Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing

Magnus Manske; Olivo Miotto; Susana Campino; Sarah Auburn; Jacob Almagro-Garcia; Gareth Maslen; Jack O'Brien; Abdoulaye Djimde; Ogobara Doumbo; Issaka Zongo; Jean Bosco Ouedraogo; Pascal Michon; Ivo Mueller; Peter Siba; Alexis Nzila; Steffen Borrmann; Steven M. Kiara; Kevin Marsh; Hongying Jiang; Xin Zhuan Su; Chanaki Amaratunga; Rick Fairhurst; Duong Socheat; Francois Nosten; Mallika Imwong; Nicholas J. White; Mandy Sanders; Elisa Anastasi; Dan Alcock; Eleanor Drury; Samuel Oyola; Michael A. Quail; Daniel J. Turner; Valentin Ruano-Rubio; Dushyanth Jyothi; Lucas Amenga-Etego; Christina Hubbart; Anna Jeffreys; Kate Rowlands; Colin Sutherland; Cally Roper; Valentina Mangano; David Modiano; John C. Tan; Michael T. Ferdig; Alfred Amambua-Ngwa; David J. Conway; Shannon Takala-Harrison; Christopher V. Plowe; Julian C. Rayner; Kirk A. Rockett; Taane G. Clark; Chris I. Newbold; Matthew Berriman; Bronwyn MacInnis; Dominic P. Kwiatkowski

doi:10.1038/nature11174

Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing

Magnus Manske, Olivo Miotto, Susana Campino, Sarah Auburn, Jacob Almagro-Garcia, Gareth Maslen, Jack O'Brien, Abdoulaye Djimde, Ogobara Doumbo, Issaka Zongo, Jean Bosco Ouedraogo, Pascal Michon, Ivo Mueller, Peter Siba, Alexis Nzila, Steffen Borrmann, Steven M. Kiara, Kevin Marsh, Hongying Jiang, Xin Zhuan SuChanaki Amaratunga, Rick Fairhurst, Duong Socheat, Francois Nosten, Mallika Imwong, Nicholas J. White, Mandy Sanders, Elisa Anastasi, Dan Alcock, Eleanor Drury, Samuel Oyola, Michael A. Quail, Daniel J. Turner, Valentin Ruano-Rubio, Dushyanth Jyothi, Lucas Amenga-Etego, Christina Hubbart, Anna Jeffreys, Kate Rowlands, Colin Sutherland, Cally Roper, Valentina Mangano, David Modiano, John C. Tan, Michael T. Ferdig, Alfred Amambua-Ngwa, David J. Conway, Shannon Takala-Harrison, Christopher V. Plowe, Julian C. Rayner, Kirk A. Rockett, Taane G. Clark, Chris I. Newbold, Matthew Berriman, Bronwyn MacInnis, Dominic P. Kwiatkowski^*

^*Corresponding author for this work

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

401 Scopus citations

Abstract

Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P.falciparum genome.

Original language	English
Pages (from-to)	375-379
Number of pages	5
Journal	Nature
Volume	487
Issue number	7407
DOIs	https://doi.org/10.1038/nature11174
State	Published - 19 Jul 2012
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgements We thank G. Dougan and N. Day for support, and T. Anderson and M. Mackinnon for comments. The sequencing and analysis components of this study were supported by the Wellcome Trust through Sanger Institute core funding (077012/Z/05/Z; 098051) and a Strategic Award (090770/Z/09/Z); the Medical Research Council (MRC) through the MRC Centre for Genomics and Global Health (G0600718) and an MRC Professorship to D.P.K. (G19/9). Other parts of this study were partly supported by the Wellcome Trust including core support to the Wellcome Trust Centre for Human Genetics (075491/Z/04; 090532/Z/09/Z); the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; and a Howard Hughes Medical Institute International Scholarship (55005502) to A.D.

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Manske, M., Miotto, O., Campino, S., Auburn, S., Almagro-Garcia, J., Maslen, G., O'Brien, J., Djimde, A., Doumbo, O., Zongo, I., Ouedraogo, J. B., Michon, P., Mueller, I., Siba, P., Nzila, A., Borrmann, S., Kiara, S. M., Marsh, K., Jiang, H., ... Kwiatkowski, D. P. (2012). Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing. Nature, 487(7407), 375-379. https://doi.org/10.1038/nature11174

@article{d87868bad9d34d6e88408f5678c60c6f,

title = "Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing",

abstract = "Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P.falciparum genome.",

author = "Magnus Manske and Olivo Miotto and Susana Campino and Sarah Auburn and Jacob Almagro-Garcia and Gareth Maslen and Jack O'Brien and Abdoulaye Djimde and Ogobara Doumbo and Issaka Zongo and Ouedraogo, \{Jean Bosco\} and Pascal Michon and Ivo Mueller and Peter Siba and Alexis Nzila and Steffen Borrmann and Kiara, \{Steven M.\} and Kevin Marsh and Hongying Jiang and Su, \{Xin Zhuan\} and Chanaki Amaratunga and Rick Fairhurst and Duong Socheat and Francois Nosten and Mallika Imwong and White, \{Nicholas J.\} and Mandy Sanders and Elisa Anastasi and Dan Alcock and Eleanor Drury and Samuel Oyola and Quail, \{Michael A.\} and Turner, \{Daniel J.\} and Valentin Ruano-Rubio and Dushyanth Jyothi and Lucas Amenga-Etego and Christina Hubbart and Anna Jeffreys and Kate Rowlands and Colin Sutherland and Cally Roper and Valentina Mangano and David Modiano and Tan, \{John C.\} and Ferdig, \{Michael T.\} and Alfred Amambua-Ngwa and Conway, \{David J.\} and Shannon Takala-Harrison and Plowe, \{Christopher V.\} and Rayner, \{Julian C.\} and Rockett, \{Kirk A.\} and Clark, \{Taane G.\} and Newbold, \{Chris I.\} and Matthew Berriman and Bronwyn MacInnis and Kwiatkowski, \{Dominic P.\}",

note = "Funding Information: Acknowledgements We thank G. Dougan and N. Day for support, and T. Anderson and M. Mackinnon for comments. The sequencing and analysis components of this study were supported by the Wellcome Trust through Sanger Institute core funding (077012/Z/05/Z; 098051) and a Strategic Award (090770/Z/09/Z); the Medical Research Council (MRC) through the MRC Centre for Genomics and Global Health (G0600718) and an MRC Professorship to D.P.K. (G19/9). Other parts of this study were partly supported by the Wellcome Trust including core support to the Wellcome Trust Centre for Human Genetics (075491/Z/04; 090532/Z/09/Z); the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; and a Howard Hughes Medical Institute International Scholarship (55005502) to A.D.",

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doi = "10.1038/nature11174",

language = "English",

volume = "487",

pages = "375--379",

journal = "Nature",

issn = "0028-0836",

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Manske, M, Miotto, O, Campino, S, Auburn, S, Almagro-Garcia, J, Maslen, G, O'Brien, J, Djimde, A, Doumbo, O, Zongo, I, Ouedraogo, JB, Michon, P, Mueller, I, Siba, P, Nzila, A, Borrmann, S, Kiara, SM, Marsh, K, Jiang, H, Su, XZ, Amaratunga, C, Fairhurst, R, Socheat, D, Nosten, F, Imwong, M, White, NJ, Sanders, M, Anastasi, E, Alcock, D, Drury, E, Oyola, S, Quail, MA, Turner, DJ, Ruano-Rubio, V, Jyothi, D, Amenga-Etego, L, Hubbart, C, Jeffreys, A, Rowlands, K, Sutherland, C, Roper, C, Mangano, V, Modiano, D, Tan, JC, Ferdig, MT, Amambua-Ngwa, A, Conway, DJ, Takala-Harrison, S, Plowe, CV, Rayner, JC, Rockett, KA, Clark, TG, Newbold, CI, Berriman, M, MacInnis, B & Kwiatkowski, DP 2012, 'Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing', Nature, vol. 487, no. 7407, pp. 375-379. https://doi.org/10.1038/nature11174

TY - JOUR

T1 - Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing

AU - Manske, Magnus

AU - Miotto, Olivo

AU - Campino, Susana

AU - Auburn, Sarah

AU - Almagro-Garcia, Jacob

AU - Maslen, Gareth

AU - O'Brien, Jack

AU - Djimde, Abdoulaye

AU - Doumbo, Ogobara

AU - Zongo, Issaka

AU - Ouedraogo, Jean Bosco

AU - Michon, Pascal

AU - Mueller, Ivo

AU - Siba, Peter

AU - Nzila, Alexis

AU - Borrmann, Steffen

AU - Kiara, Steven M.

AU - Marsh, Kevin

AU - Jiang, Hongying

AU - Su, Xin Zhuan

AU - Amaratunga, Chanaki

AU - Fairhurst, Rick

AU - Socheat, Duong

AU - Nosten, Francois

AU - Imwong, Mallika

AU - White, Nicholas J.

AU - Sanders, Mandy

AU - Anastasi, Elisa

AU - Alcock, Dan

AU - Drury, Eleanor

AU - Oyola, Samuel

AU - Quail, Michael A.

AU - Turner, Daniel J.

AU - Ruano-Rubio, Valentin

AU - Jyothi, Dushyanth

AU - Amenga-Etego, Lucas

AU - Hubbart, Christina

AU - Jeffreys, Anna

AU - Rowlands, Kate

AU - Sutherland, Colin

AU - Roper, Cally

AU - Mangano, Valentina

AU - Modiano, David

AU - Tan, John C.

AU - Ferdig, Michael T.

AU - Amambua-Ngwa, Alfred

AU - Conway, David J.

AU - Takala-Harrison, Shannon

AU - Plowe, Christopher V.

AU - Rayner, Julian C.

AU - Rockett, Kirk A.

AU - Clark, Taane G.

AU - Newbold, Chris I.

AU - Berriman, Matthew

AU - MacInnis, Bronwyn

AU - Kwiatkowski, Dominic P.

N1 - Funding Information: Acknowledgements We thank G. Dougan and N. Day for support, and T. Anderson and M. Mackinnon for comments. The sequencing and analysis components of this study were supported by the Wellcome Trust through Sanger Institute core funding (077012/Z/05/Z; 098051) and a Strategic Award (090770/Z/09/Z); the Medical Research Council (MRC) through the MRC Centre for Genomics and Global Health (G0600718) and an MRC Professorship to D.P.K. (G19/9). Other parts of this study were partly supported by the Wellcome Trust including core support to the Wellcome Trust Centre for Human Genetics (075491/Z/04; 090532/Z/09/Z); the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; and a Howard Hughes Medical Institute International Scholarship (55005502) to A.D.

PY - 2012/7/19

Y1 - 2012/7/19

N2 - Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P.falciparum genome.

AB - Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P.falciparum genome.

UR - https://www.scopus.com/pages/publications/84863982076

U2 - 10.1038/nature11174

DO - 10.1038/nature11174

M3 - Article

C2 - 22722859

AN - SCOPUS:84863982076

SN - 0028-0836

VL - 487

SP - 375

EP - 379

JO - Nature

JF - Nature

IS - 7407

ER -

Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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