Place of concordance-discordance model in evaluating NGS performance.

IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY
Human Heredity Pub Date : 2024-03-16 DOI:10.1159/000538401
Yue Zhai, Claire Bardel, Maxime Vallée, Jean Iwaz, Pascal Roy
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引用次数: 0

Abstract

Introduction: Ideally, evaluating NGS performance requires a gold standard; in its absence, concordance between replicates is often used as substitute standard. However, the appropriateness of the concordance-discordance criterion has been rarely evaluated. This study analyzes the relationship between the probability of discordance and the probability of error under different conditions.

Methods: This study used a conditional probability approach under conditional dependence then conditional independence between two sequencing results and compares the probabilities of discordance and error in different theoretical conditions of sensitivity, specificity, and correlation between replicates, then on real results of sequencing genome NA12878. The study examines also covariate effects on discordance and error using generalized additive models with smooth functions.

Results: With 99% sensitivity and 99.9% specificity under conditional independence, the probability of error for a positive concordant pair of calls is 0.1%. With additional hypotheses of 0.1% prevalence and 0.9 correlation between replicates, the probability of error for a positive concordant pair is 47.4%. With real data, the estimated sensitivity, specificity, and correlation between tests for variants are around 98.98%, 99.996%, and 93%, respectively, and the error rate for positive concordant calls approximates 2.5%. In covariate effect analyses, the effects' functional form are close between discordance and error models, though the parts of deviance explained by the covariates differ between discordance and error models.

Conclusion: With conditional independence of two sequencing results, the concordance-discordance criterion seems acceptable as substitute standard. However, with high correlation, the criterion becomes questionable because a high percentage of false concordant results appears among concordant results.

一致性-不一致性模型在评估 NGS 性能中的地位。
导言:理想情况下,评估 NGS 性能需要一个金标准;在没有金标准的情况下,通常使用重复间的一致性作为替代标准。然而,人们很少评估一致性-不一致性标准是否合适。本研究分析了不同条件下不一致概率与误差概率之间的关系:本研究采用条件概率法,在两个测序结果之间先有条件依赖后有条件独立的情况下,比较了在灵敏度、特异性和重复序列间相关性等不同理论条件下的不一致概率和错误概率,然后对基因组 NA12878 的实际测序结果进行了比较。该研究还使用具有平滑函数的广义加法模型研究了协变量对不一致性和误差的影响:在条件独立的情况下,灵敏度为 99%,特异度为 99.9%,一对阳性一致调用的错误概率为 0.1%。在流行率为 0.1%、重复间相关性为 0.9 的附加假设下,一对阳性一致呼叫的错误概率为 47.4%。根据真实数据,变异测试的灵敏度、特异性和相关性估计分别约为 98.98%、99.996% 和 93%,阳性一致调用的错误率约为 2.5%。在协变量效应分析中,尽管协变量解释的偏差部分在不一致模型和误差模型中有所不同,但不一致模型和误差模型的效应函数形式接近:结论:在两个测序结果条件独立的情况下,一致-不一致标准似乎可以作为替代标准。结论:在两个测序结果具有条件独立性的情况下,一致-不一致标准作为替代标准似乎是可以接受的。然而,在相关性较高的情况下,该标准就会受到质疑,因为在一致的结果中会出现很高比例的错误一致结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Human Heredity
Human Heredity 生物-遗传学
CiteScore
2.50
自引率
0.00%
发文量
12
审稿时长
>12 weeks
期刊介绍: Gathering original research reports and short communications from all over the world, ''Human Heredity'' is devoted to methodological and applied research on the genetics of human populations, association and linkage analysis, genetic mechanisms of disease, and new methods for statistical genetics, for example, analysis of rare variants and results from next generation sequencing. The value of this information to many branches of medicine is shown by the number of citations the journal receives in fields ranging from immunology and hematology to epidemiology and public health planning, and the fact that at least 50% of all ''Human Heredity'' papers are still cited more than 8 years after publication (according to ISI Journal Citation Reports). Special issues on methodological topics (such as ‘Consanguinity and Genomics’ in 2014; ‘Analyzing Rare Variants in Complex Diseases’ in 2012) or reviews of advances in particular fields (‘Genetic Diversity in European Populations: Evolutionary Evidence and Medical Implications’ in 2014; ‘Genes and the Environment in Obesity’ in 2013) are published every year. Renowned experts in the field are invited to contribute to these special issues.
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