Abstract
The study of molecular host–parasite interactions is essential to understand parasitic infection and adaptation within the host system. As well, prevention and treatment of infectious diseases require a clear understanding of the molecular crosstalk between parasites and their hosts. Yet, large-scale experimental identification of host–parasite molecular interactions remains challenging, and the use of computational predictions becomes then necessary. Here, we propose a computational integrative approach to predict host—parasite protein—protein interaction (PPI) networks resulting from the human infection by 15 different eukaryotic parasites. We used an orthology-based approach to transfer high-confidence intraspecies interactions obtained from the STRING database to the corresponding interspecies homolog protein pairs in the host–parasite system. Our approach uses either the parasites predicted secretome and membrane proteins, or only the secretome, depending on whether they are uni- or multi-cellular, respectively, to reduce the number of false predictions. Moreover, the host proteome is filtered for proteins expressed in selected cellular localizations and tissues supporting the parasite growth. We evaluated the inferred interactions by analyzing the enriched biological processes and pathways in the predicted networks and their association with known parasitic invasion and evasion mechanisms. The resulting PPI networks were compared across parasites to identify common mechanisms that may define a global pathogenic hallmark. We also provided a study case focusing on a closer examination of the human–S. mansoni predicted interactome, detecting central proteins that have relevant roles in the human–S. mansoni network, and identifying tissue-specific interactions with key roles in the life cycle of the parasite. The predicted PPI networks can be visualized and downloaded at http://orthohpi.jensenlab.org.
Highlights
Parasites are responsible for many diseases that result in millions of deaths each year
Our predictions returned a total of 27,352 interactions for 14,340 proteins (12,218 host proteins, 2,122 parasite proteins) being T. gondii and C. hominis the largest and the smallest predicted protein—protein interaction (PPI) networks, respectively (Table 2)
Regarding visceral leishmaniasis (L. donovani, L. infantum) we found 40 specific GO terms associated with a relevant biological process in the host–parasite interaction such as regulation of defense response to virus by virus and receptor-mediated endocytosis
Summary
Parasites are responsible for many diseases that result in millions of deaths each year. The World Health Organization published data in 2016 estimating that Plasmodium falciparum alone was responsible for around 214 million malaria cases, and 438,000 deaths worldwide [1]. Around 7 million people worldwide were reported to be infected with Trypanosoma cruzi, which causes Chagas disease that results in life-long morbidity and disability and more than 7,000 deaths per year [1]. Another highly prevalent disease, Leishmaniasis accounts for 20 to 30 thousand deaths a year and is caused by protozoan parasites of the Leishmania genus [1]. There is an urgent need to develop novel drugs or vaccines
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