SNPdetector: A software tool for sensitive and accurate SNP detection
SNPdetector: A software tool for sensitive and accurate SNP detection
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DOI：
10.1371/journal.pcbi.0010053
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发表时间：
2005-10-01
影响因子：
4.3
通讯作者：
Buetow, KH
中科院分区：
文献类型：
--
作者：
Zhang, JH;Wheeler, DA;Buetow, KH
单核苷酸多态性 (SNP) 和突变的鉴定对于发现复杂疾病的遗传易感性非常重要。 PCR 重测序是从头发现 SNP 的首选方法。然而，推定 SNP 的手动管理一直是该方法应用于高通量筛选的主要瓶颈。因此，开发一种更灵敏、更准确的自动 SNP 检测计算方法至关重要。我们开发了一款软件工具 SNP detector，用于自动识别基于荧光的重测序读数中的 SNP 和突变。 SNPDetector 旨在模拟人类视觉检查的过程，具有非常低的误报率和漏报率。我们通过将其结果与人类检查、PolyPhred（一种流行的 SNP 检测工具）和三项大规模研究中的独立基因型测定得出的结果进行比较，证明了 SNP detector 在 SNP 和突变分析方面的卓越性能。第一项研究鉴定并验证了属于小家鼠 (Mus musculus) 或鲫鱼 (M. spretus) 的 25 个近交系小鼠品系的 4,650 个痕迹中的亚种间和亚种内变异。在 1,167 个小鼠 SNP 中的两个中观察到 CAST/Ei 品系中意外的杂合性。第二项研究在人类基因组的五个 ENCODE 区域中确定了 11,241 个候选 SNP，覆盖了 2.5 Mb 的基因组序列。大约50%的候选SNP被选择用于实验基因分型；验证率超过95%。第三项研究在 1,236 条斑马鱼的 64,896 个痕迹中检测到 ENU 诱导的突变（等位基因频率为 0.04%）。我们对三个大型且多样化的测试数据集的分析表明，SNP detector 是基因组规模研究和大样本临床研究的有效工具。 SNPDetector 运行在 Unix/Linux 平台上，并且可公开使用 (http://Ipg.nci.nih.gov)。
Identification of single nucleotide polymorphisms (SNPs) and mutations is important for the discovery of genetic predisposition to complex diseases. PCR resequencing is the method of choice for de novo SNP discovery. However, manual curation of putative SNPs has been a major bottleneck in the application of this method to high-throughput screening. Therefore it is critical to develop a more sensitive and accurate computational method for automated SNP detection. We developed a software tool, SNPdetector, for automated identification of SNPs and mutations in fluorescence-based resequencing reads. SNPdetector was designed to model the process of human visual inspection and has a very low false positive and false negative rate. We demonstrate the superior performance of SNPdetector in SNP and mutation analysis by comparing its results with those derived by human inspection, PolyPhred (a popular SNP detection tool), and independent genotype assays in three large-scale investigations. The first study identified and validated inter- and intra-subspecies variations in 4,650 traces of 25 inbred mouse strains that belong to either the Mus musculus species or the M. spretus species. Unexpected heterozgyosity in CAST/Ei strain was observed in two out of 1,167 mouse SNPs. The second study identified 11,241 candidate SNPs in five ENCODE regions of the human genome covering 2.5 Mb of genomic sequence. Approximately 50% of the candidate SNPs were selected for experimental genotyping; the validation rate exceeded 95%. The third study detected ENU-induced mutations (at 0.04% allele frequency) in 64,896 traces of 1,236 zebra fish. Our analysis of three large and diverse test datasets demonstrated that SNPdetector is an effective tool for genome-scale research and for large-sample clinical studies. SNPdetector runs on Unix/Linux platform and is available publicly (http://Ipg.nci.nih.gov).