mimicDetector: a pipeline for protein motif mimicry detection in host-pathogen interactions

Kaylee D Rich1, James D Wasmuth1

  • 1Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, T2N 4Z6, Canada.

PubMed
Abstract

Insights

Pathogens use molecular mimicry to evade immune responses. A new bioinformatics tool, mimicDetector, effectively identifies these mimicry instances between pathogens and hosts, revealing potential therapeutic targets.

Area of Science:

  • Bioinformatics
  • Immunology
  • Pathogen-Host Interactions

Background:

  • Molecular mimicry is a strategy employed by pathogens to evade host immune defenses and manipulate cellular processes.
  • Detection of molecular mimicry is challenging due to short sequence motifs in non-homologous proteins, requiring sensitive and specific bioinformatics tools.

Purpose of the Study:

  • To develop and present mimicDetector, a novel k-mer-based pipeline for identifying protein-level molecular mimicry.
  • To assess the capability of mimicDetector in identifying biologically plausible mimicry candidates between pathogens and hosts.

Main Methods:

  • Developed a k-mer-based bioinformatics pipeline named mimicDetector.
  • Implemented the pipeline using Python and Snakemake for compatibility with Unix-based systems.
  • Applied mimicDetector to analyze molecular mimicry in 17 globally important pathogens.

Main Results:

  • mimicDetector successfully identified a wide range of potential molecular mimicry candidates between pathogens and their hosts.
  • Identified helminth proteins mimicking components of the human complement system.
  • Discovered a Leishmania infantum mimic of Reticulon-4, a key regulator of immune cell recruitment.

Conclusions:

  • mimicDetector is a sensitive and specific tool for identifying molecular mimicry.
  • The identified mimicry candidates provide insights into pathogen evasion strategies and potential targets for therapeutic intervention.
  • The tool is publicly available, facilitating further research in pathogen-host interactions.