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Updated: Jan 12, 2026

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A deep learning framework for lysine 2-hydroxyisobutyrylation site prediction using evolutionary feature

Heba M Elreify1, Fathi E Abd El-Samie2,3, Moawad I Dessouky2

  • 1Department of Electronics and Electrical Communication Engineering, Faculty of Electronic Engineering, Menoufia University, Menouf, 32952, Egypt. hebamohamedibrahim09@gmail.com.

Scientific Reports
|November 6, 2025
PubMed
Summary
This summary is machine-generated.

A new deep-learning tool, BLOS-Khib, accurately predicts Lysine 2-hydroxyisobutyrylation (Khib) sites across species. This computational approach enhances understanding of this crucial post-translational modification in diverse organisms.

Keywords:
Blosum62Cross-speciesDeep learningLysine 2-hydroxyisobutyrylationPost-translational modifications

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Area of Science:

  • Biochemistry and Molecular Biology
  • Computational Biology
  • Genomics

Background:

  • Lysine 2-hydroxyisobutyrylation (Khib) is a vital post-translational modification (PTM) involved in gene expression and metabolic regulation.
  • Accurate computational prediction of Khib sites is currently limited, hindering research in this area.

Purpose of the Study:

  • To develop and validate a novel deep-learning framework, BLOS-Khib, for accurate cross-species prediction of Khib sites.
  • To identify conserved and species-specific sequence features associated with Khib modification.

Main Methods:

  • A deep-learning framework (Convolutional Neural Network - CNN) was developed, incorporating evolutionary information from the BLOSUM62 matrix.
  • Systematic optimization determined the optimal peptide length (43 amino acids) for sequence context.
  • Performance was evaluated across six diverse organisms, including human, wheat, rice, T. gondii, Candida albicans, and Botrytis cinerea.

Main Results:

  • BLOS-Khib achieved high predictive performance, with Area Under the ROC Curve (AUC) values ranging from 0.885 to 0.913 on independent test sets.
  • The framework outperformed existing state-of-the-art methods, including traditional machine learning and other deep learning architectures.
  • Sequence signature analysis revealed conserved lysine-rich regions and species-specific flanking amino acid preferences.
  • High transferability of the model across evolutionarily distant organisms was observed.

Conclusions:

  • BLOS-Khib offers a robust and accurate computational tool for predicting Khib sites across diverse species.
  • The study provides evolutionary insights into the sequence determinants of Khib modification, suggesting convergent evolution.
  • BLOS-Khib advances the field of PTM prediction and understanding of Khib's regulatory roles.