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Detection of new protein domains using co-occurrence: application to Plasmodium falciparum

Nicolas Terrapon1, Olivier Gascuel, Eric Maréchal

  • 1Méthodes et algorithmes pour la Bioinformatique, LIRMM, Université Montpellier 2, CNRS, 161 rue Ada, 34392 Montpellier Cedex 5, France.

Bioinformatics (Oxford, England)
|September 30, 2009
PubMed
Abstract

Insights

This study introduces a new method to enhance protein domain detection in Plasmodium falciparum, identifying hundreds of novel Pfam domains and improving Gene Ontology annotations for malaria research.

Area of Science:

  • Genomics
  • Bioinformatics
  • Computational Biology

Background:

  • Hidden Markov Models (HMMs) are effective for protein domain identification.
  • Highly divergent proteins, such as those in Plasmodium falciparum, often lead to missed domain detections.
  • Plasmodium falciparum is the primary cause of human malaria.

Purpose of the Study:

  • To improve the sensitivity of HMM-based protein domain detection.
  • To identify novel protein domains in Plasmodium falciparum.
  • To enhance functional annotation of the Plasmodium proteome.

Main Methods:

  • Developed a novel method leveraging the co-occurrence patterns of protein domains.
  • Utilized existing Pfam and InterPro domain information to infer presence of missed domains.
  • Employed a shuffling procedure to estimate the false discovery rate.

Main Results:

  • Identified 585 new Pfam domains in Plasmodium falciparum, adding to the 3683 known domains.
  • Achieved an estimated false discovery rate below 20% for the newly identified domains.
  • Generated 387 new Gene Ontology (GO) annotations for the P. falciparum proteome.
  • Obtained similar results for related Plasmodium species (P. vivax, P. yoelii).

Conclusions:

  • The proposed method significantly enhances protein domain detection sensitivity for divergent proteins.
  • The newly identified domains and GO annotations provide valuable insights into Plasmodium biology.
  • This approach aids in understanding malaria parasite genetics and developing new interventions.

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