LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets.
LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets.
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DOI：
10.1093/nar/gks918
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发表时间：
2012-12
影响因子：
14.9
通讯作者：
Nagarajan N
中科院分区：
文献类型：
--
作者：
Wilm A;Aw PP;Bertrand D;Yeo GH;Ong SH;Wong CH;Khor CC;Petric R;Hibberd ML;Nagarajan N
从病毒到细菌分离株再到肿瘤样品，一系列生物系统中细胞群体异质性的研究已经被测序通量的最新进展所改变。虽然所提供的高覆盖率原则上可用于鉴定群体中非常罕见的变异，但现有的特设方法通常无法区分真正的变异与测序错误。我们报告了一种方法（LoFreq），该方法对测序运行特异性错误率进行建模，以准确地调用<0.05%的群体中发生的变异。使用模拟和真实的数据集（病毒，细菌和人类），我们表明LoFreq具有近乎完美的特异性，与现有方法相比具有显着提高的灵敏度，并且可以有效地分析深度Illumina测序数据集，而无需诉诸近似或解析。我们还在两个不同的平台（Fluidigm和Sequenom）上对LoFreq进行了实验验证，并将其应用于从胃癌外显子组测序数据集中调用罕见的体细胞变异。LoFreq的源代码和可执行文件可在http://sourceforge.net/projects/lofreq/上免费获得。
The study of cell-population heterogeneity in a range of biological systems, from viruses to bacterial isolates to tumor samples, has been transformed by recent advances in sequencing throughput. While the high-coverage afforded can be used, in principle, to identify very rare variants in a population, existing ad hoc approaches frequently fail to distinguish true variants from sequencing errors. We report a method (LoFreq) that models sequencing run-specific error rates to accurately call variants occurring in <0.05% of a population. Using simulated and real datasets (viral, bacterial and human), we show that LoFreq has near-perfect specificity, with significantly improved sensitivity compared with existing methods and can efficiently analyze deep Illumina sequencing datasets without resorting to approximations or heuristics. We also present experimental validation for LoFreq on two different platforms (Fluidigm and Sequenom) and its application to call rare somatic variants from exome sequencing datasets for gastric cancer. Source code and executables for LoFreq are freely available at http://sourceforge.net/projects/lofreq/.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1158/1940-6207.capr-10-0326
发表时间：
2011-05
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Chatterjee A;Dasgupta S;Sidransky D
通讯作者：
Sidransky D
影响因子：
10.5
作者：
Inda, Maria-del-Mar;Bonavia, Rudy;Furnari, Frank
通讯作者：
Furnari, Frank
影响因子：
9.8
作者：
Kloss-Brandstaetter, Anita;Schaefer, Georg;Kronenberg, Florian
通讯作者：
Kronenberg, Florian
影响因子：
12.3
作者：
Harismendy O;Schwab RB;Bao L;Olson J;Rozenzhak S;Kotsopoulos SK;Pond S;Crain B;Chee MS;Messer K;Link DR;Frazer KA
通讯作者：
Frazer KA