New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali
Abstract 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 g...
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| Format: | Article |
| Language: | English |
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BMC
2017-03-01
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| Series: | Genome Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s13073-017-0422-4 |
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doaj-570b0337c20f4df39b58ccd1d658a457 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Antoine Dara Elliott F. Drábek Mark A. Travassos Kara A. Moser Arthur L. Delcher Qi Su Timothy Hostelley Drissa Coulibaly Modibo Daou Ahmadou Dembele Issa Diarra Abdoulaye K. Kone Bourema Kouriba Matthew B. Laurens Amadou Niangaly Karim Traore Youssouf Tolo Claire M. Fraser Mahamadou A. Thera Abdoulaye A. Djimde Ogobara K. Doumbo Christopher V. Plowe Joana C. Silva |
| spellingShingle |
Antoine Dara Elliott F. Drábek Mark A. Travassos Kara A. Moser Arthur L. Delcher Qi Su Timothy Hostelley Drissa Coulibaly Modibo Daou Ahmadou Dembele Issa Diarra Abdoulaye K. Kone Bourema Kouriba Matthew B. Laurens Amadou Niangaly Karim Traore Youssouf Tolo Claire M. Fraser Mahamadou A. Thera Abdoulaye A. Djimde Ogobara K. Doumbo Christopher V. Plowe Joana C. Silva New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali Genome Medicine Malaria Plasmodium falciparum Plasmodium falciparum erythrocyte membrane protein-1 PfEMP1 var var2csa |
| author_facet |
Antoine Dara Elliott F. Drábek Mark A. Travassos Kara A. Moser Arthur L. Delcher Qi Su Timothy Hostelley Drissa Coulibaly Modibo Daou Ahmadou Dembele Issa Diarra Abdoulaye K. Kone Bourema Kouriba Matthew B. Laurens Amadou Niangaly Karim Traore Youssouf Tolo Claire M. Fraser Mahamadou A. Thera Abdoulaye A. Djimde Ogobara K. Doumbo Christopher V. Plowe Joana C. Silva |
| author_sort |
Antoine Dara |
| title |
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_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_sort |
new var reconstruction algorithm exposes high var sequence diversity in a single geographic location in mali |
| publisher |
BMC |
| series |
Genome Medicine |
| issn |
1756-994X |
| publishDate |
2017-03-01 |
| description |
Abstract 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/ . |
| topic |
Malaria Plasmodium falciparum Plasmodium falciparum erythrocyte membrane protein-1 PfEMP1 var var2csa |
| url |
http://link.springer.com/article/10.1186/s13073-017-0422-4 |
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doaj-570b0337c20f4df39b58ccd1d658a4572020-11-25T00:27:52ZengBMCGenome Medicine1756-994X2017-03-019111410.1186/s13073-017-0422-4New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in MaliAntoine Dara0Elliott F. Drábek1Mark A. Travassos2Kara A. Moser3Arthur L. Delcher4Qi Su5Timothy Hostelley6Drissa Coulibaly7Modibo Daou8Ahmadou Dembele9Issa Diarra10Abdoulaye K. Kone11Bourema Kouriba12Matthew B. Laurens13Amadou Niangaly14Karim Traore15Youssouf Tolo16Claire M. Fraser17Mahamadou A. Thera18Abdoulaye A. Djimde19Ogobara K. Doumbo20Christopher V. Plowe21Joana C. Silva22Division of Malaria Research, Institute for Global Health, University of Maryland School of MedicineInstitute for Genome Sciences, University of Maryland School of MedicineDivision of Malaria Research, Institute for Global Health, University of Maryland School of MedicineInstitute for Genome Sciences, University of Maryland School of MedicineInstitute for Genome Sciences, University of Maryland School of MedicineInstitute for Genome Sciences, University of Maryland School of MedicineInstitute for Genome Sciences, University of Maryland School of MedicineMalaria Research and Training Center, University of Science, Techniques and TechnologiesMalaria Research and Training Center, University of Science, Techniques and TechnologiesMalaria Research and Training Center, University of Science, Techniques and TechnologiesMalaria Research and Training Center, University of Science, Techniques and TechnologiesMalaria Research and Training Center, University of Science, Techniques and TechnologiesMalaria Research and Training Center, University of Science, Techniques and TechnologiesDivision of Malaria Research, Institute for Global Health, University of Maryland School of MedicineMalaria Research and Training Center, University of Science, Techniques and TechnologiesMalaria Research and Training Center, University of Science, Techniques and TechnologiesMalaria Research and Training Center, University of Science, Techniques and TechnologiesInstitute for Genome Sciences, University of Maryland School of MedicineMalaria Research and Training Center, University of Science, Techniques and TechnologiesMalaria Research and Training Center, University of Science, Techniques and TechnologiesMalaria Research and Training Center, University of Science, Techniques and TechnologiesDivision of Malaria Research, Institute for Global Health, University of Maryland School of MedicineInstitute for Genome Sciences, University of Maryland School of MedicineAbstract 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/ .http://link.springer.com/article/10.1186/s13073-017-0422-4MalariaPlasmodium falciparumPlasmodium falciparum erythrocyte membrane protein-1PfEMP1varvar2csa |