{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:05:49Z","timestamp":1792037149987,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009870","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000}}],"reference-count":88,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32LM012416"],"award-info":[{"award-number":["T32LM012416"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI119881"],"award-info":[{"award-number":["R21AI119881"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI119881"],"award-info":[{"award-number":["R21AI119881"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37AI026649"],"award-info":[{"award-number":["R37AI026649"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI026649"],"award-info":[{"award-number":["R01AI026649"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001797","name":"Pharmaceutical Research and Manufacturers of America Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001797","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1211869"],"award-info":[{"award-number":["OPP1211869"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Virginia\u2019s Engineering-in-Medicine program"},{"name":"University of Virginia\u2019s Engineering-in-Medicine program"},{"name":"University of Virginia\u2019s Engineering-in-Medicine program"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Protozoan parasites cause diverse diseases with large global impacts. Research on the pathogenesis and biology of these organisms is limited by economic and experimental constraints. Accordingly, studies of one parasite are frequently extrapolated to infer knowledge about another parasite, across and within genera. Model\n                    <jats:italic>in vitro<\/jats:italic>\n                    or\n                    <jats:italic>in vivo<\/jats:italic>\n                    systems are frequently used to enhance experimental manipulability, but these systems generally use species related to, yet distinct from, the clinically relevant causal pathogen. Characterization of functional differences among parasite species is confined to\n                    <jats:italic>post hoc<\/jats:italic>\n                    or single target studies, limiting the utility of this extrapolation approach. To address this challenge and to accelerate parasitology research broadly, we present a functional comparative analysis of 192 genomes, representing every high-quality, publicly-available protozoan parasite genome including\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    ,\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    ,\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    ,\n                    <jats:italic>Entamoeba<\/jats:italic>\n                    ,\n                    <jats:italic>Trypanosoma<\/jats:italic>\n                    ,\n                    <jats:italic>Leishmania<\/jats:italic>\n                    ,\n                    <jats:italic>Giardia<\/jats:italic>\n                    , and other species. We generated an automated metabolic network reconstruction pipeline optimized for eukaryotic organisms. These metabolic network reconstructions serve as biochemical knowledgebases for each parasite, enabling qualitative and quantitative comparisons of metabolic behavior across parasites. We identified putative differences in gene essentiality and pathway utilization to facilitate the comparison of experimental findings and discovered that phylogeny is not the sole predictor of metabolic similarity. This knowledgebase represents the largest collection of genome-scale metabolic models for both pathogens and eukaryotes; with this resource, we can predict species-specific functions, contextualize experimental results, and optimize selection of experimental systems for fastidious species.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1009870","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T13:40:55Z","timestamp":1645623655000},"page":"e1009870","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Comparative analyses of parasites with a comprehensive database of genome-scale metabolic models"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-5445","authenticated-orcid":true,"given":"Maureen A.","family":"Carey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1571-0801","authenticated-orcid":true,"given":"Gregory L.","family":"Medlock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-9061","authenticated-orcid":true,"given":"Micha\u0142","family":"Stolarczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7268-1218","authenticated-orcid":true,"given":"William A.","family":"Petri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6301-4563","authenticated-orcid":true,"given":"Jennifer L.","family":"Guler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2769-5805","authenticated-orcid":true,"given":"Jason A.","family":"Papin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"pcbi.1009870.ref001","volume-title":"World Malaria Report 2018","author":"World Health Organization","year":"2019"},{"key":"pcbi.1009870.ref002","first-page":"1","article-title":"Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis","volume":"v\u2013xii","author":"World Health Organization","year":"2012","journal-title":"World Health Organ Tech Rep Ser"},{"key":"pcbi.1009870.ref003","article-title":"Weekly epidemiological record Relev\u00e9 \u00e9pid\u00e9miologique hebdomadaire","volume":"20","author":"World Health Organization","year":"2018","journal-title":"Weekly Epidemiological Report"},{"key":"pcbi.1009870.ref004","volume-title":"Essentials of Veterinary Parasitology.","author":"HM Elsheikha","year":"2011"},{"key":"pcbi.1009870.ref005","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/1756-3305-4-49","article-title":"One health: the importance of companion animal vector-borne diseases","volume":"4","author":"MJ Day","year":"2011","journal-title":"Parasit Vectors"},{"key":"pcbi.1009870.ref006","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.tree.2007.08.009","article-title":"Parasites, people and policy: infectious diseases and the Millennium Development Goals","volume":"22","author":"RM May","year":"2007","journal-title":"Trends Ecol Evol"},{"key":"pcbi.1009870.ref007","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1016\/S0140-6736(09)60571-7","article-title":"The Bill & Melinda Gates Foundation\u2019s grant-making programme for global health","volume":"373","author":"D McCoy","year":"2009","journal-title":"Lancet"},{"key":"pcbi.1009870.ref008","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2147\/DDDT.S146521","article-title":"Leishmaniasis in humans: drug or vaccine therapy?","volume":"12","author":"M Ghorbani","year":"2018","journal-title":"Drug Des Devel Ther"},{"key":"pcbi.1009870.ref009","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/ni.2853","article-title":"Vaccines against tropical parasitic diseases: a persisting answer to a persisting problem","volume":"15","author":"DL Sacks","year":"2014","journal-title":"Nat Immunol"},{"key":"pcbi.1009870.ref010","doi-asserted-by":"crossref","first-page":"e0006985","DOI":"10.1371\/journal.pntd.0006985","article-title":"A therapeutic preconceptional vaccine against Chagas disease: A novel indication that could reduce congenital transmission and accelerate vaccine development","volume":"13","author":"E Dumonteil","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"pcbi.1009870.ref011","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41579-018-0148-3","article-title":"How elusive can a malaria vaccine be?","volume":"17","author":"A. 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