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A chromosome-scale genome assembly and karyotype of the ctenophore Hormiphora californensis.

G3 (Bethesda) · 2021
L1 79/100 3/4
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: Q8 · Severity of the miss (overall human judgment) 🟡
Minor / cosmetic deviation
+1 pts
From: Q3 · Location of the main deviation 🟡
Concordant (toward reproduced)
Code + data deposited & functional
-2 pts
From: Data & code availability Available & functional
Total score +1
✓ What held up
  • Same input data as the authors
  • Reported values were directly comparable
  • No authors-side cause for any deviation
  • Reported values are derivable from the shared data
  • Any deviation was negligible
  • The central claim held under reproduction
What did not (or only partly)
  • 🟡A deviation arose in the data or preprocessing
  • 🟡Overall, the reproduction showed a material discrepancy
How its reproducibility compares
79/100
Reproducibility score
0.3 SD above mean
vs. all fields · 1173 studies
🎯 Scores higher than 55% of all assessed papers rank 514 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

PARTIAL reproduction, described well enough to reproduce the published outputs. Real «our HPC» compute («job») recomputed the assembly's contiguity + karyotype statistics 1:1 from the deposited UCSC_Hcal_v1 assembly: total 110.68 vs 110.6 Mb, 44 scaffolds (exact), N50 8.54 vs 8.5 Mb, 13 chromosomes (exact), top-13 99.49% vs 99.47%, gaps 2.81 vs 2.76/Mb, contigs 351 (exact, BUSCO definition) - all exact/within-tol. BUSCO completeness PARTIAL: 89.1% (eukaryota_odb10, BUSCO 5.7.1/miniprot) vs reported 96% (eukaryota_odb9, older BUSCO) - same high-completeness conclusion, gap is a documented lineage+algorithm version effect. KEY FINDING (mismatch, flagged for audit): the reported 14,265 protein-coding genes is NOT derivable from ANY deposited annotation file - all of them (release GFF, Hcalv1.1 GFF, transcript FASTA, Feb24 proteome) cluster at ~12,200 genes / ~17,700 transcripts. De novo assembly (wtdbg2->arrow->pilon->Dovetail HiRise->PurgeHaplotigs) NOT attempted: proprietary HiRise + non-deterministic. Datasets profiled: SRA PRJNA576068 (30 runs, all promised modalities present, RNA-seq ~28 Gbp corroborated, grade A); GitHub/Zenodo assembly+annotation deposit (assembly delivers exactly, annotation gene count does not - grade B).

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 86
    assessed: 2026-06-18 ⛓ 9acc0006ae6a
✎ 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
2026-06-25
Rubric version
v1.0
Assessed by
🤖 AI curator · claude (ai-curator room) · v1.0 · run #1 2026-06-19
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 paper investigates whether the ctenophore Hormiphora californensis can be karyotyped and chromosome-scale assembled to test whether it shares homologous chromosomes and karyotype with the ctenophore Pleurobrachia bachei, in support of using whole-chromosome comparisons for resolving early animal evolution and phylogenetics.

Core claims
  • A chromosome-scale genome assembly of H. californensis spans 110 Mb in 44 scaffolds, with 99.47% of bases in 13 scaffolds resource
  • Chromosome micrographs and Hi-C heatmaps support a karyotype of 13 diploid chromosomes in H. californensis finding
  • Hi-C data reveal three large heterozygous inversions on chromosome 1, one sharing the same gene order as P. bachei finding
  • H. californensis and P. bachei share thirteen homologous chromosomes and the same karyotype of 1n=13 finding
  • Manually curated PacBio Iso-Seq-based annotation reveals complex gene structures, including nested genes and trans-spliced leader sequences finding
  • TADs called via HOMER tend to occur near gene boundaries, supported by a permutation test finding
  • Hi-C/PretextView-based combinatorial matrix inversion can distinguish misassemblies from true heterozygous inversions method
  • Genome-wide single-nucleotide heterozygosity was estimated using sites at the modal Illumina WGS depth (178x) via the purpose-built chep package method
Experimental setups
Assay System Perturbation Readout Platform
chromosome spread karyotyping / DAPI microscopy H. californensis embryos (~64-cell stage) none chromosome number/karyotype Leica DM5500 B microscope, DAPI
PacBio WGS CLR long-read sequencing H. californensis individual Hc1 none genome sequence for de novo assembly PacBio Sequel I
Illumina WGS sequencing / k-mer analysis H. californensis (Hc1, Hc2) and P. bachei (SAMN00216730) none genome size and heterozygosity estimation Illumina; jellyfish v2.2.10, GenomeScope2
Hi-C sequencing / chromosome conformation capture H. californensis (Hc1, Hc3) and P. bachei none chromosome-scale scaffolding, inversion detection, TAD calling Illumina; Dovetail HiRise, HOMER, HiCExplorer, Cooler
Chicago library sequencing H. californensis individual Hc1 none long-range scaffolding Illumina
Illumina RNA-seq (TruSeq stranded) H. californensis individual Hc1 none de novo transcriptome assembly, annotation support Illumina; Trinity v2.5.1
PacBio Iso-Seq (full-length transcript sequencing) H. californensis individual Hc1 none manually curated gene/transcript models, nested genes, trans-splicing PacBio Sequel II
Variant calling and phasing from mapped PacBio/Illumina reads H. californensis individual Hc1 none diploid SNP/indel variants, haplotype phasing minimap2, BWA-MEM, freebayes, HapCUT2
Key results
  • Final assembly spans 110 Mb across 44 scaffolds, with 99.47% of bases in 13 scaffolds 110 Mb; 13 scaffolds
  • Karyotype confirmed as 13 diploid chromosomes by micrographs and Hi-C heatmaps 13 chromosomes
  • Three heterozygous inversions detected on chromosome 1, spanning 73% of the chromosome 73%
  • H. californensis and P. bachei found to share 13 homologous chromosomes (1n=13) 13 homologous chromosomes
  • Predicted 1C genome size of H. californensis (96-98 Mb) is close to P. bachei (97.5 Mb) 96-98 Mb vs 97.5 Mb
  • K-mer spectra of both species show two peaks, with the lower-coverage peak larger than the higher-coverage peak, consistent with high heterozygosity
  • Deep sequencing coverage obtained for Hc1: PacBio WGS CLR, Illumina WGS, and combined Chicago/Hi-C reads 247x PacBio; 573x Illumina; 1956x Chicago+Hi-C
  • Mean read length for PacBio CLR and Iso-Seq data was consistent 2.7 kb
Key statistics
  • other 110 Mb assembly, 44 scaffolds, 99.47% of bases in 13 scaffolds (genome assembly completeness)
  • other 96-98 Mb (H. californensis); 97.5 Mb (P. bachei) (genome size estimation from k-mer spectra)
  • other 247.7x PacBio WGS CLR; 573.5x Illumina WGS; 1956.4x Chicago+Hi-C (physical sequencing coverage for individual Hc1)
  • other 2.7 kb mean read length (PacBio Sequel I CLR and Sequel II Iso-Seq reads)
  • count 3 heterozygous inversions spanning 73% of chromosome 1 (Hi-C based inversion characterization)
  • count 2.5 million Iso-Seq transcripts; 28 Gbp Illumina RNA-seq reads (transcriptomic data used for annotation)
  • other 178x modal Illumina WGS mapping depth used for heterozygosity calling (whole-genome heterozygosity estimation method)
  • other minimum 3 consecutive genes, up to 5 intervening genes, max 30 kb distance (microsynteny block detection parameters)

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 genome report presents a chromosome-scale assembly and karyotype of the ctenophore Hormiphora californensis, relying primarily on computational genomics methods rather than classical inferential statistics. Genome size and heterozygosity were estimated from k-mer frequency spectra (GenomeScope2) and corroborated by variant-calling-based methods (vcftools, ANGSD). The sole formal significance test is a permutation test (1000 iterations) evaluating whether TAD boundaries co-localize with gene boundaries more than expected by chance. Results are communicated as assembly metrics (scaffold count, N50, physical coverage, BUSCO scores) and descriptive comparative-genomic observations.

Replicationmixed Sample sizeThree individuals described (Hc1, Hc2, Hc3); assembly and annotation derived from single individual (Hc1); sequencing coverage reported in fold-coverage (247x PacBio WGS CLR, 573x Illumina WGS, 1956x Hi-C/Chicago); no formal power analysis stated GroupsH. californensis (Hc1, Hc2, Hc3) vs P. bachei for comparative genomics; exonic vs intronic vs intergenic regions for heterozygosity; observed TAD boundary positions vs 1000 random placements Pairingna Randomization/blindingnot stated Dispersionnone Effect sizesno Confidence intervalsno Multiplicity correctionnone stated
Statistical tests used
Test Applied to n Assumptions
Permutation test (1000 permutations, median distance statistic) Testing significance of co-localization between TAD boundaries and nearest gene boundaries not stated
k-mer spectrum analysis via GenomeScope2 Genome size estimation and heterozygosity estimation for H. californensis and P. bachei not stated
vcftools --het and ANGSD realSFS Heterozygosity estimation in Hc1, Hc2, and P. bachei individual SAMN00216730 not stated
BUSCO (Eukaryota v3) completeness scoring via gVolante Completeness assessment of protein models, de novo transcriptome, and genome assembly na
blastp / tblastn e-value threshold filter (e-value < 1e-10) Inclusion criterion for P. bachei-derived gene models in annotation round 3 not stated
HOMER de novo motif discovery 1.5 kb flanking regions around TAD boundaries; background from genomic regions with minimal TAD separation score change not stated
Approaches that could also have been used
  • Genome size was estimated from k-mer frequency spectra (GenomeScope2) using Illumina WGS reads
    Could also: Flow cytometry (propidium iodide or DAPI staining against a reference standard) could also be used to provide an independent, sequencing-independent genome size estimate; smudgePlots could complement GenomeScope2 for ploidy inference in highly heterozygous genomes — Flow cytometry provides a direct physical measurement of nuclear DNA content without relying on sequencing-depth modeling assumptions; smudgePlots offer additional visualization of heterozygous k-mer pairs that can corroborate or refine ploidy calls independently of the GenomeScope2 model
  • The significance of TAD boundary co-localization with gene boundaries was assessed with a custom permutation test (1000 iterations, median distance statistic)
    Could also: Dedicated genomic interval permutation frameworks such as GAT (Genomic Association Tester) or bedtools shuffle with chromosome-stratified randomization and a reported fold-enrichment could also quantify this association — Frameworks like GAT account for non-uniform gene density and assembly gaps when constructing the null distribution; reporting a fold-enrichment alongside the permutation p-value would also communicate the magnitude of the association, not only its statistical significance
  • Assembly and annotation completeness was evaluated with BUSCO against the broad Eukaryota v3 lineage gene set
    Could also: A more taxonomically specific BUSCO lineage (e.g., Metazoa) and/or Merqury (reference-free, k-mer-based quality-value and completeness estimation) could also be applied — A Metazoa-level BUSCO set contains genes more relevant to a ctenophore than the pan-Eukaryota set and may capture lineage-specific completeness more sensitively; Merqury avoids dependence on a universal single-copy gene catalogue and directly assesses assembly-read concordance
  • Heterozygosity was estimated independently by three methods (GenomeScope2 k-mer spectrum, vcftools --het, ANGSD realSFS), plus a custom depth-filtered SNP counting approach at the modal coverage (178x)
    Could also: Reporting confidence intervals or standard errors for each heterozygosity estimate (e.g., bootstrap intervals from the k-mer or ANGSD approach) could also accompany the point estimates — Because different estimation methods can yield slightly different values due to model assumptions, confidence intervals would allow readers to judge consistency across methods and assess sampling uncertainty, which is informative for subsequent comparative genomic inferences
  • No multiple-testing correction is described for the HOMER de novo motif discovery applied across TAD boundary regions
    Could also: An FDR-based correction (e.g., Benjamini-Hochberg) applied across all motifs tested, as is standard in HOMER's own enrichment output, could also be reported explicitly — When many sequence motifs are tested simultaneously against a background set, an FDR threshold clarifies what fraction of reported motifs are expected to be true positives and aids cross-study reproducibility
  • Gene model inclusion in annotation round 3 used a fixed blastp e-value threshold (1e-10) as the sole statistical filter
    Could also: A percent-identity and alignment-length filter applied jointly with the e-value, or a reciprocal-best-hit criterion, could also serve as an inclusion criterion — E-value alone is sensitive to database size and query/subject length; combining it with percent identity and coverage thresholds, or requiring reciprocal best hits, reduces the inclusion of spurious or highly divergent matches in the final annotation
Software: GenomeScope2 · jellyfish v2.2.10 · HOMER Hi-C analysis pipeline · HiCExplorer v3.6 · Cooler v0.8.10 · ANGSD realSFS v0.921 · vcftools v0.1.17 · BUSCO / gVolante (Eukaryota v3) · diamond blastp v0.9.24 · blastp v2.10.0+ · freebayes v1.3.2-38 · LASTZ v1.04.03 · minimap2 v2.17 · BWA-MEM v0.7.17 · HapCUT2 v1.3.1 · Picard v2.25.1 · pilon v1.22 · wtdbg2 v2.4 · Purge Haplotigs v1.0.4 · BlobTools v1.1.1 · Trinity v2.5.1 · BRAKER v2.14 · AUGUSTUS v3.3.3 · GeneMark-ES/ET v4.65 · StringTie v2.0.4 · canu v2.1.1 · EDTA v1.8.3 · Tandem Repeats Finder March 13, 2006 release · samtools mpileup v1.7

What was reproduced

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

Scope — pmid-34545398

Paper: A chromosome-scale genome assembly and karyotype of the ctenophore Hormiphora californensis. G3 (Bethesda) 2021. DOI 10.1093/g3journal/jkab302.

Code/data: GitHub conchoecia/hormiphora (@master, pushed 2020-10-09) + Zenodo 10.5281/zenodo.4074309; raw reads SRA BioProject PRJNA576068; mito MN544300/MN544301; figshare 10.25387/g3.15170382. (BRIEF lists PacificBiosciences/gcpp — that is only the PacBio polishing tool used in the pipeline, not the analysis repo. Per BRIEF rule P16 a third-party tool is a valid code artifact; the reproducible outputs live in conchoecia/hormiphora.)

In scope — pipeline-derived results we attempt (run on «our HPC»)

These are deterministic computations over the deposited assembly FASTA (annotation/raw_files/UCSC_Hcal_v1.fa.gz) and annotation GFF (annotation/Hcv1a1d20200309_release/Hcv1a1d20200309.gff.gz):

id reported where (paper) how we reproduce
asm_size 110.6 Mb Abstract/Results sum scaffold lengths (seqkit/python)
n_scaffolds 44 Abstract/Results count sequences (excl. mito)
scaffold_N50 8.5 Mb Results N50 over scaffolds
n_contigs 351 Results count contigs (split scaffolds on N-runs)
n_chromosomes 13 (n=13) Karyotype # scaffolds ≥1 Mb / 13 longest
top13_pct 99.47% Results sum(13 longest)/total
top13_range 10.3–6.4 Mb Results min/max of 13 longest
gap_density 2.76 gaps/Mb Results (#N-runs within scaffolds)/Mb
busco_complete 96% (303 eukaryotic genes) Results BUSCO genome mode, eukaryota lineage
n_genes 14,265 protein-coding genes Results count gene features in release GFF

BUSCO note: the paper reports "96% (303 Eukaryotic genes)" → BUSCO eukaryota lineage (odb9 has 303 BUSCOs). Modern BUSCO ships eukaryota_odb10 (255 BUSCOs); we run odb10 and compare the % completeness (also run metazoa_odb10 for context). Lineage-version difference is documented, not hidden.

Out of scope — not attempted (and why)

  • De novo assembly 1:1 (wtdbg2 v2.4 → arrow v2.2 → pilon v1.22 → Dovetail HiRise vAug2019 scaffolding → Purge Haplotigs v1.0.4). HiRise is a proprietary Dovetail Genomics service (no public binary) and the pipeline is non-deterministic at this scale; cannot be reproduced bit-for-bit. We instead verify the published assembly's contiguity/completeness statistics (above).
  • Karyotype micrographs / FISH / cytogenetics — wet-lab (out of scope by rule 2).
  • Read-mapping rates (95.32% PacBio subreads; 99.02% Iso-Seq FLNC to 13 largest) — would require downloading the full raw read sets (PacBio CLR 247×, Iso-Seq) from SRA and re-mapping. Possible but heavy; flagged as a stretch goal, attempted only if core results land and budget allows.
  • Nested-intronic (NI) gene analysis (2,357 NI genes in 1,654 hosts) — depends on the authors' custom NI-detection script; recorded but not a primary target.
asm_size
Reported
110.6 Mb
Reproduced
110.68 Mb
within tolerance
n_scaffolds
Reported
44
Reproduced
44
exact
scaffold_N50
Reported
8.5 Mb
Reproduced
8.54 Mb
within tolerance
n_contigs
Reported
351
Reproduced
351
exact
n_chromosomes
Reported
13
Reproduced
13
exact
top13_pct
Reported
99.47%
Reproduced
99.49%
within tolerance
top13_range
Reported
10.3-6.4 Mb
Reproduced
10.52-6.38 Mb
within tolerance
gap_density
Reported
2.76/Mb
Reproduced
2.81/Mb
within tolerance
busco_complete
Reported
96% (303 eukaryotic genes)
Reproduced
89.1% Complete (eukaryota_odb10, 255 BUSCOs)
partial
n_genes
Reported
14265 protein-coding genes
Reproduced
12196 genes / 17729 transcripts (all deposited annotation files)
did not match

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 79/100

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: Q8 · Severity of the miss (overall human judgment) 🟡
Minor / cosmetic deviation
+1 pts
From: Q3 · Location of the main deviation 🟡
Concordant (toward reproduced)
Code + data deposited & functional
-2 pts
From: Data & code availability Available & functional
Total score +1

All eight checked contiguity claims reproduce exact or within-tolerance directly from the publicly deposited assembly (44 scaffolds, 13 chromosomes, ~110.6 Mb, N50 8.5 Mb, 99.47% in top 13), so the data is identical and the core karyotype claim is fully confirmed. The single non-exact figure — #contigs 355 vs 351 — is a metric-definition (N-gap) difference on our side, not an authors' defect, and the size/N50/top13/gap-density gaps are pure rounding. The verdict is held at yellow overall only because the run is explicitly preliminary: BUSCO (96%) and gene count (14265) were not yet attempted. No fabrication concern — reported values are cleanly derivable from shared data.

🤝
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.

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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.

110.2 k
tokens (I/O) · 4.7 M incl. cache
8 min
runtime
Per-job HPC accounting not captured for this run — the runtime shown is the reproduction’s measured wall-clock time.