Smieszek Sandra, Mitchell Sabrina L, Farber-Eger Eric H, Veatch Olivia J, Wheeler Nicholas R, Goodloe Robert J, Wells Quinn S, Murdock Deborah G, Crawford Dana C
Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
PeerJ. 2018 Jun 25;6:e5149. doi: 10.7717/peerj.5149. eCollection 2018.
Effective approaches for assessing mitochondrial DNA (mtDNA) variation are important to multiple scientific disciplines. Mitochondrial haplogroups characterize branch points in the phylogeny of mtDNA. Several tools exist for mitochondrial haplogroup classification. However, most require full or partial mtDNA sequence which is often cost prohibitive for studies with large sample sizes. The purpose of this study was to develop Hi-MC, a high-throughput method for mitochondrial haplogroup classification that is cost effective and applicable to large sample sizes making mitochondrial analysis more accessible in genetic studies. Using rigorous selection criteria, we defined and validated a custom panel of mtDNA single nucleotide polymorphisms that allows for accurate classification of European, African, and Native American mitochondrial haplogroups at broad resolution with minimal genotyping and cost. We demonstrate that Hi-MC performs well in samples of European, African, and Native American ancestries, and that Hi-MC performs comparably to a commonly used classifier. Implementation as a software package in R enables users to download and run the program locally, grants greater flexibility in the number of samples that can be run, and allows for easy expansion in future revisions. Hi-MC is available in the CRAN repository and the source code is freely available at https://github.com/vserch/himc.
评估线粒体DNA（mtDNA）变异的有效方法对多个科学学科都很重要。线粒体单倍群表征了mtDNA系统发育中的分支点。现有多种用于线粒体单倍群分类的工具。然而，大多数工具需要完整或部分mtDNA序列，这对于大样本量的研究来说成本往往过高。本研究的目的是开发Hi-MC，一种用于线粒体单倍群分类的高通量方法，该方法具有成本效益且适用于大样本量，使得线粒体分析在基因研究中更容易实现。我们使用严格的选择标准，定义并验证了一个定制的mtDNA单核苷酸多态性面板，该面板能够以最小的基因分型和成本在广泛分辨率下准确分类欧洲、非洲和美洲原住民的线粒体单倍群。我们证明Hi-MC在欧洲、非洲和美洲原住民血统的样本中表现良好，并且与常用的分类器表现相当。作为R语言中的软件包实现，用户可以在本地下载并运行该程序，在可运行的样本数量上具有更大的灵活性，并且便于在未来版本中轻松扩展。Hi-MC可在CRAN存储库中获取，其源代码可在https://github.com/vserch/himc上免费获取。
