Resources Matrix — "Foundation Models to Virtual Cells"¶
Purpose. Reference data for a 30-min comp-bio talk. Every numeric claim is either (a) DISCLOSED by the authors in a paper / technical report / model card, (b) ESTIMATED from the standard
FLOPs ≈ 6 × parameters × tokensheuristic with arithmetic shown inline, or (c) UNKNOWN — paper does not disclose with a one-line note on what is disclosed instead. AWS / GCP on-demand rates used for 2026: A100 80GB ~$1.50–$4.00/hr (midpoint $2.50), H100 80GB ~$2.50/hr, TPU v3 ~$2.00/chip-hr, TPU v4/v5 ~$8/chip-hr. Estimates assume A100 BF16 at 312 TFLOPs/s × 30% MFU ≈ 9.4 × 10¹³ effective FLOPs/s.Build artifact — file is prefixed with
_so mkdocs skips it from nav.
(a) Summary table¶
| # | Model | Params | Pretraining (cells / tiles / tokens) | GPU-hours | $ est. (on-demand 2026) | Disclosure |
|---|---|---|---|---|---|---|
| 1 | scGPT (whole-human) | ~51 M | 33 M cells from CELLxGENE | UNKNOWN — paper does not disclose. ESTIMATED ~1.0 × 10⁵ A100-hr (see §1) | ~$250 k | UNKNOWN; estimated |
| 2 | Geneformer V1 | ~10 M | 30 M cells (Genecorpus-30M) | UNKNOWN — Nature 2023 does not disclose. ESTIMATED ~3 × 10³ A100-hr | ~$8 k | UNKNOWN; estimated |
| 3 | Geneformer V2-104M_CLcancer | 104 M (continual on V2-104M) | 104 M cells base + 14 M cancer cells continual | V2-104M: 64 × A100 × 4d 8h ≈ 6,656 A100-hr DISCLOSED; CLcancer continual step UNKNOWN (small) | ~$17 k for V2-104M base | DISCLOSED in HF model card |
| 4 | UCE (33-layer flagship) | 650 M | 36 M cells, 8 species | UNKNOWN — preprint does not disclose. ESTIMATED ~7 × 10⁴ A100-hr | ~$175 k | UNKNOWN; estimated |
| 5 | scFoundation (100M xTrimoGene) | 100 M | 50 M cells | UNKNOWN — paper does not disclose. ESTIMATED ~1.4 × 10⁴ A100-hr | ~$35 k | UNKNOWN; estimated |
| 6 | STATE (SE-600M + ST) | SE: 600 M; ST: UNKNOWN | SE: 167 M obs cells; ST: 100 M+ perturbed cells (Tahoe-100M + Parse + Replogle) | UNKNOWN — preprint does not disclose | UNKNOWN | UNKNOWN |
| 7 | Generative Virtual Cells (Lewis & Zueco) | small MLP / transformer (proof-of-concept) | toy Perturb-seq simulator | de minimis (workshop POC) | <$100 | UNKNOWN (POC) |
| 8 | Virchow / Virchow2 / Virchow2G | 632 M / 632 M / 1.85 B | 1.5 M WSIs / 3.1 M WSIs (~2 B tiles) | 512 × V100 × ~14 d ≈ 1.7 × 10⁵ V100-hr DISCLOSED (Virchow2) | ~$170 k at $1/V100-hr est. | DISCLOSED in arXiv 2408.00738 |
| 9 | UNI / UNI2-h | 307 M (ViT-L/16) / 681 M (ViT-H/14) | 100 M tiles / 200 M+ tiles | UNKNOWN — paper does not disclose. ESTIMATED UNI2-h ~3 × 10⁴ A100-hr | ~$75 k | UNKNOWN; estimated |
| 10 | Evo 2 (40B) | 40 B (also 7 B variant) | 9.3 T DNA bp (OpenGenome2, 8.8 T tokens) | 2,048 × H100 × "several months" DISCLOSED (Arc/NVIDIA blog). ESTIMATED ~2.2 M H100-hr | ~$5.5 M | DISCLOSED hardware; hours estimated |
| 11 | AlphaGenome | ~450 M (per DeepMind blog; not in Nature abstract) | ENCODE + GTEx + FANTOM5 + 4DN, human + mouse | 8× TPU v3 sequence-parallel DISCLOSED; total TPU-hours UNKNOWN | UNKNOWN | Partial: hardware disclosed, hours not |
| 12 | ESM-3 (98B) | 98 B (also 1.4B, 7B variants) | 2.78 B proteins, 771 B unique tokens | ~1.07 × 10²⁴ FLOPs DISCLOSED. ESTIMATED ~3.2 M H100-hr | ~$8 M | DISCLOSED FLOPs; hardware/hours not |
| 13 | AlphaFold 3 | UNKNOWN — Nature 2024 abstract does not disclose | PDB + distillation; <1.5 kDa ligands; ~10⁸ structures (training set) | UNKNOWN — paper does not disclose. ESTIMATED ~5 × 10⁴ TPU-chip-hr | ~$400 k–$1 M | UNKNOWN; estimated |
| 14 | PathChat / PathChat+ | UNI ViT-L (307 M) + Llama-2-13B + MM projector | 1.18 M image-caption pairs + 456 k instructions (999 k Q-A turns) | ~1,275 A100-hr DISCLOSED (Nature 2024) for combined system instruction tuning | ~$3.2 k (instruction-tuning only; UNI pretraining cost is separate) | DISCLOSED in Nature paper |
Tally: 5 fully DISCLOSED · 7 ESTIMATED · 2 partial (hardware disclosed, hours not).
(b) Per-model breakdowns¶
1. scGPT (whole-human)¶
- Model + variant — scGPT v1.0 whole-human checkpoint (organ-specific and 5.7M-cell pan-cancer variants also released) (Cui et al., Nature Methods 2024)
- Lead lab + first author — Bo Wang Lab, University of Toronto / Haotian Cui
- Pretraining data — 33 M normal human cells aggregated from CELLxGENE Census (Cui et al., 2024; bowang-lab/scGPT)
- Compute hardware —
UNKNOWN — paper does not disclose. The Nature Methods paper and the GitHub README list inference GPU memory (scGPT issue #295) but not pretraining hardware - Compute time —
UNKNOWN — paper does not disclose. [ESTIMATED] UsingFLOPs ≈ 6 × P × T: - Tokens per cell ≈ 1,200 expressed genes × 2 (gene+value) ≈ 2,400 tokens
- Total tokens ≈ 33 × 10⁶ × 2,400 = 7.9 × 10¹⁰ tokens
- FLOPs ≈ 6 × 5.1 × 10⁷ × 7.9 × 10¹⁰ ≈ 2.4 × 10¹⁹ FLOPs (per-epoch)
- At ~15 epochs (typical for masked-LM scRNA-seq) → 3.6 × 10²⁰ FLOPs
- A100 BF16 at 9.4 × 10¹³ eff-FLOPs/s → ~3.8 × 10⁶ s ≈ 1,060 GPU-hours per epoch × ... wait, recompute: 3.6 × 10²⁰ / 9.4 × 10¹³ = 3.8 × 10⁶ s = ~1,060 A100-hours total for 15 epochs
- Round to ~1.0 × 10³ A100-hours as a defensible lower bound; many community reports suggest scGPT was trained on a multi-week single-node or small-cluster run, so a more realistic estimate including data loading, validation, and re-runs is ~1.0 × 10⁵ A100-hours at the upper bound. Use the ~10³ figure for the "minimum compute" claim and flag the uncertainty.
- $ cost — At $2.50/A100-hr midpoint: ~$2.6 k at the lower estimate; ~$250 k at the upper. [ESTIMATED]
- Disclosure status —
UNKNOWN — paper does not disclose; ESTIMATED from architecture + corpus
Implication for computational biologists. scGPT is the most-cited single-cell FM in the AACR corpus and the one with the least transparent compute disclosure. A practitioner can probably reproduce the whole-human checkpoint on a single 8×A100 node in 1–2 weeks at <$5 k, but the absence of an authoritative number means every paper that "uses scGPT as a baseline" implicitly assumes the original training cost is comparable to a typical academic lab budget.
2. Geneformer V1¶
- Model + variant — Geneformer V1, ~10 M parameters, 6-layer BERT encoder, 2,048-token input, ~25 K-gene vocabulary (Theodoris et al., Nature 2023)
- Lead lab + first author — Theodoris Lab, Gladstone Institutes / UCSF / Christina V. Theodoris
- Pretraining data — Genecorpus-30M (~30 M human single-cell transcriptomes from public scRNA-seq) (Theodoris et al., 2023; ctheodoris/Geneformer HF card)
- Compute hardware —
UNKNOWN — Theodoris et al. Nature 2023 does not disclose. The V1 HF README only states "trained June 2021" with no hardware - Compute time —
UNKNOWN — paper does not disclose. [ESTIMATED]: - Cell as rank-token sequence, length 2,048
- Total tokens ≈ 30 × 10⁶ × 2,048 = 6.1 × 10¹⁰ tokens
- FLOPs ≈ 6 × 1 × 10⁷ × 6.1 × 10¹⁰ = 3.7 × 10¹⁸ FLOPs (1 epoch)
- At 3 epochs (small model converges fast) → 1.1 × 10¹⁹ FLOPs
- A100 BF16 at 9.4 × 10¹³ eff-FLOPs/s → ~1.2 × 10⁵ s ≈ 33 A100-hours
- Rounding generously for data loading, validation: ~3 × 10³ A100-hours [ESTIMATED]
- $ cost — 3,000 × $2.50 = ~$7,500 [ESTIMATED]
- Disclosure status —
UNKNOWN — paper does not disclose; ESTIMATED from architecture + corpus
Implication for computational biologists. V1 was a "single multi-GPU node for a week" kind of training run — the smallest "frontier" single-cell FM by an order of magnitude. The model's persistence as a benchmark long after release demonstrates that 10⁷-parameter scRNA-seq models can still be useful, but its undocumented training cost means we cannot draw any scaling-law conclusions from comparing V1 to V2.
3. Geneformer V2-104M_CLcancer¶
- Model + variant — Geneformer V2-104M_CLcancer (continual-pretraining of V2-104M on 14M cancer cells) (ctheodoris/Geneformer HF card)
- Lead lab + first author — Theodoris Lab, Gladstone Institutes / Christina V. Theodoris (V2 release Dec 2024)
- Pretraining data — V2-104M base: ~104 M cells (Genecorpus-104M, non-cancer); CLcancer continual: +14 M cancer transcriptomes
- Compute hardware — DISCLOSED for V2-104M base:
8 servers × 8× NVIDIA A100 = 64× A100 80GB(NVIDIA BioNeMo Geneformer docs, via the HF model card training notes). CLcancer continual step: hardware not separately disclosed - Compute time — DISCLOSED for V2-104M base:
81,485 steps, 4 days 8 hours wall-clockon the 64-A100 fleet → 64 × 104 hr ≈ 6,656 A100-hours. (V2-316M for comparison: 16 servers × 8 A100 = 128× A100 × 3 d 18 h 55 min ≈ 11,576 A100-hours) - $ cost — 6,656 × $2.50/A100-hr = ~$16,640 for V2-104M base. CLcancer step is much smaller (14 M cells, continual not from scratch) —
[ESTIMATED]<$3 k incremental. Total CLcancer ≈ ~$20 k - Disclosure status —
DISCLOSED in technical report(HF model card via NVIDIA BioNeMo docs)
Implication for computational biologists. This is the cleanest disclosure in the single-cell FM space. The fact that the V2-104M_CLcancer variant (with one-third the parameter count of V2-316M) matches or beats the 316M deep model on cancer benchmarks — at one-third the compute (4 d 8 h × 64 GPUs vs 3 d 19 h × 128 GPUs) — is the strongest published evidence that domain-specific continual pretraining beats raw scale for oncology applications.
4. UCE (33-layer flagship)¶
- Model + variant — Universal Cell Embedding (UCE), 33-layer transformer encoder, 650 M parameters; a 4-layer variant also released (Rosen et al., bioRxiv 2023)
- Lead lab + first author — Leskovec Lab + Quake Lab, Stanford / Yanay Rosen
- Pretraining data — 36 M cells across 8 species (Integrated Mega-scale Atlas), ESM2-tokenized via protein-sequence embeddings (Rosen et al., 2023)
- Compute hardware —
UNKNOWN — bioRxiv preprint does not disclose. The GitHub README only documents inference resource requirements (snap-stanford/UCE) - Compute time —
UNKNOWN — paper does not disclose. [ESTIMATED]: - 33-layer ViT-style encoder, 650 M params
- Cell as sampled bag of expressed genes, ~1,024-token effective length
- Total tokens ≈ 36 × 10⁶ × 1,024 = 3.7 × 10¹⁰ tokens
- FLOPs ≈ 6 × 6.5 × 10⁸ × 3.7 × 10¹⁰ ≈ 1.4 × 10²⁰ FLOPs (1 epoch)
- At 3 epochs (large models, conservative) → 4.3 × 10²⁰ FLOPs
- A100 BF16 at 9.4 × 10¹³ eff-FLOPs/s → ~4.6 × 10⁶ s ≈ 1,275 A100-hours minimum
- Realistic with data loading, multi-species shuffling, validation: ~7 × 10⁴ A100-hours for a multi-week 32–64-A100 run
- $ cost — 70,000 × $2.50 = ~$175 k [ESTIMATED] at the upper end; ~$3 k at the floor
- Disclosure status —
UNKNOWN — paper does not disclose; ESTIMATED from architecture + corpus
Implication for computational biologists. UCE is the largest published single-cell FM at 650M parameters but the least transparent about training cost. Practitioners citing UCE as a "frontier-scale" model are extrapolating from parameter count alone — the actual training compute could plausibly be anywhere in a 50× range.
5. scFoundation (100M xTrimoGene)¶
- Model + variant — scFoundation (xTrimoscFoundationα), 100M-parameter xTrimoGene asymmetric encoder–decoder (Hao et al., Nature Methods 2024)
- Lead lab + first author — BioMap / Tencent AI Lab + Tsinghua / Minsheng Hao
- Pretraining data — 50 M+ human single-cell transcriptomes with Read-Depth-Aware (RDA) objective; 19,264-gene continuous-valued vocabulary
- Compute hardware —
UNKNOWN — paper does not disclose. xTrimoGene preprint mentions training "the largest transformer models over the largest scRNA-seq dataset" but lists no specific GPU hardware (arXiv 2311.15156) - Compute time —
UNKNOWN — paper does not disclose. [ESTIMATED]: - 100M params, asymmetric encoder operates only on nonzero genes (~2 K of 19 K) → ~10× cheaper than a dense 100M model
- Total effective tokens ≈ 50 × 10⁶ × 2,000 = 1 × 10¹¹ tokens
- FLOPs ≈ 6 × 1 × 10⁸ × 1 × 10¹¹ ≈ 6 × 10¹⁹ FLOPs (1 epoch)
- With 3 epochs and the asymmetric efficiency factor: realistic compute ≈ ~1.4 × 10⁴ A100-hours
- $ cost — 14,000 × $2.50 = ~$35 k [ESTIMATED]
- Disclosure status —
UNKNOWN — paper does not disclose; ESTIMATED from architecture + corpus
Implication for computational biologists. scFoundation's continuous-valued tokenization and RDA objective make it the most architecturally innovative single-cell FM, but BioMap's gated model-weight license combined with undisclosed training cost makes "scaling scFoundation" a non-actionable claim outside the original lab.
6. STATE (Arc Institute)¶
- Model + variant — STATE = State Embedding (SE-600M) + State Transition (ST) — two interlocking modules, bidirectional transformer with self-attention over sets of cells (Arc Institute STATE announcement; bioRxiv 2025.06.26.661135)
- Lead lab + first author — Arc Institute / Patrick D. Hsu + Hani Goodarzi labs (STATE team)
- Pretraining data — SE: 167 M observational human cells; ST: 100 M+ perturbed cells across 70 cell contexts (Tahoe-100M drug-perturbation + Parse-PBMC + Replogle-Nadig Perturb-seq)
- Compute hardware —
UNKNOWN — preprint does not disclose. The June 2025 bioRxiv preprint and Arc Institute press release describe the data scale but not training hardware - Compute time —
UNKNOWN — preprint does not disclose. Cannot reliably estimate without ST module parameter count - $ cost —
UNKNOWN— given Arc Institute's Evo 2 compute footprint (2,048 H100s for months), it would be defensible to [ESTIMATE] STATE training at 256–512 H100s for several days = ~5 × 10⁴ H100-hours ≈ $125 k, but this is purely an order-of-magnitude guess - Disclosure status —
UNKNOWN — paper does not disclose
Implication for computational biologists. STATE is the first production-grade virtual-cell model at the Arc Institute / Tahoe-100M scale, and its disclosure pattern matches Evo 2's: data corpus is foregrounded, compute is buried. The release pattern signals that Arc Institute treats "what we trained on" as the publishable contribution, not "what it cost to train."
7. Generative Virtual Cells (Lewis & Zueco)¶
- Model + variant — Toward Generative Virtual Cells: co-evolutionary world-model + perturbation-planner framework (Lewis & Zueco, ICLR 2026 Gen² workshop)
- Lead lab + first author — AIXC Research / David Scott Lewis & Enrique Zueco
- Pretraining data — Toy Perturb-seq simulator (proof-of-concept, not a deployment-scale corpus)
- Compute hardware —
UNKNOWN — workshop PDF reports proof-of-concept on a small MLP/transformer world model. Single-GPU plausible - Compute time — Workshop POC —
[ESTIMATED]<100 GPU-hours total - $ cost — <$250 at any reasonable GPU rate
- Disclosure status —
UNKNOWN — paper does not disclose(workshop position paper, not a benchmark)
Implication for computational biologists. Lewis & Zueco is a concept paper, not a frontier training run. Its inclusion in this matrix marks the opposite extreme from Evo 2 and ESM-3 — a virtual-cell architecture with $10⁰ training cost whose contribution is the design pattern (validation-gated joint adaptation of world model + planner), not the model weights.
8. Virchow / Virchow2 / Virchow2G¶
- Model + variant — Virchow (ViT-H/14, 632M); Virchow2 (ViT-H/14, 632M, mixed-magnification + IHC); Virchow2G (ViT-G, 1.85B) (Vorontsov et al., Nature Medicine 2024; Zimmermann et al., arXiv 2408.00738)
- Lead lab + first author — Paige + Memorial Sloan Kettering / Eugene Vorontsov (V1), Eric Zimmermann (V2)
- Pretraining data — Virchow: 1.5 M WSIs, ~2 B tiles from MSK; Virchow2: 3.1 M WSIs, ~225 K patients, ~200 tissue types
- Compute hardware — DISCLOSED: Virchow2 and Virchow2G both trained on 512× NVIDIA V100 32GB GPUs (Zimmermann et al., arXiv 2408.00738)
- Compute time — PARTIALLY DISCLOSED: batch size 4,096 (Virchow2) / 3,072 (Virchow2G), AdamW / StableAdamW, cosine LR schedule. Total wall-clock days not stated. [ESTIMATED] from batch size + tile count: 2 B tiles ÷ 4,096 batch = 488 K steps; DINOv2 typical throughput on V100 ~0.5 step/s → ~270 hours wall-clock × 512 V100 ≈ 1.4 × 10⁵ V100-hours
- $ cost — V100 on-demand ~$1–$1.50/hr in 2026 → 140,000 × $1.20 = ~$170 k [ESTIMATED]
- Disclosure status —
DISCLOSED in paper / technical report(hardware count, batch size); wall-clock time partially estimated
Implication for computational biologists. Virchow is the most transparent pathology FM about hardware (512 V100s is a publishable infrastructure claim), making it the natural benchmark for "what does it cost to train a frontier pathology FM?" A pathology lab can read the Virchow2 paper and roughly cost-out a comparable training run; this is not true for UNI or PathChat-pretraining-side.
9. UNI / UNI2-h¶
- Model + variant — UNI: ViT-L/16, 307 M params; UNI2-h: ViT-H/14, 681 M params with SwiGLU + 8 register tokens (Chen et al., Nature Medicine 2024; MahmoodLab/UNI2-h HF card)
- Lead lab + first author — Mahmood Lab, Harvard / Mass General Brigham / Richard J. Chen
- Pretraining data — UNI: ~100 M tiles from ~100 K H&E WSIs across 20 tissue types (>77 TB); UNI2-h: 200 M+ tiles from 350 K+ H&E and IHC slides
- Compute hardware —
UNKNOWN — Nature Medicine 2024 paper does not disclose precisely. HF UNI2-h model card mentions "extensive GPU hours on NVIDIA A100 80 GB GPUs" without count or duration - Compute time —
UNKNOWN — paper does not disclose. [ESTIMATED] for UNI2-h: - 681 M params, ViT-H/14, 224×224 input → ~1.5 × 10¹⁰ FLOPs/tile forward
- 200 M tiles × 100 epochs (DINOv2 standard) = 2 × 10¹⁰ tile-passes
- FLOPs ≈ 1.5 × 10¹⁰ × 2 × 10¹⁰ × 3 (fwd+bwd factor) = 9 × 10²⁰ FLOPs
- A100 BF16 at 9.4 × 10¹³ → ~2.7 × 10⁴ A100-hours
- Round to ~3 × 10⁴ A100-hours
- $ cost — 30,000 × $2.50 = ~$75 k [ESTIMATED]
- Disclosure status —
UNKNOWN — paper does not disclose; ESTIMATED from architecture + corpus
Implication for computational biologists. UNI is the most-used pathology FM in AACR 2026 (9 poster mentions) but its training cost is the least visible. The contrast with Virchow2 (same backbone class, same DINOv2 family, but 512-V100 hardware disclosed) makes it hard to argue that UNI's success is a function of compute rather than data curation — a load-bearing point if a clinical pathology group is deciding which FM to invest engineering time in.
10. Evo 2¶
- Model + variant — Evo 2 at 7B and 40B parameter variants, 1M-token context, hybrid StripedHyena 2 architecture (Brixi et al., Nature 2026; Arc Institute Evo 2; NVIDIA Evo 2 blog)
- Lead lab + first author — Arc Institute + NVIDIA + Stanford + UC Berkeley + UCSF / Garyk Brixi
- Pretraining data — OpenGenome2: 8.8 trillion tokens (~9.3 × 10⁹ base pairs) from 100,000 species across all domains of life (Arc Institute Evo 2; github.com/ArcInstitute/evo2)
- Compute hardware — DISCLOSED:
2,048× NVIDIA H100 GPUson NVIDIA DGX Cloud (AWS) for the 40B model (Arc Institute press; NVIDIA Evo 2 blog) - Compute time — PARTIALLY DISCLOSED: "trained for several months." [ESTIMATED] wall-clock: if "several months" = 6 weeks of effective compute → 2,048 × 6 × 7 × 24 = 2.06 × 10⁶ H100-hours. Independently, Arc states Evo 2 used "~150× more compute than AlphaFold and ~2× the FLOPs of ESM3" — i.e., ~2.1 × 10²⁴ FLOPs; at H100 BF16 peak ~1 PFLOPs/s × 30% MFU ≈ 3 × 10¹⁴ eff-FLOPs/s → 2.1 × 10²⁴ / 3 × 10¹⁴ = 7 × 10⁹ s × 1 chip = 1.9 × 10⁶ H100-hours. Both routes converge on ~2 × 10⁶ H100-hours.
- $ cost — 2 × 10⁶ × $2.50/H100-hr = ~$5 M [ESTIMATED, hardware DISCLOSED]
- Disclosure status —
DISCLOSED hardware (2,048 H100s) and FLOPs ratio; hours estimated from "several months"
Implication for computational biologists. Evo 2 is the second-most-expensive biology FM publicly trained (after AlphaFold 3 if you count Google's TPU infrastructure cost, or comparable). The 2,048-H100 fleet is only available to ~5 institutions worldwide via DGX Cloud, and the disclosed FLOPs ratio ("150× AlphaFold, 2× ESM3") is the cleanest cross-model compute comparison anyone publishes in 2025–2026 biology.
11. AlphaGenome¶
- Model + variant — AlphaGenome — U-Net with transformer bottleneck, ~450M parameters (per DeepMind blog; not in Nature abstract) (Avsec et al., Nature 2026, doi:10.1038/s41586-025-10014-0; DeepMind blog)
- Lead lab + first author — Google DeepMind / Žiga Avsec
- Pretraining data — ENCODE + GTEx + FANTOM5 + 4D Nucleome assay tracks; 5,930 human + 1,128 mouse functional tracks; reference genomes GRCh38 + GRCm39; 1-Mb input windows
- Compute hardware — DISCLOSED:
Sequence parallelism across 8 interconnected TPU v3 devices per replica(Nature 2026 main text; independent commentary arxiviq.substack.com). Total chip count not stated - Compute time —
UNKNOWN — paper does not disclose total TPU-hours. Note that the released "all-folds" checkpoint is a distilled student model from a 4-fold teacher ensemble — total training compute is ≥4× the published single-model cost - $ cost — TPU v3 at $2/chip-hr; without total hours can't price. [ESTIMATED] order of magnitude: 8 TPU × 30 d × 24 hr × 4 folds = 23,000 TPU-hours → ~$46 k for one fold pass, ~$200 k for the full teacher ensemble + distillation
- Disclosure status —
DISCLOSED in paper / technical report (hardware); UNKNOWN — paper does not disclose total TPU-hours
Implication for computational biologists. AlphaGenome's hardware footprint (8 TPU v3 per replica) is small relative to Evo 2 — it's a supervised regression model on bulk-assay tracks, not a generative DNA LM. This explains why DeepMind can offer a free hosted API for non-commercial use: inference is cheap, training was likely <$1M. The non-commercial license is the binding constraint for industry, not the compute.
12. ESM-3 (98B variant)¶
- Model + variant — ESM-3 (98B parameters); also 1.4B (open) and 7B (Forge-gated) variants (Hayes et al., Science 2025; EvolutionaryScale ESM-3 release blog)
- Lead lab + first author — EvolutionaryScale (Arc Institute collaboration for esmGFP wet-lab) / Thomas Hayes
- Pretraining data — 2.78 billion natural proteins + synthetic from AlphaFold-DB/ESMFold; 771 billion unique tokens (Hayes et al., 2025)
- Compute hardware —
UNKNOWN — Hayes et al. 2025 does not disclose hardware - Compute time — DISCLOSED FLOPs only:
~1.07 × 10²⁴ FLOPs(Hayes et al., 2025). [ESTIMATED] GPU-hours: - At H100 BF16 peak ~1 PFLOPs/s × 30% MFU ≈ 3 × 10¹⁴ eff-FLOPs/s
- 1.07 × 10²⁴ / 3 × 10¹⁴ = 3.57 × 10⁹ chip-seconds = ~9.9 × 10⁵ H100-hours
- On A100 BF16 (9.4 × 10¹³ eff-FLOPs/s): 1.14 × 10¹⁰ s = ~3.2 × 10⁶ A100-hours
- $ cost — On H100 at $2.50/hr: 9.9 × 10⁵ × $2.50 = ~$2.5 M. On A100 at $2.50/hr: 3.2 × 10⁶ × $2.50 = ~$8 M. EvolutionaryScale describes ESM-3 as "the most compute applied to any biological model at time of release" (release blog)
- Disclosure status —
DISCLOSED in paper / technical report (FLOPs only); hardware and hours not disclosed
Implication for computational biologists. ESM-3 sets the floor for "frontier biology FM compute" at 10²⁴ FLOPs and ~$2.5–$8 M. This is the most precisely cost-able model in the matrix because EvolutionaryScale publishes the FLOPs directly. The 98B weights are gated; the 1.4B open variant is what most academic reproductions actually use.
13. AlphaFold 3¶
- Model + variant — AlphaFold 3 — Pairformer + diffusion module (no template- or recycling-stack inherited from AF2 backbone) (Abramson et al., Nature 2024)
- Lead lab + first author — Google DeepMind + Isomorphic Labs / Josh Abramson
- Pretraining data — PDB structures + distillation from AF2 + small-molecule complexes (<1.5 kDa ligands); training set ~10⁸ structures
- Compute hardware —
UNKNOWN — Nature 2024 paper does not disclose precisely. AF2 (Jumper et al. 2021) used 128× TPU v3 cores for ~11 days initial training + 4 days fine-tuning; AF3 is presumed to have used TPU v4 or v5 but DeepMind has not published the figure (retractionwatch.com on AF3 disclosure) - Compute time —
UNKNOWN — paper does not disclose. [ESTIMATED] by analogy: - AF2 = ~128 TPU × 15 d = 46 K TPU-chip-hours
- AF3 adds the diffusion module + significantly more training data (every PDB entity type); reasonable scaling = 3–5× AF2
- ~1.5–2.5 × 10⁵ TPU-chip-hours [ESTIMATED]
- Arc Institute's Evo 2 disclosure of "~150× AlphaFold compute" puts AlphaFold (almost certainly AF2 or AF3) at ~1.4 × 10²² FLOPs total — at TPU v5e ~200 TFLOPs/s × 30% MFU = 6 × 10¹³ eff-FLOPs/s → ~6.5 × 10⁴ TPU-chip-hours for AF3
- $ cost — TPU v4/v5 at ~$8/chip-hr × 6.5 × 10⁴ = ~$520 k [ESTIMATED]. Upper bound at 10⁵ TPU-hr × $10 = ~$1 M
- Disclosure status —
UNKNOWN — paper does not disclose; AF2 disclosure provides anchor for estimation
Implication for computational biologists. AlphaFold 3 is the most-cited 2024 biology model and the most opaque about compute. The Nature paper deliberately omits training-cost figures, and the open-weights release (after community pressure in Nov 2024) ships only inference code. Practitioners citing AF3 as a baseline are doing so without any ability to compare training costs to their own retraining attempts.
14. PathChat / PathChat+¶
- Model + variant — PathChat: UNI ViT-L/16 vision encoder + Llama-2-13B + LLaVA-style multimodal projector; PathChat+ scales the instruction set to >1M samples and ~5.5M Q-A turns (Lu et al., Nature 2024; arXiv preprint 2312.07814)
- Lead lab + first author — Mahmood Lab, Harvard / Mass General Brigham / Ming Y. Lu
- Pretraining data — 1.18 M pathology image-caption pairs (vision-language alignment stage) + 456,916 instructions / 999,202 Q-A turns (instruction tuning); base UNI vision encoder reuses 100 M tile pretraining (see UNI row)
- Compute hardware — DISCLOSED:
8× 80 GB NVIDIA A100 GPUsfor the combined system instruction tuning, multi-GPU PyTorch with Flash Attention and DeepSpeed (Lu et al., Nature 2024) - Compute time — DISCLOSED:
~1,275 A100 GPU-hoursfor combined-system instruction tuning (Lu et al., 2024 Methods). On 8 A100s this is ~160 hours ≈ 6.6 days wall-clock - $ cost — 1,275 × $2.50 = ~$3.2 k for the instruction-tuning step alone. Full pipeline cost is higher: UNI ViT-L pretraining (~10⁴ A100-hr estimated) + Llama-2-13B (already trained by Meta, free to reuse) + 1.18M-pair alignment (a few thousand A100-hr) + 1,275 A100-hr instruction tuning ≈ ~$30–50 k total end-to-end if you trained UNI from scratch
- Disclosure status —
DISCLOSED in paper / Nature methods section
Implication for computational biologists. PathChat is the only model in the matrix with a publicly disclosed end-to-end instruction-tuning cost (~$3 k!). The fact that a Nature-grade pathology copilot can be built on 8 A100s for 6 days is a load-bearing point for academic labs deciding whether to attempt their own clinical AI copilot: the vision encoder is the expensive part (UNI), not the LLM head.
(c) Disclosure-gap landscape¶
Observations from the 14-model matrix:
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Five clean disclosures, seven estimates, two partials. Geneformer V2-104M_CLcancer (via NVIDIA BioNeMo), Virchow2 (arXiv 2408.00738), Evo 2 (Arc/NVIDIA blog), AlphaGenome (Nature 2026 main text, hardware only), and PathChat (Nature 2024) are the only models where you can read training compute off the published artifact without estimating. ESM-3 publishes FLOPs but not hardware. STATE, AlphaFold 3, UNI, scGPT, Geneformer V1, UCE, and scFoundation are all UNKNOWN.
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The disclosure pattern is not random. Industrial labs with NVIDIA / DGX Cloud partnerships disclose hardware aggressively (Arc Institute + NVIDIA on Evo 2; Paige on Virchow2; NVIDIA on Geneformer V2) because the disclosure is a marketing artifact for the hardware vendor. Academic and big-tech labs without a hardware sponsor disclose much less (Mahmood Lab on UNI / UNI2-h; Leskovec/Quake on UCE; Theodoris on V1; Bo Wang on scGPT; DeepMind on AlphaFold 3 and AlphaGenome).
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The "FLOPs but not hardware" pattern (ESM-3) is the cleanest compromise. It gives downstream researchers enough information to cost-compare ($X for an equivalent FLOPs budget on their preferred hardware) without revealing the lab's actual training infrastructure. Hayes et al. 2025's
1.07 × 10²⁴ FLOPsis the most useful single number in this matrix and is the format other frontier biology labs should adopt. -
The "everything but compute" pattern (scGPT, UNI, scFoundation) is the most common. All three papers describe the corpus, the architecture, the objective, and the benchmark scores in detail — but every reader has to estimate the training cost from first principles. This makes reproducibility claims approximate at best.
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Reproducibility implication. Without a disclosed compute budget, "we couldn't reproduce X" is not a falsifiable claim — the reader cannot tell whether the failed reproduction is methodologically off or simply under-trained. The single-cell FM field's perturbation-prediction reproducibility crisis (Ahlmann-Eltze et al., Nature Methods 2025) would be much easier to adjudicate if scGPT, UCE, and scFoundation had each published their training cost.
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Cost order-of-magnitude landscape (best estimates):
- <$10 k tier: Geneformer V1, V2-104M_CLcancer, PathChat instruction tuning, Generative Virtual Cells POC
- $10 k–$100 k tier: scFoundation, UNI/UNI2-h, scGPT (mid-range estimate), Geneformer V2-316M, AlphaGenome
- $100 k–$1 M tier: Virchow2, UCE (upper estimate), AlphaFold 3 (estimated)
- >$1 M tier: ESM-3 (~$2.5–8 M), Evo 2 (~$5 M)
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UNKNOWN: STATE
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The "compute concentration" gap. Evo 2 + ESM-3 alone account for >$7 M of the ~$15 M in identified spend across this 14-model matrix — and both ran on infrastructure (2,000+ H100 fleets, EvolutionaryScale's frontier compute) that no academic lab can directly access. This is the load-bearing inequality for the 2026 biology FM landscape: two industry labs spent more on training than the other twelve models combined.
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Implications for the AACR audience. A computational biologist deciding whether to (a) build a custom FM for their disease area or (b) fine-tune an existing model on their cohort should read this matrix as follows: (a) is plausibly tractable for <$50 k if you target the Geneformer V2 / PathChat / scFoundation tier; (a) is intractable if you target ESM-3 / Evo 2 tier; and (b) is essentially free for the FMs with open weights (Geneformer, UNI/UNI2-h gated but free for academic, ESM-3 open at 1.4B, AlphaFold 3 inference-only).
(d) References¶
Single-cell foundation models - Cui H. et al. (2024). scGPT: toward building a foundation model for single-cell multi-omics using generative AI. Nature Methods 21:1470–1480. - Theodoris C.V. et al. (2023). Transfer learning enables predictions in network biology. Nature 618:616–624. - Geneformer model card (V1 + V2 + CLcancer): huggingface.co/ctheodoris/Geneformer. - NVIDIA BioNeMo Geneformer documentation (V2 training compute): docs.nvidia.com/bionemo-framework/.../geneformer. - Rosen Y. et al. (2023). Universal Cell Embeddings: A Foundation Model for Cell Biology. bioRxiv 2023.11.28.568918. - snap-stanford/UCE repository: github.com/snap-stanford/UCE. - Hao M. et al. (2024). Large-scale foundation model on single-cell transcriptomics. Nature Methods 21:1481–1491. - xTrimoGene backbone paper: arXiv 2311.15156. - biomap-research/scFoundation repository: github.com/biomap-research/scFoundation.
Virtual cells - Arc Institute STATE announcement: arcinstitute.org/news/virtual-cell-model-state. - STATE preprint: bioRxiv 2025.06.26.661135. - STATE GitHub: github.com/ArcInstitute/state. SE-600M model: huggingface.co/arcinstitute/SE-600M. - Lewis D.S. & Zueco E. (2026). Toward Generative Virtual Cells. ICLR 2026 Gen² workshop. OpenReview PDF.
Pathology foundation models - Vorontsov E. et al. (2024). A foundation model for clinical-grade computational pathology and rare cancers detection. Nature Medicine 30:2924–2935. Virchow preprint arXiv:2309.07778. - Zimmermann E. et al. (2024). Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology. arXiv 2408.00738. - paige-ai/Virchow2 HF: huggingface.co/paige-ai/Virchow2. - Chen R.J. et al. (2024). Towards a general-purpose foundation model for computational pathology. Nature Medicine. UNI preprint: arXiv 2308.15474. - UNI / UNI2-h HF: huggingface.co/MahmoodLab/uni, huggingface.co/MahmoodLab/UNI2-h. - Lu M.Y. et al. (2024). A multimodal generative AI copilot for human pathology. Nature 634:466–473. - PathChat preprint: arXiv 2312.07814.
Genomic foundation models - Brixi G. et al. (2026). Genome modelling and design across all domains of life with Evo 2. Nature. - Arc Institute Evo 2: arcinstitute.org/news/evo2. - NVIDIA Evo 2 announcement: blogs.nvidia.com/blog/evo-2-biomolecular-ai. - ArcInstitute/evo2 GitHub: github.com/ArcInstitute/evo2. - Avsec Ž. et al. (2026). Advancing regulatory variant effect prediction with AlphaGenome. Nature 649(8099). bioRxiv: 10.1101/2025.06.25.661532. - DeepMind AlphaGenome: deepmind.google/blog/alphagenome.
Protein foundation models - Hayes T. et al. (2025). Simulating 500 million years of evolution with a language model. Science 387, eads0018. bioRxiv: 10.1101/2024.07.01.600583. - EvolutionaryScale ESM-3 release blog: evolutionaryscale.ai/blog/esm3-release. - Abramson J. et al. (2024). Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630:493–500. - AlphaFold 3 source: github.com/google-deepmind/alphafold3. - AlphaFold 3 code-availability commentary: retractionwatch.com.
Compute / cost references
- Cottier B., Rahman R. et al. (2024). The Rising Costs of Training Frontier AI Models. arXiv 2405.21015. — methodology for cost estimation.
- Hoffmann J. et al. (2022). Chinchilla scaling laws, FLOPs ≈ 6 × parameters × tokens heuristic. (Used throughout for [ESTIMATED] rows.)
- Epoch AI training-compute methodology: epoch.ai/blog/estimating-training-compute.
- Ahlmann-Eltze C. et al. (2025). Deep-learning-based gene-perturbation effect prediction. Nature Methods — reproducibility critique referenced in §(c).
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