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标题：Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants
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作者：Aziz Belkadi ; Alexandre Bolze ; Yuval Itan 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：17
页码：5473-5478
DOI：10.1073/pnas.1418631112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceWhole-exome sequencing (WES) is gradually being optimized to identify mutations in increasing proportions of the protein-coding exome, but whole-genome sequencing (WGS) is becoming an attractive alternative. WGS is currently more expensive than WES, but its cost should decrease more rapidly than that of WES. We compared WES and WGS on six unrelated individuals. The distribution of quality parameters for single-nucleotide variants (SNVs) and insertions/deletions (indels) was more uniform for WGS than for WES. The vast majority of SNVs and indels were identified by both techniques, but an estimated 650 high-quality coding SNVs ([~]3% of coding variants) were detected by WGS and missed by WES. WGS is therefore slightly more efficient than WES for detecting mutations in the targeted exome. We compared whole-exome sequencing (WES) and whole-genome sequencing (WGS) in six unrelated individuals. In the regions targeted by WES capture (81.5% of the consensus coding genome), the mean numbers of single-nucleotide variants (SNVs) and small insertions/deletions (indels) detected per sample were 84,192 and 13,325, respectively, for WES, and 84,968 and 12,702, respectively, for WGS. For both SNVs and indels, the distributions of coverage depth, genotype quality, and minor read ratio were more uniform for WGS than for WES. After filtering, a mean of 74,398 (95.3%) high-quality (HQ) SNVs and 9,033 (70.6%) HQ indels were called by both platforms. A mean of 105 coding HQ SNVs and 32 indels was identified exclusively by WES whereas 692 HQ SNVs and 105 indels were identified exclusively by WGS. We Sanger-sequenced a random selection of these exclusive variants. For SNVs, the proportion of false-positive variants was higher for WES (78%) than for WGS (17%). The estimated mean number of real coding SNVs (656 variants, [~]3% of all coding HQ SNVs) identified by WGS and missed by WES was greater than the number of SNVs identified by WES and missed by WGS (26 variants). For indels, the proportions of false-positive variants were similar for WES (44%) and WGS (46%). Finally, WES was not reliable for the detection of copy-number variations, almost all of which extended beyond the targeted regions. Although currently more expensive, WGS is more powerful than WES for detecting potential disease-causing mutations within WES regions, particularly those due to SNVs.
关键词：exome ; genome ; next-generation sequencing ; genetic variants ; Mendelian disorders