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New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali
BACKGROUND: Encoded by the var gene family, highly variable Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) proteins mediate tissue-specific cytoadherence of infected erythrocytes, resulting in immune evasion and severe malaria disease. Sequencing and assembling the 40–60 var gene comp...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368897/ https://www.ncbi.nlm.nih.gov/pubmed/28351419 http://dx.doi.org/10.1186/s13073-017-0422-4 |
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author | Dara, Antoine Drábek, Elliott F. Travassos, Mark A. Moser, Kara A. Delcher, Arthur L. Su, Qi Hostelley, Timothy Coulibaly, Drissa Daou, Modibo Dembele, Ahmadou Diarra, Issa Kone, Abdoulaye K. Kouriba, Bourema Laurens, Matthew B. Niangaly, Amadou Traore, Karim Tolo, Youssouf Fraser, Claire M. Thera, Mahamadou A. Djimde, Abdoulaye A. Doumbo, Ogobara K. Plowe, Christopher V. Silva, Joana C. |
author_facet | Dara, Antoine Drábek, Elliott F. Travassos, Mark A. Moser, Kara A. Delcher, Arthur L. Su, Qi Hostelley, Timothy Coulibaly, Drissa Daou, Modibo Dembele, Ahmadou Diarra, Issa Kone, Abdoulaye K. Kouriba, Bourema Laurens, Matthew B. Niangaly, Amadou Traore, Karim Tolo, Youssouf Fraser, Claire M. Thera, Mahamadou A. Djimde, Abdoulaye A. Doumbo, Ogobara K. Plowe, Christopher V. Silva, Joana C. |
author_sort | Dara, Antoine |
collection | PubMed |
description | BACKGROUND: Encoded by the var gene family, highly variable Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) proteins mediate tissue-specific cytoadherence of infected erythrocytes, resulting in immune evasion and severe malaria disease. Sequencing and assembling the 40–60 var gene complement for individual infections has been notoriously difficult, impeding molecular epidemiological studies and the assessment of particular var elements as subunit vaccine candidates. METHODS: We developed and validated a novel algorithm, Exon-Targeted Hybrid Assembly (ETHA), to perform targeted assembly of var gene sequences, based on a combination of Pacific Biosciences and Illumina data. RESULTS: Using ETHA, we characterized the repertoire of var genes in 12 samples from uncomplicated malaria infections in children from a single Malian village and showed them to be as genetically diverse as vars from isolates from around the globe. The gene var2csa, a member of the var family associated with placental malaria pathogenesis, was present in each genome, as were vars previously associated with severe malaria. CONCLUSION: ETHA, a tool to discover novel var sequences from clinical samples, will aid the understanding of malaria pathogenesis and inform the design of malaria vaccines based on PfEMP1. ETHA is available at: https://sourceforge.net/projects/etha/. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-017-0422-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5368897 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53688972017-03-30 New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali Dara, Antoine Drábek, Elliott F. Travassos, Mark A. Moser, Kara A. Delcher, Arthur L. Su, Qi Hostelley, Timothy Coulibaly, Drissa Daou, Modibo Dembele, Ahmadou Diarra, Issa Kone, Abdoulaye K. Kouriba, Bourema Laurens, Matthew B. Niangaly, Amadou Traore, Karim Tolo, Youssouf Fraser, Claire M. Thera, Mahamadou A. Djimde, Abdoulaye A. Doumbo, Ogobara K. Plowe, Christopher V. Silva, Joana C. Genome Med Research BACKGROUND: Encoded by the var gene family, highly variable Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) proteins mediate tissue-specific cytoadherence of infected erythrocytes, resulting in immune evasion and severe malaria disease. Sequencing and assembling the 40–60 var gene complement for individual infections has been notoriously difficult, impeding molecular epidemiological studies and the assessment of particular var elements as subunit vaccine candidates. METHODS: We developed and validated a novel algorithm, Exon-Targeted Hybrid Assembly (ETHA), to perform targeted assembly of var gene sequences, based on a combination of Pacific Biosciences and Illumina data. RESULTS: Using ETHA, we characterized the repertoire of var genes in 12 samples from uncomplicated malaria infections in children from a single Malian village and showed them to be as genetically diverse as vars from isolates from around the globe. The gene var2csa, a member of the var family associated with placental malaria pathogenesis, was present in each genome, as were vars previously associated with severe malaria. CONCLUSION: ETHA, a tool to discover novel var sequences from clinical samples, will aid the understanding of malaria pathogenesis and inform the design of malaria vaccines based on PfEMP1. ETHA is available at: https://sourceforge.net/projects/etha/. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-017-0422-4) contains supplementary material, which is available to authorized users. BioMed Central 2017-03-28 /pmc/articles/PMC5368897/ /pubmed/28351419 http://dx.doi.org/10.1186/s13073-017-0422-4 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Dara, Antoine Drábek, Elliott F. Travassos, Mark A. Moser, Kara A. Delcher, Arthur L. Su, Qi Hostelley, Timothy Coulibaly, Drissa Daou, Modibo Dembele, Ahmadou Diarra, Issa Kone, Abdoulaye K. Kouriba, Bourema Laurens, Matthew B. Niangaly, Amadou Traore, Karim Tolo, Youssouf Fraser, Claire M. Thera, Mahamadou A. Djimde, Abdoulaye A. Doumbo, Ogobara K. Plowe, Christopher V. Silva, Joana C. New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali |
title | New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali |
title_full | New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali |
title_fullStr | New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali |
title_full_unstemmed | New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali |
title_short | New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali |
title_sort | new var reconstruction algorithm exposes high var sequence diversity in a single geographic location in mali |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368897/ https://www.ncbi.nlm.nih.gov/pubmed/28351419 http://dx.doi.org/10.1186/s13073-017-0422-4 |
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