HDR-del: A tool based on Hamming distance for prioritizing pathogenic chromosomal deletions in exome sequencing
HDR-del: A tool based on Hamming distance for prioritizing pathogenic chromosomal deletions in exome sequencing
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DOI：
10.1002/humu.23298
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发表时间：
2017-12-01
期刊：
影响因子：
3.9
通讯作者：
Ott, Jurg
中科院分区：
文献类型：
--
作者：
Imai-Okazaki, Atsuko;Kohda, Masakazu;Ott, Jurg
高密度寡核苷酸芯片已被广泛用于检测致病性染色体缺失。除了高密度寡核苷酸阵列，使用全外显子组测序的程序已可用于使用覆盖深度估计拷贝数变异。在这里，我们提出了一种新的统计方法，HDR-del，优先致病性染色体缺失的基础上汉明距离外显子组测序。在由外显子组测序生成的vcf（变体调用格式）文件中，半合子染色体缺失区域缺乏杂合变体，并导致明显的长纯合性（ROH）。在我们的汉明距离比（HDR）-del方法中，我们使用HDR计算受影响个体和对照个体之间杂合状态的“差异”，该HDR在所有候选染色体缺失区域上定义为ROH长于1 Mbp。使用一个合适的测试统计量，这是一个真正的致病性缺失区域预计将是大的，我们优先考虑候选染色体缺失区域的基础上，这个统计量。在我们的方法中，我们能够大大缩小真正的致病性染色体缺失区域，这在四名线粒体疾病患者中得到了高密度寡核苷酸阵列的证实。我们的HDR-del方法是一种检测染色体缺失的简单方法。
High-density oligonucleotide arrays have widely been used to detect pathogenic chromosomal deletions. In addition to high-density oligonucleotide arrays, programs using whole-exome sequencing have become available for estimating copy-number variations using depth of coverage. Here, we propose a new statistical method, HDR-del, to prioritize pathogenic chromosomal deletions based on Hamming distance in exome sequencing. In vcf (variant call format) files generated from exome sequencing, hemizygous chromosomal deletion regions lack heterozygous variants and lead to apparent long runs of homozygosity (ROH). In our Hamming distance ratio (HDR)-del approach, we calculate the "difference" in heterozygous status between an affected individual and control individuals using the HDR over all candidate chromosomal deletion regions defined as ROH longer than 1Mbp. Using a suitable test statistic, which is expected to be large for a true pathogenic deletion region, we prioritize candidate chromosomal deletion regions based on this statistic. In our approach, we were able to considerably narrow down true pathogenic chromosomal deletion regions, which were confirmed by high-density oligonucleotide arrays in four mitochondrial disease patients. Our HDR-del approach represents an easy method for detecting chromosomal deletions.