Is High Resolution Melting Analysis (HRMA) Accurate for Detection of Human Disease-Associated Mutations? A Meta Analysis
Is High Resolution Melting Analysis (HRMA) Accurate for Detection of Human Disease-Associated Mutations? A Meta Analysis
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DOI：
10.1371/journal.pone.0028078
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发表时间：
2011-12-14
期刊：
影响因子：
3.7
通讯作者：
Xu, An-Gao
中科院分区：
文献类型：
--
作者：
Li, Bing-Sheng;Wang, Xin-Ying;Xu, An-Gao
背景：高分辨率熔融分析(HRMA)正成为突变检测的首选方法。然而，它在个人临床诊断环境中的准确性是可变的。为了评估HRMA与DNA测序在不同常规临床环境中诊断人类突变的准确性，我们对已发表的报告进行了荟萃分析。方法/主要研究结果：在最初搜索标准获得的195篇文献中，34篇评估HRMA准确性的研究纳入了荟萃分析。我们发现，HRMA是一种检测人类疾病相关突变的高度敏感的测试。总体敏感度为97.5%(95%可信区间：96.8-98.5；I-2=27.0%)。亚组分析显示对非HR-1工具的敏感性更高(敏感性98.7%(95%CI：97.7-99.3；I-2=0.0%))和合格样本量亚组(敏感性99.3%(95%CI：98.1-99.8；I-2=0.0%))。HRMA特异性在不同研究之间表现出相当大的异质性。该技术的灵敏度受样本量和仪器类型的影响，但不受样本源和染料类型的影响。结论/意义：这些结果表明，HRMA是一种检测人类疾病相关突变的高灵敏度、简单和低成本的检测方法，特别是对于突变发生率较低的样本。实施HRMA可以显著减轻DNA测序的负担，但应该认识到，其敏感性因有/无突变的样本数量而异，阳性结果需要DNA测序才能确认。
Background: High Resolution Melting Analysis (HRMA) is becoming the preferred method for mutation detection. However, its accuracy in the individual clinical diagnostic setting is variable. To assess the diagnostic accuracy of HRMA for human mutations in comparison to DNA sequencing in different routine clinical settings, we have conducted a meta-analysis of published reports.Methodology/Principal Findings: Out of 195 publications obtained from the initial search criteria, thirty-four studies assessing the accuracy of HRMA were included in the meta-analysis. We found that HRMA was a highly sensitive test for detecting disease-associated mutations in humans. Overall, the summary sensitivity was 97.5% (95% confidence interval (CI): 96.8-98.5; I-2 = 27.0%). Subgroup analysis showed even higher sensitivity for non-HR-1 instruments (sensitivity 98.7% (95% CI: 97.7-99.3; I-2 = 0.0%)) and an eligible sample size subgroup (sensitivity 99.3% (95% CI: 98.1-99.8; I-2 = 0.0%)). HRMA specificity showed considerable heterogeneity between studies. Sensitivity of the techniques was influenced by sample size and instrument type but by not sample source or dye type.Conclusions/Significance: These findings show that HRMA is a highly sensitive, simple and low-cost test to detect human disease-associated mutations, especially for samples with mutations of low incidence. The burden on DNA sequencing could be significantly reduced by the implementation of HRMA, but it should be recognized that its sensitivity varies according to the number of samples with/without mutations, and positive results require DNA sequencing for confirmation.