Differentiating Plasmodium Falciparum Alleles By Transforming Cartesian X,y Data To Polar Coordinates

Title:
Differentiating Plasmodium Falciparum Alleles By Transforming Cartesian X,y Data To Polar Coordinates
Authors:
DaRe, Jeana T.; Kouri, Drew P.; Zimmerman, Peter A.; Thomas, Peter J.
Abstract:
Background: Diagnosis of infectious diseases now benefits from advancing technology to perform multiplex analysis of a growing number of variables. These advances enable simultaneous surveillance of markers characterizing species and strain complexity, mutations associated with drug susceptibility, and antigen-based polymorphisms in relation to evaluation of vaccine effectiveness. We have recently developed assays detecting single nucleotide polymorphisms (SNPs) in the P. falciparum genome that take advantage of post-PCR ligation detection reaction and fluorescent microsphere labeling strategies. Data from these assays produce a spectrum of outcomes showing that infections result from single to multiple strains. Traditional methods for distinguishing true positive signal from background can cause false positive diagnoses leading to incorrect interpretation of outcomes associated with disease treatment. Results: Following analysis of Plasmodium falciparum dihydrofolate reductase SNPs associated with resistance to a commonly used antimalarial drug, Fansidar (Sulfadoxine/pyrimethamine), and presumably neutral SNPs for parasite strain differentiation, we first evaluated our data after setting a background signal based on the mean plus three standard deviations for known negative control samples. Our analysis of single allelic controls suggested that background for the absent allele increased as the concentration of the target allele increased. To address this problem, we introduced a simple change of variables from customary (X,Y) (Cartesian) coordinates to planar polar coordinates (X = rcos(theta), Y = rsin(theta)). Classification of multidimensional fluorescence signals based on histograms of angular and radial data distributions proved more effective than classification based on Cartesian thresholds. Comparison with known diallelic dilution controls suggests that histogram-based classification is effective for major: minor allele concentration ratios as high as 10:1. Conclusion: We have observed that the diallelic SNP data resulting from analysis of P. falciparum mutations is more accurately diagnosed when a simple polar transform of the (X, Y) data into (r,theta)is used. The development of high through-put methods for genotyping P. falciparum SNPs and the refinement of analytical approaches for evaluating these molecular diagnostic results significantly advance the evaluation of parasite population diversity and antimalarial drug resistance.
Citation:
DaRe, Jeana T., Drew P. Kouri, Peter A. Zimmerman, and Peter J. Thomas. 2010. "Differentiating Plasmodium Falciparum Alleles By Transforming Cartesian X,y Data To Polar Coordinates." Bmc Genetics 11: 57.
Publisher:
Biomed Central Ltd.
DATE ISSUED:
2010-06
Department:
Neuroscience
Type:
article
PUBLISHED VERSION:
10.1186/1471-2156-11-57
PERMANENT LINK:
http://hdl.handle.net/11282/309947

Full metadata record

DC FieldValue Language
dc.contributor.authorDaRe, Jeana T.en_US
dc.contributor.authorKouri, Drew P.en_US
dc.contributor.authorZimmerman, Peter A.en_US
dc.contributor.authorThomas, Peter J.en_US
dc.date.accessioned2013-12-23T16:21:49Z-
dc.date.available2013-12-23T16:21:49Z-
dc.date.issued2010-06en
dc.identifier.citationDaRe, Jeana T., Drew P. Kouri, Peter A. Zimmerman, and Peter J. Thomas. 2010. "Differentiating Plasmodium Falciparum Alleles By Transforming Cartesian X,y Data To Polar Coordinates." Bmc Genetics 11: 57.en_US
dc.identifier.issn1471-2156en_US
dc.identifier.urihttp://hdl.handle.net/11282/309947-
dc.description.abstractBackground: Diagnosis of infectious diseases now benefits from advancing technology to perform multiplex analysis of a growing number of variables. These advances enable simultaneous surveillance of markers characterizing species and strain complexity, mutations associated with drug susceptibility, and antigen-based polymorphisms in relation to evaluation of vaccine effectiveness. We have recently developed assays detecting single nucleotide polymorphisms (SNPs) in the P. falciparum genome that take advantage of post-PCR ligation detection reaction and fluorescent microsphere labeling strategies. Data from these assays produce a spectrum of outcomes showing that infections result from single to multiple strains. Traditional methods for distinguishing true positive signal from background can cause false positive diagnoses leading to incorrect interpretation of outcomes associated with disease treatment. Results: Following analysis of Plasmodium falciparum dihydrofolate reductase SNPs associated with resistance to a commonly used antimalarial drug, Fansidar (Sulfadoxine/pyrimethamine), and presumably neutral SNPs for parasite strain differentiation, we first evaluated our data after setting a background signal based on the mean plus three standard deviations for known negative control samples. Our analysis of single allelic controls suggested that background for the absent allele increased as the concentration of the target allele increased. To address this problem, we introduced a simple change of variables from customary (X,Y) (Cartesian) coordinates to planar polar coordinates (X = rcos(theta), Y = rsin(theta)). Classification of multidimensional fluorescence signals based on histograms of angular and radial data distributions proved more effective than classification based on Cartesian thresholds. Comparison with known diallelic dilution controls suggests that histogram-based classification is effective for major: minor allele concentration ratios as high as 10:1. Conclusion: We have observed that the diallelic SNP data resulting from analysis of P. falciparum mutations is more accurately diagnosed when a simple polar transform of the (X, Y) data into (r,theta)is used. The development of high through-put methods for genotyping P. falciparum SNPs and the refinement of analytical approaches for evaluating these molecular diagnostic results significantly advance the evaluation of parasite population diversity and antimalarial drug resistance.en_US
dc.language.isoen_USen_US
dc.publisherBiomed Central Ltd.en_US
dc.identifier.doi10.1186/1471-2156-11-57-
dc.subject.departmentNeuroscienceen_US
dc.titleDifferentiating Plasmodium Falciparum Alleles By Transforming Cartesian X,y Data To Polar Coordinatesen_US
dc.typearticleen_US
dc.identifier.journalBmc Geneticsen_US
dc.subject.keywordPapua New Guineaen_US
dc.subject.keywordMalariaen_US
dc.subject.keywordResistanceen_US
dc.subject.keywordAssayen_US
dc.subject.keywordPCRen_US
dc.subject.keywordHybridizationen_US
dc.subject.keywordPyrimethamineen_US
dc.subject.keywordMutationsen_US
dc.subject.keywordInfectionen_US
dc.subject.keywordImpacten_US
dc.subject.keywordGenetics & heredityen_US
dc.identifier.volume11en_US
dc.identifier.startpage57en_US
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