{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T04:59:57Z","timestamp":1774155597364,"version":"3.50.1"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["104111\/Z\/14\/ZR"],"award-info":[{"award-number":["104111\/Z\/14\/ZR"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Parasites use polymorphic gene families to evade the immune system or interact with the host. Assessing the diversity and expression of such gene families in pathogens can inform on the repertoire or host interaction phenotypes of clinical relevance. However, obtaining the sequences and quantifying their expression is a challenge. In <jats:italic>Plasmodium falciparum<\/jats:italic>, the highly polymorphic <jats:italic>var<\/jats:italic> genes encode the major virulence protein, PfEMP1, which bind a range of human receptors through varying combinations of DBL and CIDR domains. Here we present a tool, Varia, to predict near full-length gene sequences and domain compositions of query genes from database genes sharing short sequence tags. Varia generates output through two complementary pipelines. Varia_VIP returns all putative gene sequences and domain compositions of the query gene from any partial sequence provided, thereby enabling experimental validation of specific genes of interest and detailed assessment of their putative domain structure. Varia_GEM accommodates rapid profiling of\u00a0<jats:italic>var<\/jats:italic>\u00a0gene expression in complex patient samples from DBL\u03b1 expression sequence tags (EST), by computing a sample overall transcript profile stratified by PfEMP1 domain types.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Varia_VIP was tested querying sequence tags from all DBL domain types using different search criteria. On average 92% of query tags had one or more 99% identical database hits, resulting in the full-length query gene sequence being identified (&gt;\u200999% identical DNA\u2009&gt;\u200980% of query gene) among the five most prominent database hits, for\u2009~\u200933% of the query genes. Optimized Varia_GEM settings allowed correct prediction of\u2009&gt;\u200990% of domains placed among the four most N-terminal domains, including the DBL\u03b1 domain, and\u2009&gt;\u200970% of C-terminal domains. With this accuracy, N-terminal domains could be predicted for\u2009&gt;\u200980% of queries, whereas prediction rates of C-terminal domains dropped with the distance from the DBL\u03b1 from 70 to 40%.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Prediction of <jats:italic>var<\/jats:italic> sequence and domain composition is possible from short sequence tags. Varia can be used to guide experimental validation of PfEMP1 sequences of interest and conduct high-throughput analysis of <jats:italic>var<\/jats:italic> type expression in patient samples.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-022-04573-6","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T13:10:05Z","timestamp":1643029805000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Varia: a tool for prediction, analysis and visualisation of variable genes"],"prefix":"10.1186","volume":"23","author":[{"given":"Gavin","family":"Mackenzie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasmus W.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Lavstsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1246-7404","authenticated-orcid":false,"given":"Thomas D.","family":"Otto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"issue":"Suppl 1","key":"4573_CR1","doi-asserted-by":"publisher","first-page":"S57","DOI":"10.1017\/S0031182014001528","volume":"142","author":"AJ Reid","year":"2015","unstructured":"Reid AJ. Large, rapidly evolving gene families are at the forefront of host-parasite interactions in Apicomplexa. Parasitology. 2015;142(Suppl 1):S57-70.","journal-title":"Parasitology"},{"issue":"1","key":"4573_CR2","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1111\/imr.12807","volume":"293","author":"AR Jensen","year":"2020","unstructured":"Jensen AR, Adams Y, Hviid L. Cerebral Plasmodium falciparum malaria: the role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it. Immunol Rev. 2020;293(1):230\u201352.","journal-title":"Immunol Rev"},{"key":"4573_CR3","doi-asserted-by":"publisher","first-page":"52","DOI":"10.12688\/wellcomeopenres.14571.1","volume":"3","author":"TD Otto","year":"2018","unstructured":"Otto TD, Bohme U, Sanders M, Reid A, Bruske EI, Duffy CW, Bull PC, Pearson RD, Abdi A, Dimonte S, et al. Long read assemblies of geographically dispersed Plasmodium falciparum isolates reveal highly structured subtelomeres. 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Cell Host Microbe. 2017;22(5):601\u2013614.","DOI":"10.1016\/j.chom.2017.09.009"},{"key":"4573_CR14","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/1471-2148-13-110","volume":"13","author":"MM Zilversmit","year":"2013","unstructured":"Zilversmit MM, Chase EK, Chen DS, Awadalla P, Day KP, McVean G. Hypervariable antigen genes in malaria have ancient roots. BMC Evol Biol. 2013;13:110.","journal-title":"BMC Evol Biol"},{"issue":"26","key":"4573_CR15","doi-asserted-by":"publisher","first-page":"E1791","DOI":"10.1073\/pnas.1120455109","volume":"109","author":"T Lavstsen","year":"2012","unstructured":"Lavstsen T, Turner L, Saguti F, Magistrado P, Rask TS, Jespersen JS, Wang CW, Berger SS, Baraka V, Marquard AM, et al. Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children. Proc Natl Acad Sci USA. 2012;109(26):E1791-1800.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"4573_CR16","doi-asserted-by":"publisher","first-page":"3282","DOI":"10.1038\/s41598-018-21591-8","volume":"8","author":"E Carrington","year":"2018","unstructured":"Carrington E, Otto TD, Szestak T, Lennartz F, Higgins MK, Newbold CI, Craig AG. In silico guided reconstruction and analysis of ICAM-1-binding var genes from Plasmodium falciparum. Sci Rep. 2018;8(1):3282.","journal-title":"Sci Rep"},{"key":"4573_CR17","doi-asserted-by":"crossref","unstructured":"Wichers JS, Tonkin-Hill G, Thye T, Krumkamp R, Kreuels B, Strauss J, von Thien H, Scholz JA, Smedegaard Hansson H, Weisel Jensen R et al. Common virulence gene expression in adult first-time infected malaria patients and severe cases. 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