Learning Shared Residue Backgrounds and Modification-Specific Offsets for PTM Site Prediction

Suresh Pokharel, Bishnu Bhusal

bioRxiv, 2026

Preprint

Abstract

Post-translational modifications (PTMs) are chemical changes added to proteins after translation. These changes affect protein function and regulation, and their disruption is linked to disease-associated mechanisms. Because experimentally validating all possible modification sites is impractical, many computational predictors have been developed for PTM site prediction. In this work, we study whether a shared model can represent common residue-background patterns while learning modification-specific background-to-positive offsets. We propose an anchor-guided rectified flow matching framework for multi-type PTM site prediction from protein language model embeddings. For each PTM-residue pair, the model builds residue-background anchors from PTM-compatible unannotated residues and positive anchors from experimentally annotated modified residues, and uses a rectified flow module to estimate a modification-conditioned background-to-positive offset. We evaluate the framework on a dbPTM-derived benchmark covering six commonly studied PTMs.

Cite this work

Download BibTeX · Download RIS · This record describes a preprint.

    @article{pokharel2026ptm,
  title = {Learning Shared Residue Backgrounds and Modification-Specific Offsets for PTM Site Prediction},
  author = {Pokharel, Suresh and Bhusal, Bishnu},
  journal = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.05.743079},
  url = {https://doi.org/10.64898/2026.08.05.743079}
}

    

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