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SFM-BIIE-ETHZ/crisprSFM_VC-SFM

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crisprSFM — CRISPR gRNA ↔ Off-Target DNA Specificity Foundation Model

Paper: Vibe Coding Specificity Foundation Models · doi: 10.64898/2026.06.04.730134 All VC-SFM models: huggingface.co/SFM-BIIE-ETHZ Code: github.com/SFM-BIIE-ETHZ/Vibe-Coding-SFMs

What it does

This SFM learns a joint embedding space for CRISPR guide RNAs (gRNAs) and candidate off-target genomic DNA sites via contrastive learning. Given a gRNA, retrieve the most likely off-target loci for rapid off-target risk assessment.

Component	Model
Agent encoder	DNABERT-2
Target encoder	DNABERT-2
Training data	CCLMoff (1,668 guides / 30,308 off-target sites; 30,342 pairs)
Split	Sequence-identity 100% holdout · fold 0

Performance — pool-512 retrieval (from the paper)

Evaluated by pool-512 retrieval: each test pair's true target is placed in a pool of 512 candidates (1 positive + 511 random negatives), scored by cosine similarity, over 100 random trials at the best-validation checkpoint. Random baseline = 0.2%. Values are the 5-fold cross-validated mean ± SD (folds 0–3; fold 4 excluded for split degeneracy) reported in the paper for this SFM. The released checkpoint is the fold-0, identity-100 model trained with the identical configuration, data, and split.

Direction	R@1 (%)	R@5 (%)	R@10 (%)
gRNA → off-target	95.4 ± 6.5	98.6 ± 2.1	99.0 ± 1.5
off-target → gRNA	74.8 ± 20.2	82.2 ± 18.2	86.0 ± 14.9

Paper fold-0 pool-512 R@1 (gRNA→off-target) = 98.6%.

Quick start

python

from huggingface_hub import hf_hub_download
import torch, torch.nn.functional as F

ckpt_path = hf_hub_download("SFM-BIIE-ETHZ/crisprSFM_VC-SFM", "model.pth")

# Load with the Vibe-Coding-SFMs codebase
# (https://github.com/SFM-BIIE-ETHZ/Vibe-Coding-SFMs)
from calm.encoder.model import CALMEncoder
model = CALMEncoder.from_pretrained(ckpt_path)
model.eval()

agent_emb  = model.encode_query("GAGTCCGAGCAGAAGAAGAA")        # 20-nt gRNA (no PAM)
target_emb = model.encode_target("GAGTCCGAGCAGAAGAAGAANGG")    # 23-nt off-target + PAM

score = F.cosine_similarity(agent_emb, target_emb, dim=-1)

Files in this repo

File	Description
`model.pth`	Released checkpoint · fold 0 · identity-100 split
`results_train_val_test.csv`	Per-epoch training/validation/test logs (training-time batch metrics, not the pool-512 numbers above)

Citation

bibtex

@article{reddy2026vcsfm,
  title   = {Vibe Coding Specificity Foundation Models},
  author  = {Reddy, Sai T.},
  journal = {bioRxiv},
  year    = {2026},
  doi     = {10.64898/2026.06.04.730134}
}

License

Released under the SFM Research Preview License v1.0-preview (see LICENSE.md). Free for research use — academic, non-profit, government, and industry research. The specific molecules disclosed in the accompanying preprints are dedicated to the public. Commercial-use and patent-licensing terms are deferred and being arranged with ETH Zürich / BIIE; the SFM architectures and training methods are the subject of pending patent applications. For commercial enquiries: sai.reddy@ethz.ch