MMDIT: A tool for the deconvolution and interpretation of mitochondrial DNA mixtures

A New Tool for Probabilistic Assessment of MPS Data Associated with mtDNA Mixtures

“…The historic limitation of traditional mtDNA typing has been a lower discrimination potential created by a combination of uniparental inheritance of the mitochondrial (mito) genome and limited resolution of mixtures associated with Sanger sequencing. The increased sensitivity currently achievable with massively parallel sequencing (MPS) enables accurate characterization and reporting of intrinsic, low-level sequence mitogenome variants [3][4][5][6][7], and an advantage of uniparental inheritance is an expectation that the majority of individuals will only contribute one haplotype to a mixed sample making mtDNA an attractive aid in the assessment of mixed DNA samples [2,[8][9][10].…”

“…An overview by Coble and Bright [17], focusing on autosomal mixture interpretation using probabilistic approaches noted, "there is a strong need to apply probabilistic methods to interpreting mixtures with haploid marker systems", such as mtDNA. To date, little work has been done to deconvolute mixtures of mtDNA sequence from MPS data [2,8,18,19]. The availability of MPS mtDNA data presents an opportunity to shift this paradigm.…”

“…This approach showed promise but as noted by the authors, "mtDNA mixture analysis will become more effective and efficient with advances in bioinformatics pipelines". UNT made subsequent advancements in developing pipelines using approaches focused on population and statistical phasing [8,9]. The mitochondrial mixture deconvolution and interpretation tool (MMDIT) is an open-source software that automates mixture deconvolution [8], but the shiny app is tailored to data generated using the Ion S5 and Converge software (ThermoFisher, Waltham, MA, USA) making it less user-friendly for data generated on an Illumina MiSeq or other sequencing platforms.…”

“…UNT made subsequent advancements in developing pipelines using approaches focused on population and statistical phasing [8,9]. The mitochondrial mixture deconvolution and interpretation tool (MMDIT) is an open-source software that automates mixture deconvolution [8], but the shiny app is tailored to data generated using the Ion S5 and Converge software (ThermoFisher, Waltham, MA, USA) making it less user-friendly for data generated on an Illumina MiSeq or other sequencing platforms. The second group developed an advanced bioinformatic approach to deconvoluting complex mtDNA mixtures from MPS data using phylogenetic information [2].…”

Post hoc deconvolution of human mitochondrial DNA mixtures by EMMA 2 using fine-tuned Phylotree nomenclature

“…In this study we developed and evaluated a strategy to deconvolute mtDNA mixtures using phylogenetic principles. Earlier attempts to separate human mtDNA mixtures applied physical methods, such as denaturing high-performance liquid chromatography [6] , [18] , base composition profiling using mass spectrometry [12] , quantitative data in a statistical framework [9] and MPS-based data [5] , [13] , [21] with a continuous statistical phasing framework [28] . While some of these strategies have proven useful, there is still a lack of technology-agnostic, non-quantitative and easy to use mtDNA mixture deconvolution tools that provide traceable splittings on any kind of sequencing data (Sanger and MPS).…”