Posted by Kasra
In silico prediction of protein-protein interactions within a species is an advancing field. Especially now that relatively large amounts of empirical data are available for training and validation, more and more in silico methods are being presented. However, as a host-parasite interactions enthusiast, I always had the question if the interactions between the host and pathogen proteins can be predicted. Although already done a few times for viruses such as HSV, HCV, HIV and Influenza, creation of an empirical inter-species interactome is not an easy and always affordable task. Still having an interactome database provides very valuable data in host-pathogen research. It not only reveals systemic overviews about the nature of the interaction occuring, but it can also open doors for more accessible and feasible research by suggesting a shorter list of proteins, pathways or interactions to focus on.
With this in mind, I had great pleasure in reading this single author paper by Stefan Wuchty published recently in PloS ONE that provides a computational interactome of Plasmodium falciparum and Homo sapiens. This paper actually led me to a whole body of research that has been done on experimental and computational determination of host-pathogen interactomes, albeit mostly on viruses.
In order to map P. falciparum – H. sapiens interactome, Wuchty used experimentally determined host-parasite interactions plus orthologous protein groups between the two species as starting point. The false-positives were removed with various filtering methods that are beyond the reach of my knowledge of mathematics and informatics. Biological criteria such as co-expression of the interacting proteins in the host cell and specific parasite phase were also required. Interstingly, the pattern of interactions he found, showed similarity with what was already observed with viral pathogens. In order to take control of the cell, intracellular pathogens appear to attack the host both at the protein as well as the pathway level. Hub proteins – proteins that interact with many other proteins and are envolved in multiple metabolic/siganling pathways – have been found to be an attack target not only by P. falciparum but also other pathogens. In addition, Wutchy saw that a relatively small number of human proteins interact with a big number of parasite proteins, suggesting that the parasite utilizes all it has got to take over the key proteins of the host.
This study and other works of the same style certainly provide precious knowledge about host-parasite interactions both in terms of systems biology and also hints for hands on research. I look forward to seeing these interactomes created and expanded for other pathogens and also their experimental validation and usage. Furthermore, an online database of these host-parasite interactomes would definitely make them more accessible.
Wuchty S (2011). Computational Prediction of Host-Parasite Protein Interactions between P. falciparum and H. sapiens. PloS one, 6 (11) PMID: 22114664