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Prokaryotic genomes exhibit a streamlined organization of coding and non-coding regions essential for gene expression and protein synthesis. While coding regions contain the genetic instructions for proteins or functional RNAs, non-coding regions regulate the precise transcription and translation of these genes.Coding Regions: Proteins and RNAsThe primary coding regions, known as structural genes, include sequences transcribed into messenger RNA (mRNA) and ultimately translated into...
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A Protocol for Computer-Based Protein Structure and Function Prediction
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SAP: Synteny-aware gene function prediction for bacteria using protein embeddings.

Aysun Urhan1,2, Bianca-Maria Cosma1, Ashlee M Earl2

  • 1Delft Bioinformatics Lab, Delft University of Technology Van Mourik, Broekmanweg 6, 2628 XE, Delft, The Netherlands.

Biorxiv : the Preprint Server for Biology
|May 19, 2023
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Summary

Predicting bacterial gene function is challenging. A new tool, SAP, uses protein language models and bacterial operon structure to accurately predict gene functions, even for novel proteins, and identified potential new toxins.

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Area of Science:

  • Genomics
  • Bioinformatics
  • Microbial genomics

Background:

  • The function of most bacterial proteins remains unknown, hindering our understanding of microbial biology and potential applications.
  • Existing gene function prediction methods often fail for bacteria due to a lack of homologous sequences in databases and a focus on eukaryotic models.

Approach:

  • Developed SAP, a novel synteny-aware gene function prediction tool utilizing protein embeddings from advanced protein language models.
  • Integrated bacterial operon structure and conserved synteny into the prediction model to enhance accuracy for prokaryotes.

Key Points:

  • SAP significantly outperforms conventional sequence-based and current state-of-the-art methods in bacterial gene function prediction.
  • The tool demonstrates high efficacy in detecting distant homologs, even with sequence similarity as low as 40% to known proteins.
  • SAP successfully identified 11 previously unrecognized putative novel toxins in diverse enterococci species.

Conclusions:

  • SAP offers an improved approach for bacterial gene function prediction, addressing limitations of existing methods.
  • The tool has identified potential novel toxins in clinically relevant enterococci, highlighting its significance for human and animal health research.