title: FlexiChip package: an universal microarray with a dedicated analysis software for high-thoughput SNPs detection linked to anti-malarial drug resistance.
abstract: BACKGROUND
  A number of molecular tools have been developed to monitor the emergence and spread of anti-malarial drug resistance to Plasmodium falciparum. One of the major obstacles to the wider implementation of these tools is the absence of practical methods enabling high throughput analysis. Here a new Zip-code array is described, called FlexiChip, linked to a dedicated software program, which largely overcomes this problem.
  
  
  METHODS
  Previously published microarray probes detecting single-nucleotide polymorphisms (SNP) associated with parasite resistance to anti-malarial drugs (ResMalChip) were adapted for a universal microarray FlexiChip format. To evaluate the overall sensitivity of the FlexiChip package (microarray + software), the results of FlexiChip were compared to ResMalChip microarray, using the same extension probes and with the same PCR products. In both cases, sequence results were used as gold standard to calculate sensitivity and specificity. FlexiChip results obtained with a set of field isolates were then compared to those assessed in an independent reference laboratory.
  
  
  RESULTS
  The FlexiChip package gave results identical to the ResMalChip results in 92.7% of samples (kappa coefficient 0.8491, with a standard error 0.021) and had a sensitivity of 95.88% and a specificity of 97.68% compared to the sequencing as the reference method. Moreover the method performed well compared to the results obtained in the reference laboratories, with 99.7% of identical results (kappa coefficient 0.9923, S.E. 0.0523).
  
  
  CONCLUSIONS
  Microarrays could be employed to monitor P. falciparum drug resistance markers with greater cost effectiveness and the possibility for high throughput analysis. The FlexiChip package is a promising tool for use in poor resource settings of malaria endemic countries.
authors.affiliation: Laboratoire d'épidémiologie moléculaire, Institut Pasteur du Cambodge, 5 bd Monivong, BP 983, Phnom Penh, Cambodia. nicolas@pasteur-kh.org
authors.forename: Nicolas
authors.initials: N
authors.lastname: Steenkeste
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Dillies
authors.forename: Nimol
authors.initials: N
authors.lastname: Khim
authors.forename: Odile
authors.initials: O
authors.lastname: Sismeiro
authors.forename: Sophy
authors.initials: S
authors.lastname: Chy
authors.forename: Pharath
authors.initials: P
authors.lastname: Lim
authors.forename: Andreas
authors.initials: A
authors.lastname: Crameri
authors.forename: Christiane
authors.initials: C
authors.lastname: Bouchier
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Beck
authors.forename: Mallika
authors.initials: M
authors.lastname: Imwong
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.forename: Duong
authors.initials: D
authors.lastname: Socheat
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Coppée
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ariey
mesh_terms: D000818:Animals; D004351:Drug Resistance; D006801:Humans; D008288:Malaria / Q000469:parasitology; D046228:Microarray Analysis / Q000379:methods*; D021261:Parasitic Sensitivity Tests / Q000379:methods*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity; D012984:Software