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Discovery of Early-Branching Wolbachia Reveals Functional Enrichment on Horizontally Transferred Genes.

Front Microbiol · 2022
L1 90/100 3/4
⚑ Flagged for review — a reproduced result did not match the reported value

Provisional — an automated or curator check raised a specific concern and points reviewers here. This is NOT a final assessment and not a determination about the authors.

Why this verdict

The main results reproduced: recomputed values matched the published ones within tolerance.

Reproduced on the brainbox compute brainarbeit.com
Scoring basis — itemised

Every item that counted toward this verdict, and the exact part of the reproduction that produced it.

Supporting (toward a concern)
Content-critical question only partially held
+2 pts
From: Q7 · Core claim 🟡
Content-critical question only partially held
+2 pts
From: Q8 · Severity of the miss (overall human judgment) 🟡
Minor / cosmetic deviation
+1 pts
From: Q3 · Location of the main deviation 🟡
Minor / cosmetic deviation
+1 pts
From: Q4 · Cause of the deviation 🟡
Concordant (toward reproduced)
Code + data deposited & functional
-2 pts
From: Data & code availability Available & functional
Total score +4
✓ What held up
  • Same input data as the authors
  • Reported values were directly comparable
  • Reported values are derivable from the shared data
  • Any deviation was negligible
What did not (or only partly)
  • 🟡A deviation arose in the data or preprocessing
  • 🟡A deviation was attributed to the published material
  • 🟡The central claim did not (fully) hold under reproduction
  • 🟡Overall, the reproduction showed a material discrepancy
How its reproducibility compares
90/100
Reproducibility score
0.9 SD above mean
vs. all fields · 1173 studies
🎯 Scores higher than 79% of all assessed papers rank 211 of 1173 scored

A 0–100 reproducibility-quality score from the per-question grades, shown as a z-score: standard deviations above (+) or below (−) the mean of comparable assessments.

Reproduction agent’s raw note

REPRODUCED (1:1, described well enough). Table 1 comparative genome stats for all 6 Wolbachia strains reproduced from the publicly deposited FASTAs using the LINKED third-party tool barrnap (rRNA) + Prokka 1.14.6 (genes/tRNA) + seqkit (length/GC/contigs/N50/max): 32 exact, 6 within-tol, 6 mismatch of 44 graded values. Length & contig counts EXACT for all 6 (wTex off 1 bp). barrnap rRNA = 3 EXACT for all. Prokka CDS = reported Genes EXACT for 5/6 (wTex within 2). tRNA EXACT for all once Prokka's separately-reported tmRNA (=1) is added (paper's 'tRNAs' = tRNA+tmRNA). GC within-tol, with shortfalls fully explained by N-base handling (exact where deposit has 0 N's). wTex N50 (10082) and max-scaffold (57862) EXACT. The ONLY mismatches are the 6 pseudogene counts: plain Prokka does not call pseudogenes (the paper's values come from NCBI PGAP, a different annotation source) -- an honest pipeline limitation, not a fabrication signal. Stretch 16S divergence partial (wTex-wPpe 3.805% vs paper's max-of-trio 4.211%; wRad genome not provided). NOT attempted: wet-lab, manual Geneious curation, de-novo wTex re-assembly, HGT calls, GO/dN-dS enrichment, phylogeny supports, the unpublished ~3,400-amplicon SRA screen, ModelSEED, CheckM/coverage.

These records describe the outcome of reproduction attempts carried out autonomously by brainbox using large language models (LLMs). They are not peer review, not an audit, and not a determination of error or misconduct by any author. A verdict reflects what one attempt could or could not reproduce — which may depend on data access, undocumented parameters, the computing environment, or the depth of effort — and not a judgement of the people who did the work. We can be wrong, and we correct mistakes quickly: every record carries a “report an error” button.

Assessment versions

Every reproduction run is kept as an immutable version — anchored to the data as it stood, with a tamper-evident chain hash. A rerun (e.g. after an author updates a deposit) adds a new version; the previous one stays on record.

  1. v1 current initial assessment Score 90
    assessed: 2026-06-21 ⛓ d95094057560
✎ I am an author of this paper

Updated or fixed a deposit, or is there an erratum? Ask us to re-run the metrics. We verify by email first; the new result is published as a new version with full history — nothing is overwritten.

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Provenance — full disclosure

When this reproduction was carried out, which methodology version was used, and by whom — so the record can be audited and checked independently.

Reproduced
2026-06-21
Rubric version
v1.0
Assessed by
🤖 AI curator · claude (ai-curator room) · v1.0 · run #1 2026-06-21
no human curator yet
Last updated
2026-08-05

Provisional, curator- or AI-assessed, and independently checkable. A reproduction outcome states what one attempt could reproduce — not a judgement of the authors.

Deep full-text extraction

Model: sonnet
Founding hypothesis

The study tests whether early-branching Wolbachia symbionts of plant-parasitic nematodes (PPNs) show genomic and functional signatures reflecting plant-specialization as a key driver of early Wolbachia evolution, positioning them functionally between mutualist and reproductive-parasite Wolbachia strains.

Core claims
  • A novel early-branching Wolbachia strain (wTex), one of the earliest supergroup L strains, was discovered in a plant-parasitic nematode community from 1 of 16 sampled sites. finding
  • wTex lacks known genes for cytoplasmic incompatibility, riboflavin, and biotin biosynthesis, placing it functionally between mutualist C+D strains and reproductive parasite A+B strains. finding
  • Functional terms enriched in supergroup L Wolbachia include protoporphyrinogen IX, thiamine, lysine, fatty acid, and cellular amino acid biosynthesis. finding
  • dN/dS analysis indicates the strongest purifying selection on arginine and lysine metabolism, and on vitamin B6, heme, and zinc ion binding pathways. finding
  • PPN Wolbachia contains putative horizontally transferred genes, including a Midichloria-like lysine biosynthesis operon, a spirochete-like thiamine operon shared with wCfeT, a Rickettsia-like ATP/ADP carrier, and a eukaryote-like gene implicated in the lysine-to-pipecolic acid systemic acquired resistance pathway. mechanism
  • Group L-like Wolbachia variants were identified in global rhizosphere sequence databases, suggesting additional undiscovered PPN Wolbachia diversity. finding
  • An iterative subtractive mapping and reassembly approach (bwa mapping + metaSPAdes) was developed to recover Wolbachia metagenome-assembled genomes from mixed nematode community DNA. method
  • Higher dN/dS pathways distinguish group L Wolbachia from wPni (aphids), wFol (springtails), and wCfeT (cat fleas), indicating distinct functional shifts across early host transitions. finding
Experimental setups
Assay System Perturbation Readout Platform
Metagenomic shotgun sequencing / genome skimming rhizosphere nematode community DNA (soil/root samples) none de novo assembled Wolbachia-like contigs/genome (MAG) Illumina HiSeq, 150 PE cycles
PCR pre-screening (16S rRNA) total nematode community DNA none presence/absence of Wolbachia 16S rRNA sequence custom primers (Wol-mee-F/R) thermal cycler
Comparative genomics / gene presence-absence analysis wTex genome vs. other Wolbachia and Anaplasmataceae outgroups none gene repertoire and pathway presence/absence Roary v3.13
Metabolic pathway modeling wTex genome none metabolic pathway completeness (KEGG/MetaCyc) ModelSEED v2.6.1
Phylogenomic/phylogenetic analysis (16S rRNA, COI, concatenated genes) Wolbachia strains and candidate nematode hosts none evolutionary relationships/tree topology, bootstrap/posterior support RAxML v4 (ML), MrBayes v2.2.4 (Bayesian)
dN/dS selection analysis Wolbachia coding genes across strains/pathways none signatures of purifying/positive selection per pathway
SRA metadata/read screening public NCBI SRA sequencing projects (rhizosphere, soil, nematode) none presence of Wolbachia-like 16S rRNA reads NCBI E-utilities, blastn
Community abundance correlation analysis 21 sampled rhizosphere nematode communities (COI reads) none Spearman rank correlation between nematode taxon abundance and Wolbachia 16S rRNA coverage R package Hmisc (rcorr), corrplot
Key results
  • 1 of 16 sampled sites harbored nematode communities hosting a PPN Wolbachia strain (wTex) 1/16 sites
  • wTex lacks genes for cytoplasmic incompatibility, riboflavin, and biotin biosynthesis
  • Functional enrichment in group L for protoporphyrinogen IX, thiamine, lysine, fatty acid, and amino acid biosynthesis
  • Strongest purifying selection (dN/dS) found on arginine and lysine metabolism, vitamin B6, heme, and zinc ion binding pathways
  • Identification of putative HGT genes: Midichloria-like lysine operon, spirochete-like thiamine operon (shared with wCfeT), Rickettsia-like ATP/ADP carrier, eukaryote-like pipecolic acid pathway gene
  • Group L-like Wolbachia variants detected in global rhizosphere sequence databases
  • Higher dN/dS pathways differentiate group L from wPni, wFol, and wCfeT, indicating distinct functional changes across early host transitions
Key statistics
  • count 1 out of 16 (sampled sites with PPN Wolbachia-positive nematode communities)
  • count 800–1,400 (nematodes processed per sample for DNA extraction)
  • other 0.6–1 μg (DNA input for genomic library preparation)
  • other 150 PE cycles (Illumina HiSeq sequencing read length)
  • correlation Spearman rho with BH-adjusted p-values (correlation between nematode COI abundance and Wolbachia 16S rRNA coverage across communities)
  • other up to 25% global crop yield loss / ~$100 billion annually (economic/agricultural impact of plant-parasitic nematodes)
  • count 3 gene regions (sequence data available for comparison strain wRad)
  • other chain length 1,100,000; 4 heated chains; burn-in 100,000 (MrBayes MCMC settings for COI phylogenetic analysis)

Statistical methods review

Model: sonnet

A neutral, descriptive read of the statistical approach — what was done, and (for shared learning, not as criticism) what could also have been done.

This study used metagenomic assembly and comparative/phylogenomic bioinformatics rather than classical wet-lab experimental statistics: nematode community composition (from COI barcode abundance) was related to Wolbachia abundance across 21 sampled communities using Spearman rank correlation with Benjamini-Hochberg-adjusted p-values, phylogenetic relationships were reconstructed with maximum-likelihood (RAxML, bootstrap support) and Bayesian (MrBayes, MCMC convergence diagnostics) methods, and gene/pathway-level selection was assessed via dN/dS analysis referenced in the abstract. Results are reported primarily as correlation coefficients (rho) with adjusted p-values, phylogenetic trees with bootstrap/posterior support values, and descriptive gene presence-absence and functional enrichment comparisons across strains.

Replicationunclear Sample size21 sampled nematode communities were compared for community/Wolbachia correlation analysis; for genome assembly, reads from multiple samples from the same farm were combined/pooled to improve coverage rather than treated as independent replicates GroupsNematode taxon abundance vs. Wolbachia abundance across sampled communities; Wolbachia strains/supergroups compared for gene content and selection signatures Pairingna Randomization/blindingnot stated Dispersionunclear Effect sizesyes Multiplicity correctionBenjamini-Hochberg (BH) false discovery rate correction
Statistical tests used
Test Applied to n Assumptions
Spearman rank correlation (rho) Correlation between nematode taxon (COI-based) relative abundance and Wolbachia 16S rRNA relative abundance across sampled nematode communities 21 sampled nematode communities not stated
dN/dS (nonsynonymous/synonymous substitution rate) analysis Comparison of selection pressure across metabolic pathways/genes between Wolbachia group L and related strains (wPni, wFol, wCfeT) not stated
Maximum likelihood phylogenetic reconstruction with bootstrap support (RAxML, GTR+Gamma) Phylogenies of candidate PPN hosts (COI) and of Wolbachia strains (16S rRNA and concatenated gene regions) 500 bootstrap replicates na
Bayesian phylogenetic inference (MrBayes, MCMC) Same phylogenetic datasets as above (COI and Wolbachia strain relationships) chain length 1,100,000; burn-in 100,000; convergence checked with minESS > 200 na
Approaches that could also have been used
  • The relationship between nematode taxon abundance and Wolbachia abundance across communities was assessed using Spearman rank correlation on relative-abundance data, with BH FDR correction applied across the resulting p-value matrix.
    Could also: Compositional-data-aware methods such as centered-log-ratio (CLR) transformation followed by correlation, or tools like SparCC/SCC designed for relative-abundance microbiome data — Relative abundance data are compositional (constrained to sum to a whole), and compositional-aware correlation methods can also help distinguish genuine co-occurrence from artifacts of the closure constraint, complementing the Spearman approach already used.
  • Node support for phylogenetic relationships was evaluated with maximum-likelihood bootstrapping (500 replicates) and separately with Bayesian posterior probabilities.
    Could also: Additional support metrics such as SH-aLRT or ultrafast bootstrap approximations (e.g., in IQ-TREE), or running multiple independent MCMC chains with PSRF/ESS diagnostics — These approaches can also provide complementary or faster-converging measures of node reliability and additional convergence diagnostics alongside the bootstrap and minESS metrics already reported.
  • Selection pressure across pathways/genes was summarized using gene-wide or pathway-wide dN/dS ratios to identify signatures of purifying selection.
    Could also: Site-specific or branch-site selection models such as PAML's branch-site test or HyPhy's FEL/MEME — These methods could also resolve selection signals at the level of individual codons or specific lineages, offering finer-grained detail than an aggregate dN/dS ratio for a gene or pathway.
  • Functional term enrichment in supergroup L genomes is described narratively (e.g., pathways 'enriched') based on gene presence-absence comparisons via Roary and ModelSEED.
    Could also: A formal statistical enrichment test, such as a hypergeometric/Fisher's exact test or permutation-based gene-set enrichment analysis — A formal enrichment test could also quantify the statistical significance of pathway overrepresentation, complementing the descriptive presence-absence comparison already performed.
  • Correlation results are reported as Spearman rho and adjusted p-values without an explicit mention of confidence intervals.
    Could also: Bootstrap-derived confidence intervals around the Spearman rho estimates — Reporting a confidence interval alongside rho and the p-value could also convey the precision of the correlation estimate, which is particularly informative given the modest number (21) of sampled communities.
  • Wolbachia detection was positive in only 1 of 16 sampled sites, with samples from that site subsequently combined/pooled to improve genome assembly coverage.
    Could also: A formal detection-sensitivity or rarefaction/accumulation-curve analysis across sampling sites — Such an analysis could also characterize how sampling effort relates to the likelihood of detecting a low-prevalence symbiont, complementing the qualitative positive/negative site tally already presented.
Software: R / Hmisc (rcorr function) Hmisc 4.5-0 · R (p.adjust, method BH) · R / corrplot · RAxML 4 · MrBayes 2.2.4 · FastTree 2.1.11 · ModelSEED 2.6.1

What was reproduced

The exact results taken into scope, with each reported value next to the value our attempt produced.

Scope — pmid-35547116

Paper: Lefoulon et al. (2022) Discovery of Early-Branching Wolbachia Reveals Functional Enrichment on Horizontally Transferred Genes. Front. Microbiol. 13:867392. DOI 10.3389/fmicb.2022.867392 · PMCID PMC9084900.

Linked code: https://github.com/tseemann/barrnap — a third-party rRNA-prediction tool (used by the authors inside Prokka). Per BRIEF rule P16, applying this existing third-party tool to the paper's own data is an equally valid reproduction. barrnap detects 5S/16S/23S rRNA in a genome FASTA → GFF3.

Linked data: SRA BioProject PRJNA687334 (raw Illumina HiSeq metagenome reads of nematode pools); plus a set of public NCBI genome assemblies used for comparative analysis (the wTex assembly the authors deposited + 5 reference Wolbachia genomes).


In scope (pipeline-derived, public data, reproducible)

A. Table 1 — comparative genome statistics for 6 Wolbachia strains ← PRIMARY 1:1 TARGET

The authors deposited/used 6 assembled genomes. All are public on NCBI. The Table 1 columns are deterministic functions of those FASTAs + the Prokka/barrnap annotation pipeline the Methods describe ("Prokka v1.14.6 using Prodigal, HMMER3, BLAST+, Barrnap for rRNAs, Aragorn for tRNAs"):

column how reproduced determinism
Total length (bp) sum of contig lengths from FASTA exact (FASTA only)
%GC base composition from FASTA exact (FASTA only)
# contigs/scaffolds count of records in FASTA exact (FASTA only)
rRNAs barrnap (the linked tool) exact/within-tol
tRNAs Prokka → Aragorn within-tol (version-sensitive)
Genes Prokka → Prodigal within-tol (version-sensitive)
Pseudogenes Prokka within-tol

Strains + accessions (Table 1 / Data availability):

  • wTex — JAIXMJ000000000 (GenBank WGS; this study)
  • wPpe — NZ_MJMG01000001.1 (RefSeq WGS)
  • wPni — JACVWV010000040.1 (GenBank WGS)
  • wFol — NZ_CP015510.2 (RefSeq complete)
  • wCfeT — NZ_CP051156.1 (RefSeq complete)
  • wChem — NZ_CP061738.1 (RefSeq complete)

Pipeline: barrnap 0.9+ (rRNA) + Prokka 1.14.6 (genes/tRNA/pseudogenes) + plain FASTA stats (length/GC/contigs/N50).

B. 16S rRNA sequence divergence (HARDER, stretch)

Reported: max 16S difference among wTex/wPpe/wRad = 4.211%; PPN-clade vs wPni avg 3.934%. Reproduce by extracting 16S with barrnap from each genome, aligning (MAFFT), computing pairwise %identity. Caveat: wRad accession not given in the paper's data table → may only partially reproduce (wTex vs wPpe).

C. wTex de-novo assembly from PRJNA687334 (HARDEST, stretch — likely partial)

Reported wTex stats (1,013,022 bp, 33.49% GC, 192 scaffolds, N50 10,082, 989 genes). Full iterative subtractive metaSPAdes pipeline. Exact reproduction is infeasible because the published Methods include manual curation in Geneious Prime (proprietary, no license) + a hand-tuned 3-round subtractive read-extraction loop. We can attempt a single metaSPAdes pass for an order-of-magnitude sanity check only, not a 1:1 match.


Out of scope (wet-lab / manual / external / non-reproducible)

  • Field sampling, nematode isolation (Baermann/sucrose), DNA extraction, PCR pre-screen — wet-lab.
  • Manual genome curation in Geneious Prime v2020.0.4 (ProgressiveMauve/LASTZ) — proprietary GUI, no license, manual.
  • HGT identification (asd2/lysC, sdh, thiE/thiM/thiD, tlcA, BON/deoC, PCBD1) — manual BLAST + synteny interpretation, no scripted entrypoint.
  • GO enrichment (topGO weight01.fisher) + dN/dS (KaKs Calculator) — depend on Roary ortholog sets and specific PRANK alignments not shipped; reproducible in principle but no released ortholog tables → not a clean 1:1; deferred.
  • Phylogenetic bootstrap/posterior support (RAxML/MrBayes) — depend on specific alignments + curation not deposited; not a clean numeric comparison.
  • SRA screening of "~3,400 amplicon experiments" → 81 runs / 61 unique seqs — the exact query list / 3,400-experiment set
Figures / tables: Table
wTex_len
Reported
1013022
Reproduced
1013021
within tolerance
wTex_contigs
Reported
192
Reproduced
192
exact
wTex_genes
Reported
989
Reproduced
987
within tolerance
wTex_rRNA
Reported
3
Reproduced
3
exact
wTex_tRNA
Reported
38
Reproduced
38
exact
wTex_pseudo
Reported
2
Reproduced
did not match
wTex_n50
Reported
10082
Reproduced
10082
exact
wTex_maxscaf
Reported
57862
Reproduced
57862
exact
wPpe_len
Reported
975127
Reproduced
975127
exact
wPpe_contigs
Reported
12
Reproduced
12
exact
wPpe_genes
Reported
962
Reproduced
962
exact
wPpe_tRNA
Reported
36
Reproduced
36
exact
wPni_len
Reported
1457187
Reproduced
1457187
exact
wPni_contigs
Reported
182
Reproduced
182
exact
wPni_genes
Reported
1314
Reproduced
1314
exact
wFol_len
Reported
1801626
Reproduced
1801626
exact
wFol_genes
Reported
1601
Reproduced
1601
exact
wFol_gc
Reported
34.35
Reproduced
34.35
exact
wCfeT_len
Reported
1495538
Reproduced
1495538
exact
wCfeT_genes
Reported
1519
Reproduced
1519
exact
wChem_len
Reported
1291339
Reproduced
1291339
exact
wChem_genes
Reported
1266
Reproduced
1266
exact
all_rRNA_barrnap
Reported
3 per strain (1x5S+1x16S+1x23S)
Reproduced
3 per strain
exact
all_pseudogenes
Reported
2/9/4/11/55/41
Reproduced
0 (plain Prokka has no pseudogene caller)
did not match
s16_wTex_wPpe
Reported
max trio 4.211% (incl. wRad, no accession)
Reproduced
wTex-wPpe 3.805%
partial

Assessments & scoring basis

Each contributor’s verdict, the per-question basis, and the auditable, itemised worksheet behind it.

🤖 AI curator · claude (ai-curator room) · v1.0 L1 90/100

An automated assessment. It can flag an open question for review but can never, on its own, record a discrepancy verdict (C5) against a paper.

🟢1. Data identity
🟢2. Endpoint comparability
🟡3. Location of the main deviation
🟡4. Cause of the deviation
🟢5. Derivability / plausibility
🟢6. Severity of the deviation
🟡7. Core claim
🟡8. Severity of the miss (overall human judgment)
Scoring basis — itemised

Every item that counted toward this verdict, and the exact part of the reproduction that produced it.

Supporting (toward a concern)
Content-critical question only partially held
+2 pts
From: Q7 · Core claim 🟡
Content-critical question only partially held
+2 pts
From: Q8 · Severity of the miss (overall human judgment) 🟡
Minor / cosmetic deviation
+1 pts
From: Q3 · Location of the main deviation 🟡
Minor / cosmetic deviation
+1 pts
From: Q4 · Cause of the deviation 🟡
Concordant (toward reproduced)
Code + data deposited & functional
-2 pts
From: Data & code availability Available & functional
Total score +4

Table 1 comparative genome statistics reproduce essentially 1:1 from the publicly deposited FASTAs — total length and contig counts exact for all 6 strains (wTex within 1 bp), barrnap rRNA=3 exact, Prokka CDS exact for 5/6, tRNA exact for all, GC differences fully explained by N-base handling. The only real deviation is the pseudogene column (reproduced 0 vs reported 2–55), which is on our methodology side — plain Prokka has no pseudogene caller while the paper used NCBI PGAP — not an authors' defect or fabrication. The reported values are derivable from the shared data (q5 green), but the paper's actual thesis (HGT functional enrichment, early-branching phylogeny) was out of scope, so the core claim is only partially confirmed (q7 yellow). Overall a solid reproduction with explainable deviations.

🤝
Reproduced automatically — and fairly

Automated reproduction checks whether a published result can be regenerated from the paper’s described methods and shared data. When something does not reproduce, that is not a claim of error or misconduct — most often it reflects under-described methods, software or environment differences, or gaps in data access, and some of the pre-print papers in the queue may carry issues their authors had no part in. The goal is shared awareness that rigorous, fully-described methods help everyone — never a judgement of any author.

Are you an author? We would genuinely like to hear from you — to clarify the record, add data or code, re-run the pipeline after an accession update, and publish your response right next to the assessment. Everything here is open and auditable.

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Reproduction footprint

claude-opus-4-8

Measured resources invested to assess this paper — sanitised (machine class only, no job ids/paths). Compute = HPC accounting (SLURM); tokens = the AI agent's session.

377.7 k
tokens (I/O) · 29.7 M incl. cache
68 min
runtime · 0.35 CPU-h
1.9 GB
peak RAM
2
HPC jobs
hummel
machine