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EuPathDomains: the divergent domain database for eukaryotic pathogens.

Amel Ghouila1, Nicolas Terrapon, Olivier Gascuel

  • 1Méthodes et Algorithmes pour la Bioinformatique, LIRMM, CNRS, Univ. Montpellier 2, 161 rue Ada, Montpellier Cedex 5, France. amel.ghouila@lirmm.fr

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
|October 6, 2010
PubMed
Summary

EuPathDomains enhances protein function annotation in eukaryotic pathogens by identifying missed protein domains. This new database improves the discovery of therapeutic targets in organisms like Plasmodium and Leishmania.

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Area of Science:

  • Genomics and Bioinformatics
  • Parasitology
  • Drug Discovery

Background:

  • Eukaryotic pathogens cause significant global morbidity and mortality, particularly in Africa.
  • Despite available genome sequences, the functions of many pathogen proteins remain unknown, hindering therapeutic target identification.
  • Protein domain identification is crucial for functional annotation, but traditional methods miss domains in evolutionarily distant pathogens.

Purpose of the Study:

  • To present EuPathDomains, an extended database of protein domains for ten major eukaryotic human pathogens.
  • To improve the functional annotation of proteins in these pathogens by identifying novel and missed domains.
  • To provide a valuable resource for discovering new therapeutic targets.

Main Methods:

  • Utilized the co-occurrence domain detection (CODD) method to enhance Pfam domain detection sensitivity.
  • Developed EuPathDomains, a database integrating known and CODD-detected domains with confidence scores and Gene Ontology (GO) annotations.
  • The database allows querying by protein names, domain identifiers (Pfam, Interpro), and organisms.

Main Results:

  • EuPathDomains significantly extends Pfam domain coverage in selected pathogen genomes.
  • It identifies new domain occurrences and novel domain families previously unreported.
  • For instance, it increased detected domains by up to 28% in Cryptosporidium parvum and domain families by 16% in Plasmodium falciparum (at <20% FDR).

Conclusions:

  • EuPathDomains substantially improves protein domain discovery in eukaryotic pathogens.
  • The database offers a valuable resource for deciphering protein functions and identifying potential therapeutic targets.
  • This work addresses a critical gap in understanding pathogen biology and facilitates drug development efforts.