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Its unique biology makes it resilient to control measures that are otherwise effective against<jats:italic>P. falciparum<\/jats:italic>. A deeper understanding of<jats:italic>P. vivax<\/jats:italic>biology and pathogenesis is, therefore, essential for developing the right control strategies. Proteomics of<jats:italic>P. falciparum<\/jats:italic>has been helpful in studying disease biology and elucidating molecular mechanisms involved in the development of disease. However, unlike<jats:italic>P. falciparum<\/jats:italic>, proteomics data for<jats:italic>P. vivax<\/jats:italic>infection is minimal due to the absence of a continuous culture system. The dependence on clinical samples and animal models has drastically limited<jats:italic>P. vivax<\/jats:italic>research, creating critical knowledge gaps in our understanding of the disease. This study describes an in-depth proteomics analysis of<jats:italic>P. vivax<\/jats:italic>-infected human plasma and parasite isolates, to understand parasite biology, pathogenesis, and to identify new diagnostic targets for<jats:italic>P. vivax<\/jats:italic>malaria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A mass-spectrometry- (MS) based proteomics approach (Q Exactive) was applied to analyze human plasma and parasite isolates from vivax malaria patients visiting a primary health centre in India. Additionally, a targeted proteomics assay was standardized for validating unique peptides of most recurring parasite proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty-eight<jats:italic>P. vivax<\/jats:italic>proteins were detected in human plasma with high confidence. Several glycolytic enzymes were found along with hypothetical, cytoskeletal, ribosomal, and nuclear proteins. Additionally, 103 highly abundant<jats:italic>P. vivax<\/jats:italic>proteins were detected in parasite isolates. This represents the highest number of parasite proteins to be reported from clinical samples so far. Interestingly, five of these; three<jats:italic>Plasmodium<\/jats:italic>exported proteins (PVX_003545, PVX_003555 and PVX_121935), a hypothetical protein (PVX_083555) and Pvstp1 (subtelomeric transmembrane protein 1, PVX_094303) were found in both plasma and parasite isolates<jats:italic>.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A parasite proteomics investigation is essential to understand disease pathobiology and design novel interventions. Control strategies against<jats:italic>P. vivax<\/jats:italic>also depend on early diagnosis. This work provides deeper insights into the biology of<jats:italic>P. vivax<\/jats:italic>by identifying proteins expressed by the parasite during its complex life-cycle within the human host. The study also reports antigens that may be explored as diagnostic candidates.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12879-020-4885-3","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T19:02:51Z","timestamp":1583175771000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Comprehensive proteomics investigation of P. vivax-infected human plasma and parasite isolates"],"prefix":"10.1186","volume":"20","author":[{"given":"Apoorva","family":"Venkatesh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Aggarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srushti","family":"Rajyaguru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipin","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheetal","family":"Bankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanthi","family":"Shastri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Patankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5159-6834","authenticated-orcid":false,"given":"Sanjeeva","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,2]]},"reference":[{"key":"4885_CR1","volume-title":"World Malaria Report","author":"World Health Organization (WHO)","year":"2017","unstructured":"World Health Organization (WHO), World Malaria Report, 2017."},{"key":"4885_CR2","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1186\/1475-2875-13-481","volume":"13","author":"BA Rahimi","year":"2014","unstructured":"Rahimi BA, Thakkinstian A, White NJ, Sirivichayakul C, Dondorp AM, Chokejindachai W. 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