New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali

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

doi:10.1186/s13073-017-0422-4

New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali

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. DjimdeOgobara K. Doumbo, Christopher V. Plowe, Joana C. Silva

School of Medicine

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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/.

Original language	English (US)
Article number	30
Journal	Genome Medicine
Volume	9
Issue number	1
DOIs	https://doi.org/10.1186/s13073-017-0422-4
State	Published - Mar 28 2017

Keywords

ETHA
Malaria
Mali
PfEMP1
Plasmodium falciparum
Plasmodium falciparum erythrocyte membrane protein-1
var
var2csa

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics
Genetics(clinical)

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10.1186/s13073-017-0422-4

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Dara, A., Drábek, E. F., Travassos, M. A., Moser, K. A., Delcher, A. L., Su, Q., Hostelley, T., Coulibaly, D., Daou, M., Dembele, A., Diarra, I., Kone, A. K., Kouriba, B., Laurens, M. B., Niangaly, A., Traore, K., Tolo, Y., Fraser, C. M., Thera, M. A., ... Silva, J. C. (2017). New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali. Genome Medicine, 9(1), Article 30. https://doi.org/10.1186/s13073-017-0422-4

Dara, A, Drábek, EF, Travassos, MA, Moser, KA, Delcher, AL, Su, Q, Hostelley, T, Coulibaly, D, Daou, M, Dembele, A, Diarra, I, Kone, AK, Kouriba, B, Laurens, MB, Niangaly, A, Traore, K, Tolo, Y, Fraser, CM, Thera, MA, Djimde, AA, Doumbo, OK, Plowe, CV & Silva, JC 2017, 'New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali', Genome Medicine, vol. 9, no. 1, 30. https://doi.org/10.1186/s13073-017-0422-4

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title = "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 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/.",

keywords = "ETHA, Malaria, Mali, PfEMP1, Plasmodium falciparum, Plasmodium falciparum erythrocyte membrane protein-1, var, var2csa",

author = "Antoine Dara and Dr{\'a}bek, {Elliott F.} and Travassos, {Mark A.} and Moser, {Kara A.} and Delcher, {Arthur L.} and Qi Su and Timothy Hostelley and Drissa Coulibaly and Modibo Daou and Ahmadou Dembele and Issa Diarra and Kone, {Abdoulaye K.} and Bourema Kouriba and Laurens, {Matthew B.} and Amadou Niangaly and Karim Traore and Youssouf Tolo and Fraser, {Claire M.} and Thera, {Mahamadou A.} and Djimde, {Abdoulaye A.} and Doumbo, {Ogobara K.} and Plowe, {Christopher V.} and Silva, {Joana C.}",

note = "Funding Information: This work was supported by a cooperative agreement (U19AI065683) from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) (CVP); NIAID/NIH GSCID Contract # HHSN272200900009C (CMF, JCS, CVP, MAT); NIAID/NIH U19AI110820 (CMF, JCS, CVP); NIH grant D43TW001589 from the Fogarty International Center to AD; a Burroughs Wellcome Fund/ American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship to MAT, and an award to CVP from the Howard Hughes Medical Institute. The funding bodies had no role in the design of the study, in collection, analysis, and interpretation of data, or in writing the manuscript. Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = mar,

day = "28",

doi = "10.1186/s13073-017-0422-4",

language = "English (US)",

volume = "9",

journal = "Genome Medicine",

issn = "1756-994X",

publisher = "BioMed Central",

number = "1",

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TY - JOUR

T1 - New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali

AU - Dara, Antoine

AU - Drábek, Elliott F.

AU - Travassos, Mark A.

AU - Moser, Kara A.

AU - Delcher, Arthur L.

AU - Su, Qi

AU - Hostelley, Timothy

AU - Coulibaly, Drissa

AU - Daou, Modibo

AU - Dembele, Ahmadou

AU - Diarra, Issa

AU - Kone, Abdoulaye K.

AU - Kouriba, Bourema

AU - Laurens, Matthew B.

AU - Niangaly, Amadou

AU - Traore, Karim

AU - Tolo, Youssouf

AU - Fraser, Claire M.

AU - Thera, Mahamadou A.

AU - Djimde, Abdoulaye A.

AU - Doumbo, Ogobara K.

AU - Plowe, Christopher V.

AU - Silva, Joana C.

N1 - Funding Information: This work was supported by a cooperative agreement (U19AI065683) from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) (CVP); NIAID/NIH GSCID Contract # HHSN272200900009C (CMF, JCS, CVP, MAT); NIAID/NIH U19AI110820 (CMF, JCS, CVP); NIH grant D43TW001589 from the Fogarty International Center to AD; a Burroughs Wellcome Fund/ American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship to MAT, and an award to CVP from the Howard Hughes Medical Institute. The funding bodies had no role in the design of the study, in collection, analysis, and interpretation of data, or in writing the manuscript. Publisher Copyright: © 2017 The Author(s).

PY - 2017/3/28

Y1 - 2017/3/28

N2 - 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/.

AB - 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/.

KW - ETHA

KW - Malaria

KW - Mali

KW - PfEMP1

KW - Plasmodium falciparum

KW - Plasmodium falciparum erythrocyte membrane protein-1

KW - var

KW - var2csa

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DO - 10.1186/s13073-017-0422-4

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AN - SCOPUS:85016136194

SN - 1756-994X

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New var reconstruction algorithm exposes high var sequence diversity in a single geographic location in Mali

Abstract

Keywords

ASJC Scopus subject areas

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