The effect of strand bias in Illumina short-read sequencing data.
The effect of strand bias in Illumina short-read sequencing data.
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DOI：
10.1186/1471-2164-13-666
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发表时间：
2012-11-24
期刊：
影响因子：
4.4
通讯作者：
Shyr Y
中科院分区：
文献类型：
--
作者：
Guo Y;Li J;Li CI;Long J;Samuels DC;Shyr Y
当使用Illumina高通量短读段数据时，有时从正链和负链推断的基因型显著不同，其中一个是纯合的，另一个是杂合的。这种现象被称为链偏差。在这项研究中，我们使用Illumina短读测序数据来评估链偏倚对基因分型质量的影响，并探讨链偏倚的可能原因。我们收集了来自22名患者的22份乳腺癌样本，并使用Illumina GAIIx机器对其外显子组进行测序。通过比较从该测序数据推断的基因型与从SNP芯片数据推断的基因型之间的一致性，我们发现，当使用测序数据时，与具有低或无链偏倚的SNP相比，具有极端链偏倚的SNP并不具有显著较低的一致率。然而，该结果可能受到外显子组测序和SNP芯片数据中存在的SNP的小子集的限制。我们进一步比较了具有低或无链偏好的SNP与具有极端链偏好的SNP之间的转换和颠换比率以及新的非同义SNP的数量，发现具有低或无链偏好的SNP具有更好的整体质量。我们还发现，在这些样品中，链偏倚随机发生在基因组位置，并且在样品中没有观察到一致的链偏倚位置模式。通过比较来自两个不同比对器BWA和Bowtie的结果，我们发现非常一致的链偏好模式。因此，链偏差不太可能由比对伪影引起。我们成功地复制了我们的结果，使用两个额外的独立数据集，不同的捕获方法和Illumina测序仪。极端的链偏倚表明SNP的潜在高假阳性率。
When using Illumina high throughput short read data, sometimes the genotype inferred from the positive strand and negative strand are significantly different, with one homozygous and the other heterozygous. This phenomenon is known as strand bias. In this study, we used Illumina short-read sequencing data to evaluate the effect of strand bias on genotyping quality, and to explore the possible causes of strand bias. We collected 22 breast cancer samples from 22 patients and sequenced their exome using the Illumina GAIIx machine. By comparing the consistency between the genotypes inferred from this sequencing data with the genotypes inferred from SNP chip data, we found that, when using sequencing data, SNPs with extreme strand bias did not have significantly lower consistency rates compared to SNPs with low or no strand bias. However, this result may be limited by the small subset of SNPs present in both the exome sequencing and the SNP chip data. We further compared the transition and transversion ratio and the number of novel non-synonymous SNPs between the SNPs with low or no strand bias and those with extreme strand bias, and found that SNPs with low or no strand bias have better overall quality. We also discovered that the strand bias occurs randomly at genomic positions across these samples, and observed no consistent pattern of strand bias location across samples. By comparing results from two different aligners, BWA and Bowtie, we found very consistent strand bias patterns. Thus strand bias is unlikely to be caused by alignment artifacts. We successfully replicated our results using two additional independent datasets with different capturing methods and Illumina sequencers. Extreme strand bias indicates a potential high false-positive rate for SNPs.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
30.8
作者：
Zheng, Wei;Long, Jirong;Gao, Yu-Tang;Li, Chun;Zheng, Ying;Xiang, Yong-Bin;Wen, Wanqing;Levy, Shawn;Deming, Sandra L.;Haines, Jonathan L.;Gu, Kai;Fair, Alecia Malin;Cai, Qiuyin;Lu, Wei;Shu, Xiao-Ou
通讯作者：
Shu, Xiao-Ou
影响因子：
3.9
作者：
Yang, ZH;Nielsen, R
通讯作者：
Nielsen, R
影响因子：
14.9
作者：
Cock PJ;Fields CJ;Goto N;Heuer ML;Rice PM
通讯作者：
Rice PM
影响因子：
64.8
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Altshuler, David;Durbin, Richard M.;Abecasis, Goncalo R.;Bentley, David R.;Chakravarti, Aravinda;Clark, Andrew G.;Collins, Francis S.;De la Vega, Francisco M.;Donnelly, Peter;Egholm, Michael;Flicek, Paul;Gabriel, Stacey B.;Gibbs, Richard A.;Knoppers, Bartha M.;Lander, Eric S.;Lehrach, Hans;Mardis, Elaine R.;McVean, Gil A.;Nickerson, DebbieA.;Peltonen, Leena;Schafer, Alan J.;Sherry, Stephen T.;Wang, Jun;Wilson, Richard K.;Gibbs, Richard A.;Deiros, David;Metzker, Mike;Muzny, Donna;Reid, Jeff;Wheeler, David;Wang, Jun;Li, Jingxiang;Jian, Min;Li, Guoqing;Li, Ruiqiang;Liang, Huiqing;Tian, Geng;Wang, Bo;Wang, Jian;Wang, Wei;Yang, Huanming;Zhang, Xiuqing;Zheng, Huisong;Lander, Eric S.;Altshuler, David L.;Ambrogio, Lauren;Bloom, Toby;Cibulskis, Kristian;Fennell, Tim J.;Gabriel, Stacey B.;Jaffe, David B.;Shefler, Erica;Sougnez, Carrie L.;Bentley, David R.;Gormley, Niall;Humphray, Sean;Kingsbury, Zoya;Koko-Gonzales, Paula;Stone, Jennifer;McKernan, Kevin J.;Costa, Gina L.;Ichikawa, Jeffry K.;Lee, Clarence C.;Sudbrak, Ralf;Lehrach, Hans;Borodina, Tatiana A.;Dahl, Andreas;Davydov, Alexey N.;Marquardt, Peter;Mertes, Florian;Nietfeld, Wilfiried;Rosenstiel, Philip;Schreiber, Stefan;Soldatov, Aleksey V.;Timmermann, Bernd;Tolzmann, Marius;Egholm, Michael;Affourtit, Jason;Ashworth, Dana;Attiya, Said;Bachorski, Melissa;Buglione, Eli;Burke, Adam;Caprio, Amanda;Celone, Christopher;Clark, Shauna;Conners, David;Desany, Brian;Gu, Lisa;Guccione, Lorri;Kao, Kalvin;Kebbel, Andrew;Knowlton, Jennifer;Labrecque, Matthew;McDade, Louise;Mealmaker, Craig;Minderman, Melissa;Nawrocki, Anne;Niazi, Faheem;Pareja, Kristen;Ramenani, Ravi;Riches, David;Song, Wanmin;Turcotte, Cynthia;Wang, Shally;Mardis, Elaine R.;Dooling, David;Fulton, Lucinda;Fulton, Robert;Weinstock, George;Durbin, Richard M.;Burton, John;Carter, David M.;Churcher, Carol;Coffey, Alison;Cox, Anthony;Palotie, Aarno;Quail, Michael;Skelly, Tom;Stalker, James;Swerdlow, Harold P.;Turner, Daniel;De Witte, Anniek;Giles, Shane;Gibbs, Richard A.;Wheeler, David;Bainbridge, Matthew;Challis, Danny;Sabo, Aniko;Yu, Fuli;Yu, Jin;Wang, Jun;Fang, Xiaodong;Guo, Xiaosen;Li, Ruiqiang;Li, Yingrui;Luo, Ruibang;Tai, Shuaishuai;Wu, Honglong;Zheng, Hancheng;Zheng, Xiaole;Zhou, Yan;Yang, Huanming;Marth, Gabor T.;Garrison, Erik P.;Huang, Weichun;Indap, Amit;Kural, Deniz;Lee, Wan-Ping;Leong, Wen Fung;Huang, Weichun;Indap, Amit;Kural, Deniz;Lee, Wan-Ping;Leong, Wen Fung;Quinlan, Aaron R.;Stewart, Chip;Stromberg, Michael P.;Ward, Alistair N.;Wu, Jiantao;Lee, Charles;Mills, Ryan E.;Shi, Xinghua;Daly, Mark J.;DePristo, Mark A.;Altshuler, David L.;Ball, Aaron D.;Banks, Eric;Bloom, Toby;Browning, Brian L.;Cibulskis, Kristian;Fennell, Tim J.;Garimella, Kiran V.;Grossman, Sharon R.;Handsaker, Robert E.;Hanna, Matt;Hartl, Chris;Jaffe, David B.;Kernytsky, Andrew M.;Korn, Joshua M.;Li, Heng;Maguire, Jared R.;McCarroll, Steven A.;McKenna, Aaron;Nemesh, James C.;Philippakis, Anthony A.;Poplin, Ryan E.;Price, Alkes;Rivas, Manuel A.;Sabeti, Pardis C.;Schaffner, Stephen F.;Shefler, Erica;Shlyakhter, Ilya A.;Cooper, David N.;Ball, Edward V.;Mort, Matthew;Phillips, Andrew D.;Stenson, Peter D.;Sebat, Jonathan;Makarov, Vladimir;Ye, Kenny;Yoon, Seungtai C.;Bustamante, Carlos D.;Clark, Andrew G.;Boyko, Adam;Degenhardt, Jeremiah;Gravel, Simon;Gutenkunst, Ryan N.;Kaganovich, Mark;Keinan, Alon;Lacroute, Phil;Ma, Xia;Reynolds, Andy;Clarke, Laura;Flicek, Paul;Cunningham, Fiona;Herrero, Javier;Keenen, Stephen;Kulesha, Eugene;Leinonen, Rasko;McLaren, WilliamM.;Radhakrishnan, Rajesh;Smith, Richard E.;Zalunin, Vadim;Zheng-Bradley, Xiangqun;Korbel, Jan O.;Stuetz, Adrian M.;Humphray, Sean;Bauer, Markus;Cheetham, R. Keira;Cox, Tony;Eberle, Michael;James, Terena;Kahn, Scott;Murray, Lisa;Ye, Kai;De La Vega, Francisco M.;Fu, Yutao;Hyland, Fiona C. 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通讯作者：
McVean, Gil A.