Host–pathogen protein interactions predicted by comparative modeling
- 1 December 2007
- journal article
- research article
- Published by Wiley in Protein Science
- Vol. 16 (12), 2585-2596
- https://doi.org/10.1110/ps.073228407
Abstract
Pathogens have evolved numerous strategies to infect their hosts, while hosts have evolved immune responses and other defenses to these foreign challenges. The vast majority of host-pathogen interactions involve protein-protein recognition, yet our current understanding of these interactions is limited. Here, we present and apply a computational whole-genome protocol that generates testable predictions of host-pathogen protein interactions. The protocol first scans the host and pathogen genomes for proteins with similarity to known protein complexes, then assesses these putative interactions, using structure if available, and, finally, filters the remaining interactions using biological context, such as the stage-specific expression of pathogen proteins and tissue expression of host proteins. The technique was applied to 10 pathogens, including species of Mycobacterium, apicomplexa, and kinetoplastida, responsible for ''neglected'' human diseases. The method was assessed by (1) comparison to a set of known host-pathogen interactions, (2) comparison to gene expression and essentiality data describing host and pathogen genes involved in infection, and (3) analysis of the functional properties of the human proteins predicted to interact with pathogen proteins, demonstrating an enrichment for functionally relevant host-pathogen interactions. We present several specific predictions that warrant experimental follow-up, including interactions from previously characterized mechanisms, such as cytoadhesion and protease inhibition, as well as suspected interactions in hypothesized networks, such as apoptotic pathways. Our computational method provides a means to mine whole-genome data and is complementary to experimental efforts in elucidating networks of host-pathogen protein interactions.Keywords
This publication has 71 references indexed in Scilit:
- Ensembl 2007Nucleic Acids Research, 2006
- IntAct--open source resource for molecular interaction dataNucleic Acids Research, 2006
- Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial proteaseProceedings of the National Academy of Sciences of the United States of America, 2006
- Protein complex compositions predicted by structural similarityNucleic Acids Research, 2006
- A gene atlas of the mouse and human protein-encoding transcriptomesProceedings of the National Academy of Sciences of the United States of America, 2004
- BIND: the Biomolecular Interaction Network DatabaseNucleic Acids Research, 2003
- Statistical potentials for fold assessmentProtein Science, 2002
- Gene Expression Omnibus: NCBI gene expression and hybridization array data repositoryNucleic Acids Research, 2002
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997
- Comparative Protein Modelling by Satisfaction of Spatial RestraintsJournal of Molecular Biology, 1993