RegFM

RegFM is a context-aware foundation model for human transcriptional regulation.
It treats regulation as a dialogue between cis-regulatory sequences (CREs) and trans-acting regulators (transcription factors and chromatin regulators), coupling long-range CRE representations with TF/CR activity.

Trained on large-scale ENCODE and CELLxGENE transcriptomic profiles, RegFM learns gene-centered regulatory representations that generalize across unseen cellular contexts.

GitHub

RegFM overview

Model description

  • Inputs: long-range cis-DNA sequence features + cell-context TF/CR and expression signals
  • Outputs: gene expression predictions and regulatory representations usable for downstream tasks
  • Framework: PyTorch

Intended uses

  • Gene expression prediction in unseen cellular contexts
  • Cis-regulatory element annotation
  • Bivalent promoter / dosage-sensitivity related analyses
  • Perturbation-response prediction
  • Interpretable analysis of cis–trans regulatory interactions

Code & demo

Code, training/prediction scripts, and a PBMC leave-one-out demo (predict on held-out CD8 TEM 1) live on GitHub:

https://github.com/ZjGaothu/RegFM

pip install git+https://github.com/ZjGaothu/RegFM.git
# or clone and: pip install -e .

Citation

If you use RegFM, please cite:

Zijing Gao, et al. RegFM: an interpretable context-aware foundation model for human transcriptional regulation. bioRxiv, (2026).
(DOI will be added upon public release.)

Contact

gzj21@mails.tsinghua.edu.cn

License

MIT

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