mity

mity detects and interprets heteroplasmic single nucleotide variants (SNVs) and insertions/deletions (INDELs) in the mitochondrial genome from whole genome sequencing (WGS) data to improve identification of pathogenic mitochondrial variants.

Key Features:

• High Sensitivity and Specificity: Leverages the high mitochondrial coverage achievable in WGS of blood (average 3,166×) to detect pathogenic heteroplasmic SNVs and INDELs at low allelic fractions.
• Integration with Diagnostic Pipelines: Can be incorporated into existing diagnostic WGS pipelines for analysis of mitochondrial variants associated with mitochondrial diseases and impaired mitochondrial function.
• Command-line Calling and Normalization: Supports running mity call and mity normalise separately or together using the --normalise option to produce normalized VCF files for downstream analysis.
• Variant Interpretation: Provides functionalities to assist interpretation of mitochondrial variants to assess potential pathogenicity.

Scientific Applications:

• Clinical diagnosis of mitochondrial disease: Enables detection and interpretation of heteroplasmic mitochondrial variants to aid diagnosis amid genotype–phenotype heterogeneity.
• Non-invasive variant detection from blood: Facilitates identification of low-heteroplasmy mitochondrial variants in blood WGS, reducing reliance on invasive tissue biopsies and potentially increasing diagnostic yield.

Methodology:

Utilizes unbiased WGS data to analyze both nuclear and mitochondrial genomes, employing an algorithm tailored to overcome limitations of conventional nuclear variant detection methods that often fail to identify low heteroplasmy variants, and capitalizes on high mitochondrial coverage (≈3,166×) from WGS to enhance sensitivity.