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scSSL-Bench: Benchmarking Self-Supervised Learning for Single-Cell Data

ICML 2025 · Label-efficient and robust learning › Self-supervised and contrastive · approach: Data-efficient and robust self-supervision · 0 citations (OpenAlex)

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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

Measured effects reported in the paper

What was changedWhereMeasuredEffect
Use specialized single-cell methods rather than generic SSL for uni-modal batch correctionscRNA-seq batch correction · PBMC, Pancreas, and Immune Cell AtlasTotalMixed
Use generic methods such as SimCLR or VICReg rather than specialized methodsmulti-modal batch correction · PBMC-M and BMMCTotalHelped
Use generic SSL rather than specialized contrastive methodscell type annotation · single-modal scRNA-seq datasetsMacro F1Helped
Finetune scGPT rather than use it zero-shotscGPT · Immune Cell Atlas (10X 5' v2)Macro F1: 0.358 -> 0.835Helped
Use random masking instead of other tested augmentations (ablation)VICReg, SimCLR, and MoCo · batch correction datasetsTotalHelped
Use moderate embedding dimensionality (64 or 128) rather than lower dimensions (ablation)generic SSL methods · HIC and MCATotalHelped
Increase embedding dimensionality (ablation)generic SSL methods · HIC and MCAbiological conservationHelped
Increase temperature (ablation)SimCLR, MoCo, and NNCLR · HIC and MCAbatch correctionHurt
Increase temperature (ablation)SimCLR and NNCLR · PBMC-Mbatch correctionHelped
Increase projector scaling factor (ablation)Barlow Twins, BYOL, and VICReg · projector dimensionality ablationperformanceHelped
Retain the projector during inference (ablation)SimCLR · MCATotal: 0.625 -> 0.608Hurt
Apply domain-specific batch normalization instead of standard batch normalization (ablation)generic SSL methods · HIC and MCATotalHurt

Surprising findings

Limitations

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

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