HmtDB

HmtDB provides a curated database of human mitochondrial genome sequences and associated variability annotations to support population genetics, haplogroup classification, and assessment of mtDNA mutation pathogenicity.

Key Features:

• Database content: Hosts an extensive collection of human mitochondrial genomes, including sequences from individuals with both healthy and disease phenotypes to facilitate pathogenicity assessment.
• Data sources: Integrates sequence data from INSDC databases and personal submissions.
• NGS processing with MToolBox: Applies MToolBox for reconstruction and analysis of human mitochondrial DNA from next-generation sequencing (NGS) data and supports a command-line stand-alone implementation.
• Reference sequence (RSRS): Implements the Reconstructed Sapiens Reference Sequence (RSRS) as the analysis reference.
• Annotation and variability metrics: Provides manually curated annotations with population and variability data, with site-specific nucleotide and amino acid variability estimated by SiteVar.
• Haplogroup prediction: Includes Phylotree-based classifier tools for haplogroup assignment and a fragment-classifier for partial sequences.
• Alignments and variability datasets: Supplies multi-alignments with reference genomes together with variability datasets for comparative analyses.
• Cross-species variability analysis: Contains intra-human and inter-species amino acid variability estimated from 13 mitochondrial protein-coding genes across human genomes and 60 mammalian species.

Scientific Applications:

• Haplogroup classification and refinement: Enables assignment and refinement of mitochondrial haplogroups using Phylotree-based classifiers.
• Pathogenicity assessment: Supports evaluation of the pathogenic potential of mtDNA mutations by comparing sequence and variability data across healthy and disease phenotypes.
• Population genetics and comparative analyses: Facilitates population genetic studies and comparative analyses using multi-alignments, population annotations, and site-specific variability metrics.
• Evolutionary and functional inference: Supports evolutionary conservation and functional impact analyses across mammals using inter-species amino acid variability from 13 protein-coding genes.

Methodology:

Sequence data are integrated from INSDC databases and personal submissions, and NGS data are processed with MToolBox; SiteVar estimates site-specific nucleotide and amino acid variability; haplogroup assignment uses Phylotree-based classifiers; amino acid variability is estimated from 13 mitochondrial protein-coding genes across human and 60 mammalian species.