Dataset Information

Multiplexed Quantitative Proteomics Provides Mechanistic Cues for Malaria Severity and Complexity

ABSTRACT: Management of severe malaria remains a critical global challenge. In this study, using a multiplexed quantitative proteomics pipeline we systematically investigated the plasma proteome alterations in non-severe and severe malaria patients. We identified a few parasite proteins in severe malaria patients, which could be promising from a diagnostic perspective. Further, from host proteome analysis we observed substantial modulations in many crucial physiological pathways, including lipid metabolism, cytokine signaling, complement, and coagulation cascades in severe malaria. We propose that severe manifestations of malaria are possibly underpinned by modulations of the host physiology and defense machinery, which is evidently reflected in the plasma proteome alterations. Importantly, we identified multiple blood markers that can effectively define different complications of severe falciparum malaria, including cerebral syndromes and severe anemia. The ability of our identified blood markers to distinguish different severe complications of malaria may aid in developing new clinical tests for monitoring malaria severity.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Vipin Kumar

LAB HEAD: Sanjeeva Srivastava

PROVIDER: PXD014991 | Pride | 2020-11-06

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	01032018_Fusion_Vipin_R7F1.raw	Raw
	01032018_Fusion_Vipin_R7F2.raw	Raw
	01032018_Fusion_Vipin_R7F3.raw	Raw
	01032018_Fusion_Vipin_R7F4.raw	Raw
	01032018_Fusion_Vipin_R7F5.raw	Raw

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Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity.

Kumar Vipin V Ray Sandipan S Aggarwal Shalini S Biswas Deeptarup D Jadhav Manali M Yadav Radha R Sabnis Sanjeev V SV Banerjee Soumaditya S Talukdar Arunansu A Kochar Sanjay K SK Shetty Suvin S Sehgal Kunal K Patankar Swati S Srivastava Sanjeeva S

Communications biology 20201117 1

Management of severe malaria remains a critical global challenge. In this study, using a multiplexed quantitative proteomics pipeline we systematically investigated the plasma proteome alterations in non-severe and severe malaria patients. We identified a few parasite proteins in severe malaria patients, which could be promising from a diagnostic perspective. Further, from host proteome analysis we observed substantial modulations in many crucial physiological pathways, including lipid metabolis ...[more]

PMID: 33204009

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Project description:Mechanisms regulating gene expression in malaria parasites are not well understood. Little is known about how this parasite regulates its gene expression during transition from one developmental stage to another and in response to various environmental conditions. Parasites in a diseased host face environments which differ from the static, well adapted in vitro conditions in culture. Parasites thus need to adapt quickly and effectively to these conditions by establishing transcriptional states which is best suited for better survival. With the discovery of natural antisense transcripts (NATs) in this parasite and considering the various proposed mechanisms by which NATs might regulate gene expression, it has been speculated that these might be playing a critical role in gene regulation. We report here the diversity of NATs that exist in this parasite, using isolates taken directly from patients with differing clinical symptoms caused by malaria infection. A total of 797 NATs targeted against annotated loci have been detected using a custom designed strand specific microarray. Out of these, 545 are unique to this study. The majority of NATs were positively correlated with the expression pattern of the sense transcript. Many were found to be differentially regulated in response to disease conditions. Antisense transcripts mapped to a wide variety of biochemical/ metabolic pathways, especially pathways pertaining to the central carbon metabolism and stress related pathways. Our data strongly suggests that a large group of NATs detected here are unannotated transcription units antisense to annotated gene models. The results reveal a previously unknown set of NATs that prevails in this parasite, their differential regulation in disease conditions and mapping to functionally well annotated genes. The results detailed here call for studies to deduce the possible mechanism of action, which would help in understanding the in vivo pathological adaptations of these parasites. Plasmodium falciparum isolates were collected from patients (n = 11) with differing clinical conditions.The patients exhibited symptoms categorized as un-complicated (n =2) or complicated malaria (n = 9). Criteria for determination of complicated disease were based on World Health Organization year 2000 guidelines. Microarray array based transcriptional profiling was carried out to detect prevalence of natural antisense transcript.