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Empathi: embedding-based phage protein annotation tool by hierarchical assignment.

Alexandre Boulay1,2, Audrey Leprince3, François Enault4

  • 1Département de biochimie, de microbiologie et de bio-informatique, Université Laval, Québec, QC, Canada. alexandreboulay@outlook.com.

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|October 14, 2025
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Summary
This summary is machine-generated.

Bacteriophages (viruses that infect bacteria) have many unknown protein functions. A new tool, Empathi, uses protein embeddings to classify these functions, significantly improving annotation accuracy and understanding phage roles in ecosystems.

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Area of Science:

  • Microbiology
  • Bioinformatics
  • Virology

Background:

  • Bacteriophages are abundant viruses crucial to microbial ecosystems.
  • Rapid evolution of bacteriophages results in many proteins with unknown functions.
  • Existing methods for phage protein function identification lack sensitivity or specificity.

Purpose of the Study:

  • To introduce Empathi, a novel protein-embedding-based classifier for hierarchical phage protein function assignment.
  • To develop new, hierarchically organized functional categories for phage proteins suitable for machine learning.

Main Methods:

  • Empathi utilizes protein embeddings for function classification.
  • Hierarchical functional categories were specifically designed for phage proteins.
  • Performance was evaluated on cultured phage genomes and the EnVhogDB database.

Main Results:

  • Empathi significantly outperforms homology-based methods in annotating phage protein functions.
  • It tripled the number of annotated homologous groups on cultured phage genomes.
  • Empathi doubled the annotated fraction of protein families in the EnVhogDB database (from 16% to 33%).

Conclusions:

  • Empathi provides a more sensitive and specific method for identifying phage protein functions.
  • Improved functional annotation enhances understanding of phage biology and their interactions with bacteria.
  • This tool aids in deciphering the functional repertoire of phages in various ecosystems.