tSFM — Transcription Factor ↔ DNA Binding-Site 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 transcription factor (TF) protein sequences and DNA binding-site sequences via contrastive (InfoNCE) learning. Given a TF, retrieve the most likely DNA binding motif — or score TF–DNA pairs directly via cosine similarity.
| Component | Model |
|---|---|
| Agent encoder | ESM-2 (protein language model) |
| Target encoder | DNABERT-2 |
| Training data | JASPAR 2022 (1,060 TFs, 15,425 DNA motifs; 20,540 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 (%) |
|---|---|---|---|
| TF → DNA | 83.1 ± 3.0 | 98.9 ± 0.4 | 99.6 ± 0.5 |
| DNA → TF | 25.8 ± 2.5 | 45.0 ± 2.3 | 53.8 ± 2.6 |
*Paper fold-0 pool-512 R@1 (TF→DNA) = 81.5%.*
Quick start
from huggingface_hub import hf_hub_download
import torch, torch.nn.functional as F
ckpt_path = hf_hub_download("SFM-BIIE-ETHZ/tSFM_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("MTEYKLVVVGAGGVGKSALTIQLIQNHFV...") # TF protein
target_emb = model.encode_target("GCACGTGC") # DNA motif
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
@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