Ortholog-based protein-protein interaction prediction and its application to inter-species interactions.
BACKGROUND
The rapid growth of protein-protein interaction (PPI) data has led to the emergence of PPI network analysis. Despite advances in high-throughput techniques, the interactomes of several model organisms are still far from complete. Therefore, it is desirable to expand these interactomes with ortholog-based and other methods.


RESULTS
Orthologous pairs of 18 eukaryotic species were expanded and merged with experimental PPI datasets. The contributions of interologs from each species were evaluated. The expanded orthologous pairs enable the inference of interologs for various species. For example, more than 32,000 human interactions can be predicted. The same dataset has also been applied to the prediction of host-pathogen interactions. PPIs between P. falciparum calmodulin and several H. sapiens proteins are predicted, and these interactions may contribute to the maintenance of host cell Ca2+ concentration. Using comparisons with Bayesian and structure-based approaches, interactions between putative HSP40 homologs of P. falciparum and the H. sapiens TNF receptor associated factor family are revealed, suggesting a role for these interactions in the interference of the human immune response to P. falciparum.


CONCLUSIONS
The PPI datasets are available from POINT http://point.bioinformatics.tw/ and POINeT http://poinet.bioinformatics.tw/. Further development of methods to predict host-pathogen interactions should incorporate multiple approaches in order to improve sensitivity, and should facilitate the identification of targets for drug discovery and design.
Lee
Sheng-An
SA
Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan. d93922005@ntu.edu.tw
Chan
Cheng-hsiung
CH
Tsai
Chi-Hung
CH
Lai
Jin-Mei
JM
Wang
Feng-Sheng
FS
Kao
Cheng-Yan
CY
Huang
Chi-Ying F
CY
D000818:Animals; D001499:Bayes Theorem; D002118:Calcium / Q000737:chemistry; D002147:Calmodulin / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D054884:Host-Pathogen Interactions; D006801:Humans; D007107:Immune System; D008954:Models, Biological; D008957:Models, Genetic; D010963:Plasmodium falciparum / Q000378:metabolism*; D025941:Protein Interaction Mapping; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013045:Species Specificity
D002147:Calmodulin; D018124:Receptors, Tumor Necrosis Factor; D002118:Calcium