Methods for detecting short indels from high-throughput sequence data

描述(由申请人提供)： 近年来，高通量测序技术改变了我们对人类遗传变异的理解，使人类个体基因组测序以及种群规模的测序成为可能。短插入/短缺失(INDELs)是人类基因组中第二种最常见的变异形式，这在功能上也很重要。INDELs没有受到单核苷酸变体(SNV)和结构变体那么多的关注，部分原因是从高通量序列数据集中检测INDELs具有挑战性，而且与识别单核苷酸变体的方法相比，现有的计算方法显示出明显较低的灵敏度和特异度。因此，迫切需要新的计算方法来应对INDELs的检测和基因分型带来的挑战。我们建议开发新的方法从个体和群体规模的序列数据集中检测短Indel，该方法将利用特定于序列上下文的Indel错误率信息以及来自大规模序列数据集的测序平台来生成准确的Indel调用和基因类型。这些方法的发展将显著提高研究人员从测序数据集中提取关于遗传变异的准确信息的能力，提高他们识别与疾病易感性相关的变异的能力，并改善我们对人类基因组中短INDELs的范围和分布的理解。

DESCRIPTION (provided by applicant): In recent years, high-throughput sequencing technologies have transformed our understanding of human genetic variation by enabling the sequencing of individual human genomes as well as sequencing on a population-scale. Short insertions/deletions (indels) represent the second most frequent form of variation in the human genome, which is also functionally important. Indels have not received as much attention as single nucleotide variants (SNVs) and structural variants in part because the detection of indels from high-throughput sequence datasets is challenging and available computational methods exhibit significantly lower sensitivity and specificity compared to methods that are designed to identify single nucleotide variants. Novel computational methods that address the challenge presented by the detection and genotyping of indels are thus urgently needed. We propose to develop novel methods for the detection of short indels from both individual and population-scale sequence datasets that will utilize information about indel error rates that are specific to sequence context as well as sequencing platform from large-scale sequence datasets in order to generate accurate indel calls and genotypes. The development of these methods will significantly enhance the ability of researchers to extract accurate information about genetic variation from sequencing datasets, improve their ability to identify variants that are associated with disease susceptibility and improve our understanding of the extent and distribution of short indels in the human genome.