JAX-CNV: A Whole-genome Sequencing-based Algorithm for Copy Number Detection at Clinical Grade Level.
JAX-CNV: A Whole-genome Sequencing-based Algorithm for Copy Number Detection at Clinical Grade Level.
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DOI：
10.1016/j.gpb.2021.06.003
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发表时间：
2022-12
影响因子：
9.5
通讯作者：
Zhang, Chengsheng
中科院分区：
文献类型：
--
作者：
Lee, Wan-Ping;Zhu, Qihui;Yang, Xiaofei;Liu, Silvia;Cerveira, Eliza;Ryan, Mallory;Mil-Homens, Adam;Bellfy, Lauren;Ye, Kai;Lee, Charles;Zhang, Chengsheng
我们的目的是开发一种基于全基因组测序（WGS）的拷贝数变异（CNV）调用算法，以取代染色体微阵列分析（CMA）的临床诊断的潜力。因此，开发JAX-CNV用于从WGS数据检测CNV。在31个样本上以盲态方式评价了该CNV调用算法的性能，并与临床验证的CMA报告的这31个样本的112个CNV进行了比较。结果表明，JAX-CNV 100%回忆起这些CNV。此外，JAX-CNV平均每个个体识别出30个CNV，与临床验证的CMA相比，大约增加了7倍。24个随机选择的CNV的实验验证显示一个假阳性，即，错误发现率（FDR）为4.17%。对低覆盖率数据的稳健性测试显示，对于大于300 kb（美国病理学家学会当前的阈值）的CNV，在覆盖率低至10倍时，灵敏度为100%。对于大于50 kb的CNVs，覆盖率大于20×的灵敏度为100%，15×为97%，10×为95%。我们开发了一个基于WGS的CNV管道，包括这个新开发的CNV调用程序JAX-CNV，并发现它能够以100%的灵敏度检测CMA报告的CNV，FDR约为4%。我们建议在多机构研究中进一步检查JAX-CNV，以证明从CMA到WGS的一级基因检测的过渡是合理的。JAX-CNV可从https://github.com/TheJacksonLaboratory/JAX-CNV获得。
We aimed to develop a whole-genome sequencing (WGS)-based copy number variant (CNV) calling algorithm with the potential of replacing chromosomal microarray assay (CMA) for clinical diagnosis. JAX-CNV is thus developed for CNV detection from WGS data. The performance of this CNV calling algorithm was evaluated in a blinded manner on 31 samples and compared to the 112 CNVs reported by clinically validated CMAs for these 31 samples. The result showed that JAX-CNV recalled 100% of these CNVs. Besides, JAX-CNV identified an average of 30 CNVs per individual, respresenting an approximately seven-fold increase compared to calls of clinically validated CMAs. Experimental validation of 24 randomly selected CNVs showed one false positive, i.e., a false discovery rate (FDR) of 4.17%. A robustness test on lower-coverage data revealed a 100% sensitivity for CNVs larger than 300 kb (the current threshold for College of American Pathologists) down to 10× coverage. For CNVs larger than 50 kb, sensitivities were 100% for coverages deeper than 20×, 97% for 15×, and 95% for 10×. We developed a WGS-based CNV pipeline, including this newly developed CNV caller JAX-CNV, and found it capable of detecting CMA-reported CNVs at a sensitivity of 100% with about a FDR of 4%. We propose that JAX-CNV could be further examined in a multi-institutional study to justify the transition of first-tier genetic testing from CMAs to WGS. JAX-CNV is available at https://github.com/TheJacksonLaboratory/JAX-CNV.
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DOI：
10.1097/gim.0b013e3181f8baad
发表时间：
2010-11
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Manning M;Hudgins L;Professional Practice and Guidelines Committee
通讯作者：
Professional Practice and Guidelines Committee
影响因子：
3.7
作者：
Dharanipragada P;Vogeti S;Parekh N
通讯作者：
Parekh N
DOI：
10.1038/oby.2010.323
发表时间：
2011-06
期刊：
Obesity (Silver Spring, Md.)
影响因子：
--
作者：
Chen Y;Liu YJ;Pei YF;Yang TL;Deng FY;Liu XG;Li DY;Deng HW
通讯作者：
Deng HW
影响因子：
12.3
作者：
Becker, Timothy;Lee, Wan-Ping;Malhotra, Ankit
通讯作者：
Malhotra, Ankit
影响因子：
56.9
作者：
Bailey, JA;Gu, ZP;Eichler, EE
通讯作者：
Eichler, EE