Abstract
BackgroundCerebral malaria is a form of human malaria wherein Plasmodium falciparum-infected red blood cells adhere to the blood capillaries in the brain, potentially leading to coma and death. Interactions between parasite and host proteins are important in understanding the pathogenesis of this deadly form of malaria. It is, therefore, necessary to study available protein-protein interactions to identify lesser known interactions that could throw light on key events of cerebral malaria.MethodsSequestration, haemostasis dysfunction, systemic inflammation and neuronal damage are key processes of cerebral malaria. Key events were identified from literature as being crucial to these processes. An integrated interactome was created using available experimental and predicted datasets as well as from literature. Interactions from this interactome were filtered based on Gene Ontology and tissue-specific annotations, and further analysed for relevance to the key events.ResultsPfEMP1 presentation, platelet activation and astrocyte dysfunction were identified as the key events influencing the disease. 48896 host-parasite along with other host-parasite, host-host and parasite-parasite protein-protein interactions obtained from a disease-specific corpus were combined to form an integrated interactome. Filtering of the interactome resulted in five host-parasite PPI, six parasite-parasite and two host-host PPI. The analysis of these interactions revealed the potential significance of apolipoproteins and temperature/Hsp expression on efficient PfEMP1 presentation; role of MSP-1 in platelet activation; effect of parasite proteins in TGF-β regulation and the role of albumin in astrocyte dysfunction.ConclusionsThis work links key host-parasite, parasite-parasite and host-host protein-protein interactions to key processes of cerebral malaria and generates hypotheses for disease pathogenesis based on a filtered interaction dataset. These hypotheses provide novel and significant insights to cerebral malaria.
Highlights
Cerebral malaria is a form of human malaria wherein Plasmodium falciparum-infected red blood cells adhere to the blood capillaries in the brain, potentially leading to coma and death
Host- P. falciparum protein interactionsProtein-protein interactions (PPI) were obtained by unifying all the datasets
Host-P. falciparum, host-host and parasite-parasite PPI reported in literature were obtained by analysing this Cerebral malaria (CM)-specific literature corpus. 48,896 host-parasite PPI from the various PPI datasets along with the host-parasite, host-host and parasite-parasite PPI obtained from the literature analysis were combined to form an integrated interactome
Summary
Cerebral malaria is a form of human malaria wherein Plasmodium falciparum-infected red blood cells adhere to the blood capillaries in the brain, potentially leading to coma and death. Interactions between parasite and host proteins are important in understanding the pathogenesis of this deadly form of malaria. It is, necessary to study available protein-protein interactions to identify lesser known interactions that could throw light on key events of cerebral malaria. Cerebral malaria (CM) is a severe form of P. falciparum infection, characterized by cerebral complications, such as neuronal damage and coma [3] Processes such as sequestration, systemic inflammation, haemostasis dysfunction and neuronal damage characterize CM [4,5]. The landscape includes upstream PPI involving only parasite proteins as well as downstream PPI involving only host proteins that are necessary to understand the triggers and outcomes of these processes and events, respectively
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