A top-down approach to infer and compare domain-domain interactions across eight model organisms

Chittibabu Guda, Brian R. King, Lipika R. Pal, Purnima Guda

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Knowledge of specific domain-domain interactions (DDIs) is essential to understand the functional significance of protein interaction networks. Despite the availability of an enormous amount of data on protein-protein interactions (PPIs), very little is known about specific DDIs occurring in them. Here, we present a top-down approach to accurately infer functionally relevant DDIs from PPI data. We created a comprehensive, non-redundant dataset of 209,165 experimentally-derived PPIs by combining datasets from five major interaction databases. We introduced an integrated scoring system that uses a novel combination of a set of five orthogonal scoring features covering the probabilistic, evolutionary, evidence-based, spatial and functional properties of interacting domains, which can map the interacting propensity of two domains in many dimensions. This method outperforms similar existing methods both in the accuracy of prediction and in the coverage of domain interaction space. We predicted a set of 52,492 high-confidence DDIs to carry out cross-species comparison of DDI conservation in eight model species including human, mouse, Drosophila, C. elegans, yeast, Plasmodium, E. coli and Arabidopsis. Our results show that only 23% of these DDIs are conserved in at least two species and only 3.8% in at least 4 species, indicating a rather low conservation across species. Pair-wise analysis of DDI conservation revealed a 'sliding conservation' pattern between the evolutionarily neighboring species. Our methodology and the high-confidence DDI predictions generated in this study can help to better understand the functional significance of PPIs at the modular level, thus can significantly impact further experimental investigations in systems biology research.

Original languageEnglish (US)
Article numbere5096
JournalPloS one
Volume4
Issue number3
DOIs
StatePublished - Mar 31 2009

Fingerprint

protein-protein interactions
organisms
Conservation
Proteins
prediction
Plasmodium
Protein Interaction Domains and Motifs
functional properties
Protein Interaction Maps
Drosophila
Systems Biology
methodology
Arabidopsis
yeasts
Escherichia coli
Biological Sciences
mice
Yeast
Yeasts
Databases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

A top-down approach to infer and compare domain-domain interactions across eight model organisms. / Guda, Chittibabu; King, Brian R.; Pal, Lipika R.; Guda, Purnima.

In: PloS one, Vol. 4, No. 3, e5096, 31.03.2009.

Research output: Contribution to journalArticle

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