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In malaria parasites, GPI-anchored proteins (GPI-APs) have been shown to play an important role in host\u2013pathogen interactions and a key function in host cell invasion and immune evasion. Because of their immunogenic properties, some of these proteins have been considered as malaria vaccine candidates. However, identification of all possible GPI-APs encoded by these parasites remains challenging due to their sequence diversity and limitations of the tools used for their characterization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The FT-GPI software was developed to detect GPI-APs based on the presence of a hydrophobic helix at both ends of the premature peptide. FT-GPI was implemented in C\u2009++and applied to study the GPI-proteome of 46 isolates of the order Haemosporida. Using the GPI proteome of<jats:italic>Plasmodium falciparum<\/jats:italic>strain 3D7 and<jats:italic>Plasmodium vivax<\/jats:italic>strain Sal-1, a heuristic method was defined to select the most sensitive and specific FT-GPI software parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>FT-GPI enabled revision of the GPI-proteome of<jats:italic>P. falciparum<\/jats:italic>and<jats:italic>P. vivax,<\/jats:italic>including the identification of novel GPI-APs. Orthology- and synteny-based analyses showed that 19 of the 37 GPI-APs found in the order Haemosporida are conserved among<jats:italic>Plasmodium<\/jats:italic>species. Our analyses suggest that gene duplication and deletion events may have contributed significantly to the evolution of the GPI proteome, and its composition correlates with speciation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>FT-GPI-based prediction is a useful tool for mining GPI-APs and gaining further insights into their evolution and sequence diversity. This resource may also help identify new protein candidates for the development of vaccines for malaria and other parasitic diseases.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12936-022-04430-0","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T16:02:55Z","timestamp":1674662575000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["FT-GPI, a highly sensitive and accurate predictor of GPI-anchored proteins, reveals the composition and evolution of the GPI proteome in Plasmodium species"],"prefix":"10.1186","volume":"22","author":[{"given":"Lena M.","family":"Sauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Canovas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Roche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hosam","family":"Shams-Eldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Ravel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Colinge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph T.","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choukri","family":"Ben Mamoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Rivals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Cornillot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"4430_CR1","volume-title":"World malaria report 2021","author":"WHO","year":"2022","unstructured":"WHO. 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