scMUSCL: multi-source transfer learning for clustering scRNA-seq data
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.007 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.004 | 0.003 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.005 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".