PolyScan: An automatic indel and SNP detection approach to the analysis of human resequencing data
PolyScan: An automatic indel and SNP detection approach to the analysis of human resequencing data
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DOI：
10.1101/gr.6151507
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发表时间：
2007-05-01
期刊：
影响因子：
7
通讯作者：
Mardis, Elaine R.
中科院分区：
文献类型：
--
作者：
Chen, Ken;McLellan, Michael D.;Mardis, Elaine R.
小插入和缺失（indels）和单核苷酸多态性（SNP）是被认为与多种人类疾病相关的常见遗传变异。由于基因组的大小和复杂性，手动表征个体中的这些变异中的每一个是不切实际的。虽然在从二倍体PCR产物的序列中自动化单碱基突变发现方面已经取得了重大进展，但是自动化和可靠的indel检测仍然构成困难的挑战。在本文中，我们提出了PolyScan，一种算法和软件实现，旨在提供从头杂合indel检测和改进的SNP识别的背景下，高通量医学重测序。对人类二倍体基于PCR的序列数据集（由来自13个基因的90，270个迹线组成）的测试表明，PolyScan识别出与151个共有indel位点中的90%相似，并且与先前通过手动检查识别出的1546个杂合indel中的84%相似。对肿瘤来源数据的测试表明，与其他突变检测软件相比，PolyScan能更好地识别高质量、低水平的突变。此外，SNP鉴定在重新处理其他程序的结果时得到改善。这些结果表明PolyScan可能在后人类基因组计划研究时代发挥有用的作用。
Small insertions and deletions (indels) and single nucleotide polymorphisms (SNPs) are common genetic variants that are thought to be associated with a wide variety of human diseases. Owing to the genome's size and complexity, manually characterizing each one of these variations in an individual is not practical. While significant progress has been made in automated single-base mutation discovery from the sequences of diploid PCR products, automated and reliable detection of indels continues to pose difficult challenges. In this paper, we present PolyScan, an algorithm and software implementation designed to provide de novo heterozygous indel detection and improved SNP identification in the context of high-throughput medical resequencing. Tests on a human diploid PCR-based sequence data set, consisting of 90,270 traces from 13 genes, indicate that PolyScan identified similar to 90% of the 151 consensus indel sites and similar to 84% of the 1546 heterozygous indels previously identified by manual inspection. Tests on tumor-derived data show that PolyScan better identifies high-quality, low-level mutations as compared with other mutation detection software. Moreover, SNP identification improves when reprocessing the results of other programs. These results suggest that PolyScan may play a useful role in the post human genome project research era.