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scSSL-Bench: Benchmarking Self-Supervised Learning for Single-Cell Data
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Benchmarks nineteen SSL methods (generic, single-cell-specific, foundation models, baselines) and augmentation/architecture choices on nine single-cell datasets across batch correction, cell type annotation, and missing modality prediction.
Problem
There is no systematic comparison of SSL methods, hyperparameters, augmentations, and design choices for single-cell genomics data, and unclear whether specialized single-cell methods beat generic SSL.
Approach
A standardized benchmark that adapts generic image/text SSL methods to scRNA-seq and CITE-seq data, compares them with single-cell-specific contrastive and generative methods and foundation models, and systematically ablates augmentations (CLEAR, CLAIRE-style MNN, new BBKNN), embedding and projector size, temperature, DSBN, and multi-modal integration.
Key results
- scVI is the best scRNA-seq batch-correction method, with CLAIRE second; finetuned scGPT is strong on Immune Cell Atlas (total 0.781 vs VICReg 0.644).
- On multi-modal BMMC, SimCLR achieves the top total batch-correction score of 0.767, and totalVI scores 0.562.
- Random masking is the most effective augmentation alone and in combination, and embedding dimensions of 64 or 128 perform best; retaining the projector and DSBN do not improve results.
Measured effects reported in the paper
| What was changed | Where | Measured | Effect |
|---|---|---|---|
| Use specialized single-cell methods rather than generic SSL for uni-modal batch correction | scRNA-seq batch correction · PBMC, Pancreas, and Immune Cell Atlas | Total | Mixed |
| Use generic methods such as SimCLR or VICReg rather than specialized methods | multi-modal batch correction · PBMC-M and BMMC | Total | Helped |
| Use generic SSL rather than specialized contrastive methods | cell type annotation · single-modal scRNA-seq datasets | Macro F1 | Helped |
| Finetune scGPT rather than use it zero-shot | scGPT · Immune Cell Atlas (10X 5' v2) | Macro F1: 0.358 -> 0.835 | Helped |
| Use random masking instead of other tested augmentations (ablation) | VICReg, SimCLR, and MoCo · batch correction datasets | Total | Helped |
| Use moderate embedding dimensionality (64 or 128) rather than lower dimensions (ablation) | generic SSL methods · HIC and MCA | Total | Helped |
| Increase embedding dimensionality (ablation) | generic SSL methods · HIC and MCA | biological conservation | Helped |
| Increase temperature (ablation) | SimCLR, MoCo, and NNCLR · HIC and MCA | batch correction | Hurt |
| Increase temperature (ablation) | SimCLR and NNCLR · PBMC-M | batch correction | Helped |
| Increase projector scaling factor (ablation) | Barlow Twins, BYOL, and VICReg · projector dimensionality ablation | performance | Helped |
| Retain the projector during inference (ablation) | SimCLR · MCA | Total: 0.625 -> 0.608 | Hurt |
| Apply domain-specific batch normalization instead of standard batch normalization (ablation) | generic SSL methods · HIC and MCA | Total | Hurt |
Surprising findings
- Generic SSL methods such as VICReg and SimCLR outperform specialized single-cell SSL frameworks on multi-modal integration and missing modality prediction.
- Retaining the projector during inference and domain-specific batch normalization, both recommended in prior work, do not improve and often reduce performance.
Limitations
- Multi-modal specialized methods (Concerto, scCLIP, scTEL) underperform, possibly due to limited tuning or implementation; results depend on specific preprocessing (4,000 HVGs)
- Hyperparameter tuning done on only two datasets (HIC and MCA)
- Concerto's DSBN not applied since public code lacks it
Experimental setup
Datasets: PBMC Pancreas Immune Cell Atlas Mouse Cell Atlas Human Immune Cells Lung Tabula Sapiens PBMC-M BMMC
Benchmarks: PBMC Pancreas Immune Cell Atlas PBMC-M BMMC MCA HIC Lung Tabula Sapiens
Metrics: scIB bio conservation scIB batch correction total score macro F1 accuracy Pearson correlation
Baselines: PCA SCDC scVI totalVI scGPT Geneformer scButterfly scTEL scCLIP
Builds on: SimCLR VICReg CLEAR CLAIRE Concerto scVI
Closest papers by meaning
- A Simple and Comprehensive Benchmark for Single-Cell Transcriptomics (AAAI 2025 · similarity 0.86)
- scPilot: Large Language Model Reasoning Toward Automated Single-Cell Analysis and Discovery (NeurIPS 2025 · similarity 0.85)
- Semi-supervised Knowledge Transfer Across Multi-omic Single-cell Data (NeurIPS 2024 · similarity 0.85)
- LangCell: Language-Cell Pre-training for Cell Identity Understanding (ICML 2024 · similarity 0.84)
- scMBERT: A Pre-Trained Deep Learning Model for Single-Cell Multiomic Data Representation and Prediction (Student Abstract) (AAAI 2025 · similarity 0.84)
- CellPLM: Pre-training of Cell Language Model Beyond Single Cells (ICLR 2024 · similarity 0.83)
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