mitoAnalyzer

A software package for analysis of mitochondrial DNA using sequencing data
Contains mitoCaller and mitoCalc/fastMitoCalc

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Overview

mitoAnalyzer is a software package that provides a general approach for the analysis of mitochondrial DNA (mtDNA) in next-generation sequencing studies, using whole-genome sequencing data. It has two components, mitoCaller and mitoCalc/fastMitoCalc

mitoCaller

Identification of mtDNA single nucleotide variants (homoplasmies and heteroplasmies) mitoCaller identified mtDNA single nucleotide variants (homoplasmies and heteroplasmies) by incorporating sequencing error rates at each base in a likelihood calculation and allows allele fractions at a variant site to differ among individuals. It relies on the genotype likelihood calculation described in the graphic below:

Genotype Likelihood Calculation

mitoCalc and fastMitoCalc

mitoCalc and fastMitoCalc use whole-genome sequencing data to estimate mtDNA copy based on the observed ratio of sequencing coverage between mtDNA and autosomal DNA

fastMitoCalc is an upgraded version of mitoCalc that estimates mtDNA copy number quickly and accurately (99% correlation with mitoCalc, over 100x faster) using a randomly selected group of short autosomal DNA sequences (default is 3,000 regions of length 1kb) rather than the entire autosomal genome to estimate autosomal DNA sequencing coverage. fastMitoCalc can rapidly analyze hundreds of thousands of genomes, thereby facilitating association studies of mtDNA copy number with quantitative traits or autosomal DNA variants.

Method for mitoCalc and fastMitoCalc

Comparison between mitoCalc and fastMitoCalc

Program | Nuclear Genome Used as Reference | Total Length of Nuclear Genome Considered | Computing Time: 1 Sample at 4x Coverage, 1 CPU | Computing Time: 50,000 Samples at 30x Coverage, 500 CPUs :---: | :---: | :---: | :---: | :---: mitoCalc | Whole genome | 3.2 billion bases | 3 hours | 3 months fastMitoCalc | 3,000 1kb fragments (default setting) | 3 million bases | 59 seconds | 12.5 hours

fastMitoCalc is over 180x faster than mitoCalc using default settings!

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Current Directions

The software package was originally developed to analyze whole-genome sequencing data. We are actively investigating its applicability to exome-sequencing data.

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Citation

Ding J*, Sidore C, Butler TJ, Wing MK, Qian Y, Meirelles O, Busonero F, Tsoi LC, Maschio A, Angius A, Kang HM, Nagaraja R, Cucca F, Abecasis GR, Schlessinger D* (2015). Assessing mitochondrial DNA variation and copy number in lymphocytes of ~2,000 Sardinians using tailored sequencing analysis tools. PLoS Genetics 11(7): e1005306. *corresponding author
Link to article

Qian Y, Butler TJ, Opsahl-Ong K, Giroux N, Sidore C, Nagaraja R, Cucca F, Ferrucci L, Abecasis GR, Schlessinger D, Ding J*(2017). fastMitoCalc: an ultra-fast program to estimate mitochondrial DNA copy number from whole-genome sequences. Bioinformatics.
*corresponding author
Link to article

Last update: April 14, 2017

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Contact Information

Questions and Help Requests

If you have any bug reports or questions please send an email to Jun Ding: jun.ding@nih.gov

Jun Ding, Ph.D.
Staff Scientist
Translational Gerontology Branch
National Institute on Aging, NIH
251 Bayview Blvd, Ste 100, Rm 10B123
Baltimore, MD, 21224