mtDNA-Server

mtDNA-Server detects heteroplasmic variants in mitochondrial DNA and distinguishes genuine mitochondrial variation from contamination to support studies in population genetics, evolutionary biology, and disease research.

Key Features:

• Heteroplasmy Detection: Identifies heteroplasmic variants representing intra-individual sequence variation within mtDNA.
• Contamination Deconvolution: Uses haplogroup-based methods to deconvolute contamination from genuine heteroplasmic variants.
• Parallel Processing with Hadoop MapReduce: Parallelizes read alignment, variant detection, and quality control using the Hadoop MapReduce framework for scalable analysis.
• Quality Control Metrics: Reports multiple quality control metrics that address issues commonly overlooked in mtDNA NGS studies.
• Scalability and Performance: Validated on large datasets, including analysis of the 1000 Genomes Project Phase 3 data (n = 2,504) in under five hours.

Scientific Applications:

• Genetic Research: Investigating mtDNA variants and heteroplasmy in genetic disorders, with detection of heteroplasmies and artificial recombinations down to 1% with perfect specificity.
• Evolutionary Studies: Tracing maternal lineages and reconstructing evolutionary history using mitochondrial markers.
• Forensic Science: Analyzing mtDNA for identification and casework where contamination control and deconvolution are critical.

Methodology:

Workflow comprises parallel read alignment followed by heteroplasmy detection, artifact and contamination identification, haplogroup-based contamination deconvolution, variant annotation, and quality-control reporting, with computational steps parallelized using Hadoop MapReduce; validation used artificial sample mix-ups on two different NGS devices.