EnergoRNA

Complementary classifier for Variants of Uncertain Significance (VUS)
via mRNA thermodynamic fingerprinting

Language: English · Español

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This project has evolved into EnergyFingerprint, which includes the full open-source implementation, reproducible notebooks, and validated results across 8 genes and 4 protein families.

EnergyFingerprint

The method originally described under the EnergoRNA name has been substantially expanded and published as EnergyFingerprint: a lightweight 1D-CNN (~228K parameters) that classifies missense variants as pathogenic or benign by combining mRNA thermodynamic stacking profiles with ESM-1v protein language model scores.

Key results (8 genes validated):

Gene	Disease	Intra-gene AUC	Zero-shot AUC
BRCA1	Breast/ovarian cancer	0.943	--- (train)
TP53	Multi-cancer	0.907	0.854
PTEN	Multi-cancer	0.994	0.975
PALB2	Breast cancer	0.950	0.954
CFTR	Cystic fibrosis	0.979	0.777
HBB	Sickle cell disease	0.721	0.707
SCN1A	Epilepsy/Dravet	0.868	0.637
MECP2	Rett syndrome	0.911	0.430

For the full code, notebooks, and documentation, visit: github.com/josevilar-qbioai/energyfingerprint

Patent

This technology is the subject of a Spanish patent application:

• Title: Método y sistema para el análisis termodinámico de transcritos de mRNA mediante perfiles de energía de apilamiento a resolución de nucleótido y redes neuronales convolucionales unidimensionales
• Application number: P202630522
• Filing date: April 11, 2026
• Applicant: Jose Antonio Vilar Sanchez
• Office: Oficina Española de Patentes y Marcas (OEPM)
• Status: Pending examination

Citation

If you reference this work in academic publications, please cite:

@article{vilar2026energyfingerprint,
  title={EnergyFingerprint: mRNA Thermodynamic Profiling Combined with Protein
         Language Models Enables Zero-Shot Cross-Gene Missense Variant Classification},
  author={Vilar Sanchez, Jose Antonio},
  year={2026},
  doi={10.5281/zenodo.19831154}
}

Contact

• Author: Jose Antonio Vilar Sanchez
• Email: qmetrika@proton.me
• ORCID: 0009-0008-1057-4223

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EnergoRNA — Decoding variants through the energy of RNA