Abstract
To obtain candidates of interactions between proteins of the malaria parasite Plasmodium falciparum and the human host, homologous and conserved interactions were inferred from various sources of interaction data. Such candidate interactions were assessed by applying a machine learning approach and further filtered according to expression and molecular characteristics, enabling involved proteins to indeed interact. The analysis of predicted interactions indicated that parasite proteins predominantly target central proteins to take control of a human host cell. Furthermore, parasite proteins utilized their protein repertoire in a combinatorial manner, providing a broad connection to host cellular processes. In particular, several prominent pathways of signaling and regulation proteins were predicted to interact with parasite chaperones. Such a result suggests an important role of remodeling proteins in the interaction interface between the human host and the parasite. Identification of such molecular strategies that allow the parasite to take control of the host has the potential to deepen our understanding of the parasite specific remodeling processes of the host cell and illuminate new avenues of disease intervention.
Highlights
Little is known about large-scale protein interactions between cells, large-scale maps are an important foundation for the understanding of the ways pathogens interact, invade and seize control of their human hosts
Sequence homology is a powerful technique, large inserts obscure homology signals in gene/protein sequences of P. falciparum that might hamper the detection of orthologs in different organisms
To ensure utmost biological relevance, predicted interactions were further filtered that involved parasite proteins with parasite specific characteristics, making the underlying parasite protein conducive to interact with the human host
Summary
Little is known about large-scale protein interactions between cells, large-scale maps are an important foundation for the understanding of the ways pathogens interact, invade and seize control of their human hosts. Uetz et al released the first small map of computationally inferred physical protein interactions between the human host, the Kaposi-Sarcoma associated Herpesvirus and the Varicella-Zoster-Virus [1]. In another approach, Calderwood et al [2] experimentally constructed a map of physical protein interactions between the Epstein-Barr-Virus and the human host. Dyer et al compared experimentally known interactions of different viruses with the human host [9]
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