_name,
  180. stringency=stringency_label,
  181. memory=config['sge']['memory'],
  182. cores=config['sge']['cores'],
  183. wall_time=config['sge']['wall_time'],
  184. log_dir=output_dir,
  185. java_env=java_env,
  186. input_bam=input_bam,
  187. output_bam=output_bam,
  188. consensus_mode=creak_params['consensus_mode'],
  189. min_stringency=creak_params['min_stringency'],
  190. creak_cmd=creak_cmd
  191. )
  193. job_script_path = os.path.join(script_dir, f"{sample_name}_creak_{stringency_label}.sh")
  194. with open(job_script_path, "w") as f:
  195. f.write(job_script)
  197. return job_script_path
  200. def submit_jobs_in_batches(job_scripts, batch_size, pause_time):
  201. """Submit jobs to SGE in batches."""
  202. for i in range(0, len(job_scripts), batch_size):
  203. batch = job_scripts[i:i + batch_size]
  205. print(f"\n=== Submitting batch {i // batch_size + 1} ({len(batch)} jobs) ===")
  207. for job_script in batch:
  208. result = subprocess.run(
  209. ["qsub", job_script],
  210. capture_output=True,
  211. text=True
  212. )
  213. if result.returncode == 0:
  214. print(f" ✓ Submitted: {os.path.basename(job_script)}")
  215. print(f" {result.stdout.strip()}")
  216. else:
  217. print(f" ✗ Failed: {os.path.basename(job_script)}")
  218. print(f" Error: {result.stderr.strip()}")
  220. if i + batch_size < len(job_scripts):
  221. print(f" Pausing {pause_time}s before next batch...")
  222. time.sleep(pause_time)
  225. def run_stringency(stringency, config, dry_run):
  226. """
  227. Run CReaK pipeline for a single stringency level.
  229. Returns:
  230. List of job scripts generated.
  231. """
  232. cfg = copy.deepcopy(config)
  234. stringency_map = {
  235. 'MS1': {'mode': 'HYBRID', 'min_stringency': 1, 'suffix': 'MS1'},
  236. 'MS2': {'mode': 'HYBRID', 'min_stringency': 2, 'suffix': 'MS2'},
  237. 'DUPLEX': {'mode': 'DUPLEX', 'min_stringency': 2, 'suffix': 'DUPLEX'}
  238. }
  240. stringency_params = stringency_map[stringency]
  241. cfg['creak']['consensus_mode'] = stringency_params['mode']
  242. cfg['creak']['min_stringency'] = stringency_params['min_stringency']
  244. base_output_dir = cfg['paths']['output_bam_dir']
  245. output_dir = os.path.join(base_output_dir, stringency_params['suffix'])
  246. script_dir = cfg['paths']['job_scripts_dir']
  248. os.makedirs(output_dir, exist_ok=True)
  249. os.makedirs(script_dir, exist_ok=True)
  251. print(f"\n{'='*60}")
  252. print(f"Stringency: {stringency}")
  253. print(f"Consensus Mode: {cfg['creak']['consensus_mode']}")
  254. print(f"Min Stringency: MS{cfg['creak']['min_stringency']}")
  255. print(f"Output Directory: {output_dir}")
  256. print(f"{'='*60}\n")
  258. input_dir = cfg['paths']['input_bam_dir']
  259. job_scripts = []
  261. print(f"Scanning for samples in: {input_dir}\n")
  263. for sample in sorted(os.listdir(input_dir)):
  264. sample_dir = os.path.join(input_dir, sample)
  266. if not os.path.isdir(sample_dir):
  267. continue
  269. print(f"Processing sample: {sample}")
  271. input_bam = find_sorted_bam(sample_dir, cfg['bam']['input_suffix'])
  273. if input_bam is None:
  274. print(f" ⚠ Skipping {sample} - BAM file not found\n")
  275. continue
  277. print(f" Input BAM: {os.path.basename(input_bam)}")
  279. job_script_path = create_qsub_script(
  280. sample_name=sample,
  281. config=cfg,
  282. input_bam=input_bam,
  283. output_dir=output_dir,
  284. script_dir=script_dir,
  285. stringency_label=stringency
  286. )
  288. if job_script_path is not None:
  289. job_scripts.append(job_script_path)
  290. print(f" ✓ Job script created: {os.path.basename(job_script_path)}\n")
  291. else:
  292. print()
  294. return job_scripts
  297. def main():
  298. """Main execution function."""
  299. parser = argparse.ArgumentParser(
  300. description='Generate and submit AGeNT CReaK jobs for molecular consensus calling',
  301. epilog='Example: python 2a_agent_creak.py --config config_2a_agent_creak.yaml --stringency MS1 MS2 DUPLEX'
  302. )
  303. parser.add_argument(
  304. '--config',
  305. default='config/04_agent_creak_config.yaml',
  306. help='Path to configuration file (default: config/04_agent_creak_config.yaml)'
  307. )
  308. parser.add_argument(
  309. '--stringency',
  310. choices=['MS1', 'MS2', 'DUPLEX'],
  311. nargs='+',
  312. required=True,
  313. help='One or more stringency levels to run: MS1 MS2 DUPLEX'
  314. )
  315. parser.add_argument(
  316. '--dry-run',
  317. action='store_true',
  318. help='Generate job scripts but do not submit them'
  319. )
  321. args = parser.parse_args()
  323. config = load_config(args.config)
  325. print("Checking dependencies...")
  326. verify_dependencies(config)
  328. all_job_scripts = []
  330. for stringency in args.stringency:
  331. job_scripts = run_stringency(stringency, config, args.dry_run)
  332. all_job_scripts.extend(job_scripts)
  334. print(f"\n{'='*60}")
  335. print(f"Generated {len(all_job_scripts)} job scripts total")
  336. print(f"Stringencies processed: {', '.join(args.stringency)}")
  337. print(f"{'='*60}\n")
  339. if len(all_job_scripts) == 0:
  340. print("No jobs to submit. Exiting.")
  341. return
  343. if args.dry_run:
  344. print("DRY RUN: Jobs not submitted.")
  345. print("Job scripts saved to:", config['paths']['job_scripts_dir'])
  346. else:
  347. submit_jobs_in_batches(
  348. all_job_scripts,
  349. batch_size=config['submission']['batch_size'],
  350. pause_time=config['submission']['pause_between_batches']
  351. )
  352. print("\n✓ All batches submitted successfully")
  355. if __name__ == "__main__":
  356. main()

2a_agent_creak.py at commit e9779fd, no license · at the source

Overview

Authors: Ben Thompson1, Dominic Horner1, Caoimhe Morley1, Emil Gustavsson2,3, Zane Jaunmuktane1,4, Christos Proukakis1
ORCID iDs: Ben Thompson, Emil Gustavsson, Christos Proukakis
  1. Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
  2. UK Dementia Research Institute, University of Cambridge, Cambridge, UK
  3. Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK
  4. Queen Square Brain Bank for Neurological disorders, UCL Queen Square Institute of Neurology, London, UK
Institutions: UCL Queen Square Institute of Neurology (United Kingdom); UK Dementia Research Institute (United Kingdom); University of Cambridge (United Kingdom)
Journal: medRxiv (preprint)
Dates: published online 23 March 2026
Type: Preprint
License: CC BY-ND
Identifiers: DOI 10.64898/2026.03.17.26346081 · OpenAlex W7140105429
Open access: green, a free copy (OpenAlex)
Status: code verified (how the code is found and verified)
Categories: genetics / omics (modality), cellular / molecular (subfield)
Methods: Statistics, Connectivity
Keywords: Multiple system atrophy, somatic mutations, duplex sequencing, clonal haematopoiesis
Topic: Parkinson's Disease Mechanisms and Treatments (Clinical Neurology, Medicine), according to OpenAlex
Funding: Mission MSA; MSA Trust
Citations: not cited yet (Europe PMC); 49 references in the paper

Abstract

The abstract is not reproduced here: the paper's license (CC BY-ND) does not allow it. Read it in the paper, at the publisher or on Europe PMC.

Repository

Its files are read in the Code ↔ Paper reader above, with 8 matches between paragraphs and lines of code.

b-thompson-99/XT-HS2-Small-Somatic

License: none: the authors keep all their rights
State: the link answers, verified on 30 September 2026
Evidence: files inventoried
Commit: e9779fd98ca1408b615e800c1aba940c70973ff5, 23 March 2026
Languages: Python (17)
Size: 35 files, 17 scripts
Software Heritage: not archived
Found in: “Data and code availability”
Holds: README
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: BEDTools (1 file)
Availability: 1 check, the latest on 30 September 2026: the link answers
  • 30 September 2026: the link answers
18 files
At the source: github.com/b-thompson-99/XT-HS2-Small-Somatic

The paper's code and data availability statement is in the Data section.

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  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 17 scripts, each with its path and the digest of its content;
  • 8 matches between paragraphs of the paper and lines of the code (method lexical-v1);
  • neither the text of the paper nor the code itself.

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Read it in the paper: doi.org/10.64898/2026.03.17.26346081.

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Version 1, 30 September 2026: the first record

Recorded: type, journal, dates, 6 authors, 4 keywords, 2 funders, 49 references.

Cite

This paper

Thompson, B., Horner, D., Morley, C., Gustavsson, E., Jaunmuktane, Z., & Proukakis, C. (2026). Multiple system atrophy is associated with brain somatic mutations in clonal hematopoiesis genes. medRxiv (preprint). https://doi.org/10.64898/2026.03.17.26346081

BibTeX

@article{thompson2026multiple,
author = {Thompson, Ben and Horner, Dominic and Morley, Caoimhe and Gustavsson, Emil and Jaunmuktane, Zane and Proukakis, Christos},
title = {{Multiple system atrophy is associated with brain somatic mutations in clonal hematopoiesis genes}},
journal = {medRxiv (preprint)},
year = {2026},
month = mar,
publisher = {medRxiv},
doi = {10.64898/2026.03.17.26346081},
url = {https://doi.org/10.64898/2026.03.17.26346081}
}

RIS

TY - JOUR
AU - Thompson, Ben
AU - Horner, Dominic
AU - Morley, Caoimhe
AU - Gustavsson, Emil
AU - Jaunmuktane, Zane
AU - Proukakis, Christos
TI - Multiple system atrophy is associated with brain somatic mutations in clonal hematopoiesis genes
T2 - medRxiv (preprint)
J2 - medRxiv
PY - 2026
DA - 2026/03/23
PB - medRxiv
DO - 10.64898/2026.03.17.26346081
UR - https://doi.org/10.64898/2026.03.17.26346081
ER -

CSL-JSON

{
"id": "10.64898/2026.03.17.26346081",
"type": "article",
"title": "Multiple system atrophy is associated with brain somatic mutations in clonal hematopoiesis genes",
"container-title": "medRxiv (preprint)",
"author": [
{
"family": "Thompson",
"given": "Ben"
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{
"family": "Horner",
"given": "Dominic"
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{
"family": "Morley",
"given": "Caoimhe"
},
{
"family": "Gustavsson",
"given": "Emil"
},
{
"family": "Jaunmuktane",
"given": "Zane"
},
{
"family": "Proukakis",
"given": "Christos"
}
],
"container-title-short": "medRxiv",
"DOI": "10.64898/2026.03.17.26346081",
"publisher": "medRxiv",
"URL": "https://doi.org/10.64898/2026.03.17.26346081",
"issued": {
"date-parts": [
[
2026,
3,
23
]
]
}
}

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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/10.64898/2026.03.17.26346081.svg)](https://openscicode.org/badge/doi/10.64898/2026.03.17.26346081)
<!-- oscr-badge:end -->
reStructuredText
.. oscr-badge:start

.. image:: https://openscicode.org/badge/doi/10.64898/2026.03.17.26346081.svg
   :target: https://openscicode.org/badge/doi/10.64898/2026.03.17.26346081
   :alt: OSCR

.. oscr-badge:end
HTML
<!-- oscr-badge:start -->
<a href="https://openscicode.org/badge/doi/10.64898/2026.03.17.26346081"><img src="https://openscicode.org/badge/doi/10.64898/2026.03.17.26346081.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.