Screening the human exome: a comparison of whole genome and whole transcriptome sequencing.
Screening the human exome: a comparison of whole genome and whole transcriptome sequencing.
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DOI：
10.1186/gb-2010-11-5-r57
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发表时间：
2010
期刊：
影响因子：
12.3
通讯作者：
Center for HIV/AIDS Vaccine Immunology (CHAVI)
中科院分区：
文献类型：
--
作者：
Cirulli ET;Singh A;Shianna KV;Ge D;Smith JP;Maia JM;Heinzen EL;Goedert JJ;Goldstein DB;Center for HIV/AIDS Vaccine Immunology (CHAVI)
对于有效识别大型人类样本集中的所有编码变体的方法的开发，人们非常感兴趣。有三种方法：全基因组测序，使用外显子捕获方法和RNA-seq进行全基因测序。尽管全基因组测序最完整，但成本效益的替代方案仍然很重要。
在这里，我们通过将通过高覆盖范围的全基因组测序与通过同一个体中高覆盖RNA-Seq识别的变体进行比较，对RNA-Seq如何识别人类编码变体的良好识别。这种比较使我们能够直接评估RNA-seq在识别编码变体中的敏感性和特异性，并评估关键参数（例如覆盖率和基因表达水平）如何相互作用以影响性能。我们发现，尽管使用RNA-Seq捕获了整个基因组测序鉴定的外显子变体中的40％。当专注于已知在源组织中良好表达的基因时，该数字上升到81％。我们还发现，在使用RNA-Seq数据时，尤其是在较高水平的覆盖范围时，高误报率可能会出现问题。
我们得出的结论是，只要可以使用与所研究性状相关的组织并实施了合适的质量控制筛选，RNA-Seq就是一种快速且廉价的替代方法，可以在具有足够高表达水平的基因中找到编码变体。
There is considerable interest in the development of methods to efficiently identify all coding variants present in large sample sets of humans. There are three approaches possible: whole-genome sequencing, whole-exome sequencing using exon capture methods, and RNA-Seq. While whole-genome sequencing is the most complete, it remains sufficiently expensive that cost effective alternatives are important. Here we provide a systematic exploration of how well RNA-Seq can identify human coding variants by comparing variants identified through high coverage whole-genome sequencing to those identified by high coverage RNA-Seq in the same individual. This comparison allowed us to directly evaluate the sensitivity and specificity of RNA-Seq in identifying coding variants, and to evaluate how key parameters such as the degree of coverage and the expression levels of genes interact to influence performance. We find that although only 40% of exonic variants identified by whole genome sequencing were captured using RNA-Seq; this number rose to 81% when concentrating on genes known to be well-expressed in the source tissue. We also find that a high false positive rate can be problematic when working with RNA-Seq data, especially at higher levels of coverage. We conclude that as long as a tissue relevant to the trait under study is available and suitable quality control screens are implemented, RNA-Seq is a fast and inexpensive alternative approach for finding coding variants in genes with sufficiently high expression levels.
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剪接的组织特异性遗传控制：对复杂性状的研究的影响。
影响因子：
9.8
作者：
Heinzen EL;Ge D;Cronin KD;Maia JM;Shianna KV;Gabriel WN;Welsh-Bohmer KA;Hulette CM;Denny TN;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Shah, Sohrab P.;Morin, Ryan D.;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
12.3
作者：
Clark TA;Schweitzer AC;Chen TX;Staples MK;Lu G;Wang H;Williams A;Blume JE
通讯作者：
Blume JE
DOI：
10.1093/bioinformatics/btp352
发表时间：
2009-08-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Li H;Handsaker B;Wysoker A;Fennell T;Ruan J;Homer N;Marth G;Abecasis G;Durbin R;1000 Genome Project Data Processing Subgroup
通讯作者：
1000 Genome Project Data Processing Subgroup