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Record W4407932243 · doi:10.1038/s41467-026-74171-0

Cluster replicability in single-cell and single-nucleus atlases of the mouse brain

2025· preprint· en· W4407932243 on OpenAlexaff
Leon French, Hamsini Suresh, Jesse Gillis

Bibliographic record

VenueNature Communications · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsUniversity of Toronto
FundersNational Institute of Mental Health
KeywordsBiologyComputational biologyCluster (spacecraft)RNATranscriptomeGeneGeneticsEvolutionary biologyNeuroscienceGene expressionComputer science

Abstract

fetched live from OpenAlex

Single-cell RNA sequencing has advanced our understanding of cellular heterogeneity. Ensuring the replicability of identified cell clusters across studies is essential for determining their biological robustness. We assess the replicability of cell clusters identified in two large mouse brain atlases, one generated using single-cell RNA sequencing and the other with single nuclei. Both profile over 4 million cells and group them into over 5000 clusters. Using transcriptome-wide neighbor voting, we identify 2009 reciprocally matched cluster pairs with consistent spatial localization and coordinated gene expression, which were also observed in datasets from multiple species. Reciprocal clusters are enriched in the cerebellum, where lower diversity aids replicability, while the hypothalamus's heterogeneity limits agreement. Distinguishing close clusters is much more challenging than differentiating a cluster from most others, especially when using marker genes. By incorporating replicability data, we provide a stronger foundation for investigating the newly identified clusters and their biological meaning.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.007
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: Reproducibility · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.998
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.007
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.272
Teacher spread0.250 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

Study designObservational
DomainReproducibility
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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