Bosworth Colleen M, Grandhi Sneha, Gould Meetha P, LaFramboise Thomas
Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
BMC Bioinformatics. 2017 Oct 16;18(Suppl 12):407. doi: 10.1186/s12859-017-1821-7.
Chromosomal deletions represent an important class of human genetic variation. Various methods have been developed to mine "next-generation" sequencing (NGS) data to detect deletions and quantify their clonal abundances. These methods have focused almost exclusively on the nuclear genome, ignoring the mitochondrial chromosome (mtDNA). Detecting mtDNA deletions requires special care. First, the chromosome's relatively small size (16,569 bp) necessitates the ability to detect extremely focal events. Second, the chromosome can be present at thousands of copies in a single cell (in contrast to two copies of nuclear chromosomes), and mtDNA deletions may be present on only a very small percentage of chromosomes. Here we present a method, termed MitoDel, to detect mtDNA deletions from NGS data.
We validate the method on simulated and real data, and show that MitoDel can detect novel and previously-reported mtDNA deletions. We establish that MitoDel can find deletions such as the "common deletion" at heteroplasmy levels well below 1%.
MitoDel is a tool for detecting large mitochondrial deletions at low heteroplasmy levels. The tool can be downloaded at http://mendel.gene.cwru.edu/laframboiselab/ .
染色体缺失是人类遗传变异的重要类别。已开发出各种方法来挖掘“下一代”测序（NGS）数据，以检测缺失并量化其克隆丰度。这些方法几乎完全集中于核基因组，而忽略了线粒体染色体（mtDNA）。检测mtDNA缺失需要特别注意。首先，该染色体相对较小（16,569 bp），这就需要具备检测极其局部事件的能力。其次，该染色体在单个细胞中可能存在数千个拷贝（与核染色体的两个拷贝形成对比），并且mtDNA缺失可能仅存在于极小比例的染色体上。在此，我们提出一种名为MitoDel的方法，用于从NGS数据中检测mtDNA缺失。
我们在模拟数据和真实数据上验证了该方法，并表明MitoDel能够检测到新的以及先前报道过的mtDNA缺失。我们确定MitoDel能够在异质性水平远低于1%的情况下发现诸如“常见缺失”之类的缺失。
MitoDel是一种用于在低异质性水平下检测大型线粒体缺失的工具。该工具可从http://mendel.gene.cwru.edu/laframboiselab/ 下载。
