HmtDB, a human mitochondrial genomic resource based on variability studies supporting population genetics and biomedical research

Abstract

Background: Population genetics studies based on the analysis of mtDNA and mitochondrial disease studies have produced a huge quantity of sequence data and related information. These data are at present worldwide distributed in differently organised databases and web sites not well integrated among them. Moreover it is not generally possible for the user to submit and contemporarily analyse its own data comparing them with the content of a given database, both for population genetics and mitochondrial disease data.

Results: HmtDB is a well-integrated web-based human mitochondrial bioinformatic resource aimed at supporting population genetics and mitochondrial disease studies, thanks to a new approach based on site-specific nucleotide and aminoacid variability estimation. HmtDB consists of a database of Human Mitochondrial Genomes, annotated with population data, and a set of bioinformatic tools, able to produce site-specific variability data and to automatically characterize newly sequenced human mitochondrial genomes. A query system for the retrieval of genomes and a web submission tool for the annotation of new genomes have been designed and will soon be implemented. The first release contains 1255 fully annotated human mitochondrial genomes. Nucleotide site-specific variability data and multialigned genomes can be downloaded. Intra-human and inter-species aminoacid variability data estimated on the 13 coding for proteins genes of the 1255 human genomes and 60 mammalian species are also available. HmtDB is freely available, upon registration, at http://www.hmdb.uniba.it.

Conclusion: The HmtDB project will contribute towards completing and/or refining haplogroup classification and revealing the real pathogenic potential of mitochondrial mutations, on the basis of variability estimation.

Figure 1

HmtDB query pages. Design of pages related to Query function as it will be implemented in the database. a) Multicriterion query form. b) Example of a query result.

Figure 2

HmtDB relational database. HmtDB relational structure includes 24 tables, storing complete set of HmtDB data linked to each other.

Figure 3

Variability Generation Work Flow (VGWF). Starting from the multialignment of all the genomes stored in the database and of continent-specific subsets performed with MAFFT program, three variability analyses are executed separately: nucleotide variability values for both the entire set of genomes and the continent-specific subsets are estimated through SiteVar program applied on real dataset (right hand side of the Work Flow) and on 100 simulated multialignments obtained through an automatic procedure for each continent-specific genomes dataset (in the middle of the Work Flow); aminoacid variability data (left hand side of the Work Flow) are produced by applying MitVarProt software to the 13 multialigned mitochondrial protein coding genes, automatically selected from the entire starting nucleotide multialignment and translated into aminoacid sequences through TRANSEQ program; the data produced through this three procedures are inserted in NT_VARIABILITY, NT_VARIABILITY_SIM and AA_VARIABILITY tables of the relational HmtDB structure respectively.