FlexiChip package: an universal microarray with a dedicated analysis software for high-thoughput SNPs detection linked to anti-malarial drug resistance.

FlexiChip package: an universal microarray with a dedicated analysis software for high-thoughput SNPs detection linked to anti-malarial drug resistance.
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DOI:
10.1186/1475-2875-8-229
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发表时间:
2009-10-15
期刊:
影响因子:
3
通讯作者:
Ariey F
Ariey F
中科院分区:
医学3区
文献类型:
--
作者:
Steenkeste N;Dillies MA;Khim N;Sismeiro O;Chy S;Lim P;Crameri A;Bouchier C;Mercereau-Puijalon O;Beck HP;Imwong M;Dondorp AM;Socheat D;Rogier C;Coppée JY;Ariey F

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已经开发了一些分子工具来监测抗疟疾药物对恶性疟原虫的耐药性的出现和传播。这些工具广泛应用的主要障碍之一是缺乏实现高通量分析的实用方法。这里描述了一种新的邮政编码阵列,称为FlexiChip,与专用软件程序相连接,它在很大程度上克服了这个问题。先前发表的微阵列探针检测与寄生虫抗疟疾药物耐药性(ResMalChip)相关的单核苷酸多态性(SNP),适用于通用微阵列FlexiChip格式。为了评估FlexiChip封装(微阵列+软件)的整体灵敏度,使用相同的延伸探针和相同的PCR产物,将FlexiChip的结果与ResMalChip微阵列进行比较。在这两种情况下,序列结果作为计算灵敏度和特异性的金标准。然后将flexicchip结果与独立参考实验室评估的结果进行比较。FlexiChip封装在92.7%的样品中与ResMalChip结果相同(kappa系数0.8491,标准误差0.021),与测序作为参考方法相比,灵敏度为95.88%,特异性为97.68%。与参考实验室的结果相比,该方法具有良好的符合率,99.7% (kappa系数0.9923,标准差0.0523)。微阵列技术可用于恶性疟原虫耐药标记物的监测,具有较高的成本效益和高通量分析的可能性。在疟疾流行国家资源贫乏的环境中,柔性芯片是一种很有前途的工具。
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. 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. 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). 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.
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期刊: NATURE GENETICS
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DOI: 10.1186/1475-2875-5-34
发表时间: 2006-04-26
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影响因子: 3
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