MToolBox

MToolBox reconstructs and analyzes human mitochondrial DNA (mtDNA) from high-throughput sequencing data such as whole-exome sequencing (WXS) and whole-genome sequencing (WGS) to quantify heteroplasmy and identify functionally significant mitochondrial variants.

Key Features:

• Automated Reconstruction: Automates assembly of mitochondrial genomes from high-throughput sequencing data including WXS and WGS.
• Heteroplasmy Measurement: Provides quantification of heteroplasmy levels, including allele-specific heteroplasmy information.
• Haplogroup Assignment: Assigns mitochondrial haplogroups for population and evolutionary analyses.
• Variant Prioritization: Performs prioritization analysis to identify functionally important mtDNA variants.
• Output Formats: Produces Variant Call Format (VCF) files with allele-specific heteroplasmy and annotation files with prioritized variants.

Scientific Applications:

• Mitochondrial disease research: Detection and quantification of heteroplasmic and homoplasmic variants relevant to mitochondrial diseases.
• Aging research: Study of mtDNA variation and heteroplasmy dynamics in aging.
• Metabolic disorder studies: Identification of mtDNA variants implicated in metabolic disorders.
• Evolutionary and population genetics: Haplogroup assignment and variant data for tracing evolutionary lineages and population structure.

Methodology:

Computational steps explicitly include assembly of mitochondrial genomes, quantification of allele-specific heteroplasmy, haplogroup assignment, and generation of VCF and annotation files; the pipeline was tested on simulated samples and applied to 1000 Genomes Project WXS datasets.