VCBench

VCBench is a capability-stratified benchmark for single-cell foundation models, evaluating five models against pre-registered baselines across five dimensions.

First-time visitors — start here. The v1.0.0 release reconciles VCBench's evaluator with upstream cell-eval to numerical precision via an explicit anchor-convention parameter. The Arc State checkpoint lives publicly at huggingface.co/appliedscientific/arc-state-norman-gears-corrected — with paste-able reproduction snippets that recover the headline numbers in <5 min on CPU.

What it produces

The headline result is a 5-model × 5-dimension capability matrix scored against pre-registered trivial and strongest non-FM baselines, plus three reusable methodological tools that work independently of the specific models evaluated here.

Model	A: PRR	B: MacroF1 (native)	C: AUROC	C: AUPRC	C: EPR	D: Pearson	E: τ-b
Geneformer V2-316M	0.627 (FT+D)	0.181 (ZS)	0.626 (IE)	0.001 (IE)	0.000 (IE)	0.001 (ZS+D)	-0.017 (ZS)
scGPT (fine-tuned)	0.503 (FT)	0.012 (ZS)	0.519 (IE)	0.003 (IE)	20.05 (IE)	0.064 (ZS+D)	-0.057 (ZS)
UCE 33-layer	N/A	0.027 (ZS)	N/A	N/A	N/A	0.132 (ZS+D)	0.136 (ZS)
TranscriptFormer	-0.174 (ZS+D)	0.156 (ZS)	N/A	N/A	N/A	0.232 (ZS+D)	0.046 †
Arc State	0.402 (FT) ‡	N/A	N/A	N/A	N/A	DNR	DNR
Baselines
Additive (Ahlmann-Eltze)	0.890	—	—	—	—	—	—
Mean-prediction	0.579	—	—	—	—	0.152	—
No-change	0.000	—	—	—	—	—	—
PCA + kNN	—	0.166	—	—	—	—	—
Co-expression	—	—	0.558	0.004	15.50	—	—
pySCENIC	—	—	0.501	0.0011	3.50	—	—
scLinear	—	—	—	—	—	0.129	—
Mean-celltype	—	—	—	—	—	0.152	—
PCA + DPT	—	—	—	—	—	—	0.190

† TranscriptFormer Dim E = unweighted mean of sci-fate (0.051) and Weinreb (0.041 ± 0.078); the Weinreb component is itself a bootstrap mean over 10 random 5K-cell subsamples (ARPACK non-convergence on the full 49K-cell graph). ‡ Arc State Norman evaluated on the disjoint GEARS train/test split (seed=1); PRR = 0.402, VC Level 1.

VC Level outcomes (binding scoring uses the common-label-set protocol on Dim B):

• Geneformer V2-316M, scGPT, UCE, Arc State → Level 1 (clears trivial baseline on at least one dim)
• TranscriptFormer → Level 2 (clears mean-celltype on Dim D: 0.232 > 0.152)
• No model achieves Level 3.

How to run it

git clone https://github.com/AppliedScientific/VCBench.git
cd VCBench
git checkout v1.0.0 # pin to the release tag
pip install -e .
make tests # full test suite (unit + integration + correctness), ~3s, no GPU needed
make all # full reproduction from cached HF embeddings (CPU-OK)

The three reusable methodological tools work independently of make all:

fromvcbench.protocolsimportcommon_label_set# Eq. 5fromvcbench.probesimportspread_error_correlation# Eq. 10fromvcbench.contaminationimportContaminationManifest, validate_manifest

Hardware

Stage	CPU?	Wall-clock on H200
Cached-embedding reproduction (make all)	✅	~30 min on a Mac
Baselines (additive, PCA+kNN, co-expression, mean-celltype, PCA+DPT)	✅	~1 h CPU
FM fine-tuning (Geneformer 5.7h + scGPT 2.75h + Arc State ~3h)	GPU	~12 h
FM embedding extraction at scale (TranscriptFormer Dim B)	GPU	~2 h
Total fresh reproduction (make fresh)	GPU	~18 h H200

Where next

• Install paths:INSTALL.md (Docker / conda / pip)
• Reusable methodological tools: the vcbench.protocols / vcbench.probes / vcbench.contamination packages each have full numpy-style docstrings + worked examples
• Manuscript ↔ code traceability: every Eq. (1–9) of VCBench (2026) is implemented in src/vcbench/dimensions/dim_*/metrics.py with the equation number and reference values in the module docstring
• Reference-value drift detection:tests/reference_values.json locks every §I.4 capability-matrix cell; tests/unit/ contains drift detectors that fire if the on-disk JSONs / CSVs ever diverge

Note on the two src/ trees

The repository carries two source trees:

• src/vcbench/ — the canonical Python package, pip install -e .-able. This is what model developers and downstream tooling import from. It owns the three reusable methodological tools, the per-dimension evaluation modules, the FoundationModel ABC + per-model wrappers (incl. Arc State), the python -m vcbench CLI, the contamination schema, and the test suite.
• src/{baselines,data,evaluation,models,utils}/ — the legacy pipeline tree that produced the on-disk reference artefacts (results/dim_*/, results/baselines/, etc.). Its step1–stepN runtime functions are the verified path that produced every §I.4 reference value. The new vcbench.models.* wrappers compose these step* functions in their run_dim_a() orchestration so end-to-end execution still flows through proven code while the public ABI lives in the new package.

Import only from vcbench.*; treat src.{baselines,data,evaluation,models,utils}.* as internal implementation detail.

Artifacts & reproducibility

Per-dimension reference outputs live under results/; the published supplementary tables are in tables/.

Trained model checkpoints and embedding tensors are archived on HuggingFace Hub — see docs/MANIFEST.md for the file-by-file index. Three HF repos:

Repo	Type	Contents
arc-state-norman-gears-corrected	model	Arc State checkpoint + eval CSVs + training config
vcbench-geneformer-perturbation	model	Geneformer V2-316M fine-tuned classifier
vcbench-embeddings	dataset	Cell/gene embeddings across Dim A–E

All three repos are publicly available on HuggingFace.

fromhuggingface_hubimportsnapshot_downloadsnapshot_download("appliedscientific/arc-state-norman-gears-corrected", repo_type="model")
snapshot_download("appliedscientific/vcbench-geneformer-perturbation", repo_type="model")
snapshot_download("appliedscientific/vcbench-embeddings", repo_type="dataset")

Environments

3 GPU environments grouped by compatible PyTorch versions, plus 2 CPU environments:

Environment	Python	PyTorch	Models
vcbench-analysis	3.10	-	Baselines, evaluation, probes, assembly
vcbench-scenic	3.8	-	pySCENIC (dependency conflicts)
vcbench-pt118	3.10	CUDA 11.8	Geneformer, UCE
vcbench-pt212	3.9	2.1.2	scGPT
vcbench-pt25	3.11	<=2.5.1	TranscriptFormer, State

Models

Model	Dim A	Dim B	Dim C	Dim D	Dim E	Environment
Geneformer V2-316M	Embedding shift + decoder	Ortholog remap + embed	Attention layer 13	Embedding probe	DPT probe	vcbench-pt118
scGPT (fine-tuned)	Fine-tune + predict	Ortholog remap + embed	Gene embedding similarity	Embedding probe	DPT probe	vcbench-pt212
UCE 33-layer	N/A	Native cross-species	N/A	Embedding probe	DPT probe	vcbench-pt118
TranscriptFormer	Autoregressive generation	Native cross-species	Gene prompting	Embedding probe	DPT probe	vcbench-pt25
Arc State	Train from scratch	N/A	N/A	Embedding probe	DPT probe	vcbench-pt25

Metrics

Dimension	Metrics	Baselines
A: Perturbation	PRR (Pearson R on Δ-expression), DES, MAE, Composite	Additive, Mean, No-change
B: Cross-Species	Macro F1, Weighted F1	PCA + kNN
C: GRN	AUROC, AUPRC, EPR	Co-expression, pySCENIC
D: Cross-Modal	Pearson R, RMSE	PCA + ridge, scLinear, Mean celltype
E: Temporal	Kendall tau, kNN balanced accuracy	PCA + DPT

Requirements

• RAM: 32-64 GB recommended
• Disk: 100 GB+ for raw datasets + model weights
• GPU: A100 80GB recommended (required for UCE; 40GB sufficient for others)
• Baseline construction: CPU-only, no GPU needed
• Estimated GPU time: ~75 GPU-hours total

License

VCBench is released under the MIT License.

Citation

If you use VCBench in your research, please cite both the preprint and the software release. Machine-readable metadata is in CITATION.cff.

Preprint — Weidener, L., Brkić, M., Jovanović, M., Ulgac, E., Meduri, A. VCBench: A Multi-Dimensional Benchmark for Single-Cell Foundation Models, Applied Scientific Intelligence, Inc. (2026). doi:10.64898/2026.06.18.733146

@article{weidener2026vcbench,
title = {VCBench: A Multi-Dimensional Benchmark for Single-Cell Foundation Models},
author = {Weidener, L. and Brkić, M. and Jovanović, M. and Ulgac, E. and Meduri, A.},
year = {2026},
doi = {10.64898/2026.06.18.733146},
url = {https://doi.org/10.64898/2026.06.18.733146},
note = {Preprint}
}