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scMUSCL: multi-source transfer learning for clustering scRNA-seq data

2025· article· en· W4408956502 on OpenAlexafffund
Arash Khoeini, Funda Sar, Yen‐Yi Lin, Colin C. Collins, Martin Ester

Bibliographic record

VenueBioinformatics · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsUniversity of British ColumbiaSimon Fraser University
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsTransfer of learningCluster analysisComputer scienceTransfer (computing)Data sourceArtificial intelligenceData miningParallel computing

Abstract

fetched live from OpenAlex

MOTIVATION: Single-cell RNA sequencing (scRNA-seq) analysis relies heavily on effective clustering to facilitate numerous downstream applications. Although several machine learning methods have been developed to enhance single-cell clustering, most are fully unsupervised and overlook the rich repository of annotated datasets available from previous single-cell experiments. Since cells are inherently high-dimensional entities, unsupervised clustering can often result in clusters that lack biological relevance. Leveraging annotated scRNA-seq datasets as a reference can significantly enhance clustering performance, enabling the identification of biologically meaningful clusters in target datasets. RESULTS: In this article, we propose Single Cell MUlti-Source CLustering (scMUSCL), a novel transfer learning method designed to identify cell clusters in a target dataset by leveraging knowledge from multiple annotated reference datasets. scMUSCL employs a deep neural network to extract domain- and batch-invariant cell representations, effectively addressing discrepancies across various source datasets and between source and target datasets within the new representation space. Unlike existing methods, scMUSCL does not require prior knowledge of the number of clusters in the target dataset and eliminates the need for batch correction between source and target datasets. We conduct extensive experiments using 20 real-life datasets, demonstrating that scMUSCL consistently outperforms existing unsupervised and transfer learning-based methods. Furthermore, our experiments show that scMUSCL benefits from multiple source datasets as learning references and accurately estimates the number of clusters. AVAILABILITY AND IMPLEMENTATION: The Python implementation of scMUSCL is available at https://github.com/arashkhoeini/scMUSCL.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: none
Teacher disagreement score0.833
Threshold uncertainty score0.646

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.042
GPT teacher head0.280
Teacher spread0.238 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreMethods

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

Citations2
Published2025
Admission routes2
Has abstractyes

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