An online mapping database of molecular markers of drug resistance in Plasmodium falciparum: the ACT Partner Drug Molecular Surveyor.


Journal

Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802

Informations de publication

Date de publication:
18 Jan 2019
Historique:
received: 20 11 2018
accepted: 10 01 2019
entrez: 20 1 2019
pubmed: 20 1 2019
medline: 8 2 2019
Statut: epublish

Résumé

Prior to this project, only a handful of online visualizations existed for exploring the published literature on molecular markers of antimalarial drug resistance, and none specifically for the markers associated with Plasmodium falciparum resistance to the partner drugs in artemisinin-based combination therapy (ACT). Molecular information is collected in studies with different designs, using a variety of molecular methodologies and data analysis strategies, making it difficult to compare across studies. The purpose of this project was to develop a free online tool, which visualizes the widely published data on molecular markers of antimalarial drug resistance, starting with the two genes pfcrt and pfmdr-1, associated with resistance to the three most common partner drugs; amodiaquine, lumefantrine and mefloquine. A literature review was conducted, and a standardized method was used to extract data from publications, and critical decisions on visualization were made. A global geospatial database was developed of specific pfmdr1 and pfcrt single nucleotide polymorphisms and pfmdr1 copy number variation. An informatics framework was developed that allowed flexibility in development of the tool over time and efficient adaptation to different source data. The database discussed in this paper has pfmdr1 and pfcrt marker prevalence information, from 579 geographic sites in 76 different countries, including results from over 86,000 samples from 456 articles published January 2001-May 2017. The ACT Partner Drugs Molecular Surveyor was launched by the WorldWide Antimalarial Resistance Network (WWARN) in March 2015 and it has attracted over 3000 unique visitors since then. Presented here is a demonstration of how the Surveyor database can be explored to monitor local, temporal changes in the prevalence of molecular markers. Here publications up to May 2017 were included, however the online ACT partner drug Molecular Surveyor is continuously updated with new data and relevant markers. The WWARN ACT Partner Drugs Molecular Surveyor summarizes data on resistance markers in the pfmdr1 and pfcrt genes. The database is fully accessible, providing users with a rich resource to explore and analyze, and thus utilize a centralized, standardized database for different purposes. This open-source software framework can be adapted to other data, as demonstrated by the subsequent launch of the Artemisinin Molecular Surveyor and the Vivax Surveyor.

Sections du résumé

BACKGROUND BACKGROUND
Prior to this project, only a handful of online visualizations existed for exploring the published literature on molecular markers of antimalarial drug resistance, and none specifically for the markers associated with Plasmodium falciparum resistance to the partner drugs in artemisinin-based combination therapy (ACT). Molecular information is collected in studies with different designs, using a variety of molecular methodologies and data analysis strategies, making it difficult to compare across studies. The purpose of this project was to develop a free online tool, which visualizes the widely published data on molecular markers of antimalarial drug resistance, starting with the two genes pfcrt and pfmdr-1, associated with resistance to the three most common partner drugs; amodiaquine, lumefantrine and mefloquine.
METHODS METHODS
A literature review was conducted, and a standardized method was used to extract data from publications, and critical decisions on visualization were made. A global geospatial database was developed of specific pfmdr1 and pfcrt single nucleotide polymorphisms and pfmdr1 copy number variation. An informatics framework was developed that allowed flexibility in development of the tool over time and efficient adaptation to different source data.
RESULTS RESULTS
The database discussed in this paper has pfmdr1 and pfcrt marker prevalence information, from 579 geographic sites in 76 different countries, including results from over 86,000 samples from 456 articles published January 2001-May 2017. The ACT Partner Drugs Molecular Surveyor was launched by the WorldWide Antimalarial Resistance Network (WWARN) in March 2015 and it has attracted over 3000 unique visitors since then. Presented here is a demonstration of how the Surveyor database can be explored to monitor local, temporal changes in the prevalence of molecular markers. Here publications up to May 2017 were included, however the online ACT partner drug Molecular Surveyor is continuously updated with new data and relevant markers.
CONCLUSIONS CONCLUSIONS
The WWARN ACT Partner Drugs Molecular Surveyor summarizes data on resistance markers in the pfmdr1 and pfcrt genes. The database is fully accessible, providing users with a rich resource to explore and analyze, and thus utilize a centralized, standardized database for different purposes. This open-source software framework can be adapted to other data, as demonstrated by the subsequent launch of the Artemisinin Molecular Surveyor and the Vivax Surveyor.

Identifiants

pubmed: 30658642
doi: 10.1186/s12936-019-2645-x
pii: 10.1186/s12936-019-2645-x
pmc: PMC6339428
doi:

Substances chimiques

Antimalarials 0
Mdr1 protein, Plasmodium falciparum 0
Membrane Transport Proteins 0
Multidrug Resistance-Associated Proteins 0
PfCRT protein, Plasmodium falciparum 0
Protozoan Proteins 0
Amodiaquine 220236ED28
Lumefantrine F38R0JR742
Mefloquine TML814419R

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

12

Subventions

Organisme : Exxon Mobil Foundation
ID : Charitable donation

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Auteurs

Sabina Dahlström Otienoburu (SD)

WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK.
Department of Computer Science and Engineering, Johnson C. Smith University, Charlotte, NC, USA.

Ignacio Suay (I)

WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK.

Steven Garcia (S)

WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK.

Nigel V Thomas (NV)

WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK.

Suttipat Srisutham (S)

Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

Anders Björkman (A)

Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Georgina S Humphreys (GS)

WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK. georginahumphreys@gmail.com.

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Classifications MeSH