MITOMASTER: a bioinformatics tool for the analysis of mitochondrial DNA sequences

Abstract

We have developed a computer system, MITOMASTER, to make analysis of human mitochondrial DNA (mtDNA) sequences efficient, accurate, and easily available. From imported sequences, the system identifies nucleotide variants, determines the haplogroup, rules out possible pseudogene contamination, identifies novel DNA sequence variants, and evaluates the potential biological significance of each variant. This system should be beneficial for mtDNA analyses of biomedical physicians and investigators, population biologists and forensic scientists. MITOMASTER can be accessed at http://mammag.web.uci.edu/twiki/bin/view/Mitomaster.

Figure 1

The algorithm used by biologist, and implemented within MITOMASTER, to identify possible clinical variants within a patient's mtDNA sequence. Variants are extracted by alignment with a reference sequence; the group of extracted variants is used to determine the haplogroup of the sequence and each individual variant is checked within the database and analyzed to determine its biological effect; variation within coding loci is further analyzed to determine its coding effect and inter-species rate of conservation.

Figure 2

MITOMASTER's functional components. A website interface allows users to submit either files of whole mtDNA sequences or individual variants for analysis. Programs within the analysis component compare the submission with the mCRS, extract the variants found within submitted sequences, perform NUMT screening on the variants extracted, assign the sequences to a haplogroup, and determine the predicted functional effect of each variant.

Figure 3

Simplified schema diagram for MITOMASTER's database. DNA sequences are decomposed into their constituent nucleic acids and entries made in the dna table. During simulated transcription and translation processes, all variation (relative to the mCRS) is entered into the rna and aa tables, respectively. Some variation involves multiple base alterations and these cases are grouped in the “variant” table. The aggregated variants that define the known haplogroups are represented in the haplogroups data set, the nodes are the branch points of the mtDNA phylogenetic tree.