Abstract
BackgroundWhole genome and exome sequencing usually include reads containing mitochondrial DNA (mtDNA). Yet, state-of-the-art pipelines and services for human nuclear genome variant calling and annotation do not handle mitochondrial genome data appropriately. As a consequence, any researcher desiring to add mtDNA variant analysis to their investigations is forced to explore the literature for mtDNA pipelines, evaluate them, and implement their own instance of the desired tool. This task is far from trivial, and can be prohibitive for non-bioinformaticians.ResultsWe have developed SG-ADVISER mtDNA, a web server to facilitate the analysis and interpretation of mtDNA genomic data coming from next generation sequencing (NGS) experiments. The server was built in the context of our SG-ADVISER framework and on top of the MtoolBox platform (Calabrese et al., Bioinformatics 30(21):3115–3117, 2014), and includes most of its functionalities (i.e., assembly of mitochondrial genomes, heteroplasmic fractions, haplogroup assignment, functional and prioritization analysis of mitochondrial variants) as well as a back-end and a front-end interface. The server has been tested with unpublished data from 200 individuals of a healthy aging cohort (Erikson et al., Cell 165(4):1002–1011, 2016) and their data is made publicly available here along with a preliminary analysis of the variants. We observed that individuals over ~90 years old carried low levels of heteroplasmic variants in their genomes.ConclusionsSG-ADVISER mtDNA is a fast and functional tool that allows for variant calling and annotation of human mtDNA data coming from NGS experiments. The server was built with simplicity in mind, and builds on our own experience in interpreting mtDNA variants in the context of sudden death and rare diseases. Our objective is to provide an interface for non-bioinformaticians aiming to acquire (or contrast) mtDNA annotations via MToolBox. SG-ADVISER web server is freely available to all users at https://genomics.scripps.edu/mtdna.
Highlights
Whole genome and exome sequencing usually include reads containing mitochondrial Deoxyribonucleic acid (DNA)
We present SG-ADVISER mtDNA, a web server built on top of MToolBox, that attempts to simplify the human mitochondrial DNA variant calling, annotation and interpretation of variants
We extracted mtDNA reads from Whole genome sequencing (WGS) Binary Sequence alignment/map format (SAM) format (BAM) files to create mtDNA-only BAM files that were later submitted to our server
Summary
Whole genome and exome sequencing usually include reads containing mitochondrial DNA (mtDNA). Generation Sequencing (NGS) technologies are revealing the complexity and richness of the human genome While this revolution is blooming for nuclear DNA, much remains to be built out and matured for the 16,569 base pairs of the human mitochondrial genome (mtDNA), in particular for functional annotations of disease associated variants. We envision that in the future an individual may be sequenced several times (at the tissue level) to develop a more accurate picture of the expected severity and tissue specificity of a suspected mitochondrial disease. For all these reasons, there is a need for robust bioinformatic analysis of mtDNA variants
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