Dierckxsens Nicolas, Mardulyn Patrick, Smits Guillaume
Interuniversity Institute of Bioinformatics in Brussels (IB2), Université Libre de Bruxelles and Vrije Universiteit Brussel, Triomflaan CP 263, 1050 Brussels, Belgium.
Evolutionary Biology and Ecology, CP 160/12, Université Libre de Bruxelles, Av. F. D. Roosevelt 50, B-1050 Brussels, Belgium.
NAR Genom Bioinform. 2019 Oct 24;2(1):lqz011. doi: 10.1093/nargab/lqz011. eCollection 2020 Mar.
Heteroplasmy, the existence of multiple mitochondrial haplotypes within an individual, has been studied across different scientific fields. Mitochondrial genome polymorphisms have been linked to multiple severe disorders and are of interest to evolutionary studies and forensic science. Before the development of massive parallel sequencing (MPS), most studies of mitochondrial genome variation were limited to short fragments and to heteroplasmic variants associated with a relatively high frequency (>10%). By utilizing ultra-deep sequencing, it has now become possible to uncover previously undiscovered patterns of intra-individual polymorphisms. Despite these technological advances, it is still challenging to determine the origin of the observed intra-individual polymorphisms. We therefore developed a new method that not only detects intra-individual polymorphisms within mitochondrial and chloroplast genomes more accurately, but also looks for linkage among polymorphic sites by assembling the sequence around each detected polymorphic site. Our benchmark study shows that this method is capable of detecting heteroplasmy more accurately than any method previously available and is the first tool that is able to completely or partially reconstruct the sequence for each mitochondrial haplotype (allele). The method is implemented in our open source software NOVOPlasty that can be downloaded at https://github.com/ndierckx/NOVOPlasty.
异质性是指个体内存在多种线粒体单倍型，这一现象已在不同科学领域得到研究。线粒体基因组多态性与多种严重疾病有关，并且受到进化研究和法医学的关注。在大规模平行测序（MPS）技术发展之前，大多数线粒体基因组变异研究仅限于短片段以及与相对高频（>10%）相关的异质变体。通过利用超深度测序，现在已经能够发现以前未被发现的个体内多态性模式。尽管有这些技术进步，但确定观察到的个体内多态性的起源仍然具有挑战性。因此，我们开发了一种新方法，该方法不仅能更准确地检测线粒体和叶绿体基因组内的个体内多态性，还能通过组装每个检测到的多态性位点周围的序列来寻找多态性位点之间的连锁关系。我们的基准研究表明，该方法比以前任何可用方法都能更准确地检测异质性，并且是第一个能够完全或部分重建每个线粒体单倍型（等位基因）序列的工具。该方法已在我们的开源软件NOVOPlasty中实现，可从https://github.com/ndierckx/NOVOPlasty下载。
