Pre-capture multiplexing provides additional power to detect copy number variation in exome sequencing.
Pre-capture multiplexing provides additional power to detect copy number variation in exome sequencing.
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DOI：
10.1186/s12859-021-04246-w
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发表时间：
2021-07-20
影响因子：
3
通讯作者：
Wilhelmsen KC
中科院分区：
文献类型：
--
作者：
Filer DL;Kuo F;Brandt AT;Tilley CR;Mieczkowski PA;Berg JS;Robasky K;Li Y;Bizon C;Tilson JL;Powell BC;Bost DM;Jeffries CD;Wilhelmsen KC
随着外显子组测序（ES）融入临床实践，我们应该尽一切努力利用所产生的所有信息。拷贝数变异可能导致孟德尔疾病，但小拷贝数变异 (CNV) 常常因数据收集不足而被忽视或掩盖。许多小组已经开发出从 ES 中检测 CNV 的方法，但现有方法通常对于小型 CNV 表现不佳，并且依赖于临床实验室并不总是可用的大量样本。此外，方法通常依赖于贝叶斯方法，在先验知识不足的情况下需要用户定义的先验。该报告首先展示了多重外显子组捕获（捕获前汇集样本）的好处，然后提出了一种围绕多重捕获构建的新型检测算法 mcCNV（“多重捕获 CNV”）。我们证明：（1）多重捕获减少了样本间方差； (2) 我们的 mcCNV 方法是一种基于深度的新型算法，用于从多重捕获 ES 数据中检测 CNV，改进了小 CNV 的检测。我们将我们的新颖方法（与先验信息无关）与常用的外显子组深度进行了对比。在一项模拟研究中，mcCNV 表现出了良好的错误发现率 (FDR)。与匹配基因组测序的调用相比，我们发现 mcCNV 算法的性能与 ExomeDepth 相当。实施多重捕获可提高检测单外显子 CNV 的能力。新颖的 mcCNV 算法可能提供比 ExomeDepth 更有利的 FDR。我们的方法的最大好处来自于（1）不需要参考样本数据库，（2）不需要有关变异的普遍性或大小的先验信息。在线版本包含可在 10.1186/s12859-021-04246-w 获取的补充材料。
As exome sequencing (ES) integrates into clinical practice, we should make every effort to utilize all information generated. Copy-number variation can lead to Mendelian disorders, but small copy-number variants (CNVs) often get overlooked or obscured by under-powered data collection. Many groups have developed methodology for detecting CNVs from ES, but existing methods often perform poorly for small CNVs and rely on large numbers of samples not always available to clinical laboratories. Furthermore, methods often rely on Bayesian approaches requiring user-defined priors in the setting of insufficient prior knowledge. This report first demonstrates the benefit of multiplexed exome capture (pooling samples prior to capture), then presents a novel detection algorithm, mcCNV (“multiplexed capture CNV”), built around multiplexed capture. We demonstrate: (1) multiplexed capture reduces inter-sample variance; (2) our mcCNV method, a novel depth-based algorithm for detecting CNVs from multiplexed capture ES data, improves the detection of small CNVs. We contrast our novel approach, agnostic to prior information, with the the commonly-used ExomeDepth. In a simulation study mcCNV demonstrated a favorable false discovery rate (FDR). When compared to calls made from matched genome sequencing, we find the mcCNV algorithm performs comparably to ExomeDepth. Implementing multiplexed capture increases power to detect single-exon CNVs. The novel mcCNV algorithm may provide a more favorable FDR than ExomeDepth. The greatest benefits of our approach derive from (1) not requiring a database of reference samples and (2) not requiring prior information about the prevalance or size of variants. The online version contains supplementary material available at 10.1186/s12859-021-04246-w.
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DOI：
10.1093/bioinformatics/bts526
发表时间：
2012-11-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
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作者：
Plagnol V;Curtis J;Epstein M;Mok KY;Stebbings E;Grigoriadou S;Wood NW;Hambleton S;Burns SO;Thrasher AJ;Kumararatne D;Doffinger R;Nejentsev S
通讯作者：
Nejentsev S
DOI：
10.1093/bioinformatics/btr670
发表时间：
2012-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Boeva V;Popova T;Bleakley K;Chiche P;Cappo J;Schleiermacher G;Janoueix-Lerosey I;Delattre O;Barillot E
通讯作者：
Barillot E
影响因子：
9.8
作者：
Fromer, Menachem;Moran, Jennifer L.;Purcell, Shaun M.
通讯作者：
Purcell, Shaun M.
影响因子：
3.7
作者：
Neiman, Marten;Sundling, Simon;Klevebring, Daniel
通讯作者：
Klevebring, Daniel
DOI：
10.1016/0005-2795(75)90109-9
发表时间：
1975-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
MATTHEWS, BW
通讯作者：
MATTHEWS, BW