The Aldehyde Dehydrogenase Gene Superfamily Resource Center
© Henry Stewart Publications 2009
Received: 23 October 2009
Accepted: 23 October 2009
Published: 1 December 2009
The website http://www.aldh.org is a publicly available database for nomenclature and functional and molecular sequence information for members of the aldehyde dehydrogenase (ALDH) gene superfamily for animals, plants, fungi and bacteria. The site has organised gene-specific records. It provides synopses of ALDH gene records, marries trivial terms to correct nomenclature and links global accession identifiers with source data. Server-side alignment software characterises the integrity of each sequence relative to the latest genomic assembly and provides identifier-specific detail reports, including a graphical presentation of the transcript's exon - intron structure, its size, coding sequence, genomic strand and locus. Also included are a summary of substrates, inhibitors and enzyme kinetics. The site provides reference lists and is designed to facilitate data mining by interested investigators.
The completion of various genome projects and the growing trend towards high-throughput data production have created a significant knowledge base of molecular sequence data across a broad spectrum of species. This increase in available sequence information has led to a widening gap between the available raw sequence data and their functional analyses by molecular biological methods or other genetic approaches. As a consequence, the field of bioinformatics has rapidly developed as an essential aid for data analysis. A number of large-scale, gene-specific databases, including the National Center for Biotechnology Information (NCBI)'s Entrez Gene and the European Bioinformatics Institute/Wellcome Trust Sanger Institute's Ensembl databases, have developed to report and catalogue molecular sequence data. The intrinsic format of these databases in attempting to cover all genes for all species or to cover all genes for a given species (eg the mouse genome database), however, has significant limitations. These include errors in sequence alignments due to a reliance on automated algorithms, poorly defined reference sequences and improper gene nomenclature. Other issues include lack of identification and/or categorisation of alternatively spliced transcriptional variants, as well as erroneous functional characterisations because generalised gene ontology entries do not distinguish the individual gene from other members of its gene superfamily. To address these limitations, we have developed a gene-specific database architecture and web-based scripting system which is tailored to report both the molecular sequence and functional data for all members of an individual gene superfamily across all species (Black and Vasiliou, manuscript in preparation). Using this software and relational database architecture, we have developed http://www.aldh.org, a publicly available informational resource system for all members of the aldehyde dehydrogenase (ALDH) gene superfamily. The ALDH gene superfamily is an evolutionarily ancient group of genes spanning all the kingdoms and phyla known today. The ALDH website is designed to provide a comprehensive 'gold standard' dataset across a variety of species for the molecular and functional information pertaining to members of this superfamily.
Site design, hosting and software
The http://www.aldh.org website is designed, hosted and curated by the authors and is currently hosted at the University of Colorado's Anschutz campus in Denver, CO, USA. To accommodate various hosting platforms, the site's software infrastructure is capable of running on Microsoft Windows Server or Linux platforms running Internet Information Services 5 or higher (Microsoft) or Apache website hosting software. The site database operates on the open-source database software MySQL (version 5.0.51a) and content is dynamically generated via server-side scripting using the open-source script engine, PHP (version 5.2.9-2).
Organisation of the web database
From its launch in 1999, the ALDH gene superfamily website has grown exponentially and continues to do so as more genome projects are completed and become openly accessible. The http://www.aldh.org website provides comprehensive access to molecular, functional and bibliographic elements for each ALDH in the gene superfamily for human, mouse and rat. Additional superfamily data for other animal species, as well as for plants, bacteria and fungi, are regularly incorporated into the database and presented as completed.
The website's homepage welcomes users with regularly updated news and information about members of the superfamily, as well as any newly available site features. It displays a 'record status' summary table totalling the number of ALDH gene superfamily members within each species and quick links to each of the respective gene records within the database. The website's global navigation bar is located along the top of the homepage and allows visitors easily to access the 'ALDH overview' section, providing a general history and review of the ALDH gene superfamily and its nomenclature system. The 'ALDH gene superfamily' link provides a complete tabular summary of all ALDH genes, with navigational links to all relevant records within the database. The 'ALDH publications' section displays a comprehensive reference list for the ALDH gene superfamily, sorted by ALDH subfamily and gene. A 'Links' page contains datamining sources and toolsets, and a 'Laboratory' page describes our personnel and their respective research interests. A local navigation system is situated on the left-hand side of each page within the http://www.aldh.org website, to enable users quickly to scroll their web browsers within the current page being viewed to pre-defined bookmarked subsections. Therefore, the global and local navigation systems provide users with a simple and uniform structure throughout the site, enabling ease of access to all database information.
The core functionality of the site is structured around the gene-specific records for each ALDH within the gene superfamily. All database information for each ALDH gene record is dynamically generated, organised and displayed to the user's web browser by the website's server-side scripting engine in a clear, concise and user-friendly approach.
Each gene-specific record is derived from a global template, utilising a series of curator-specified software data modules tailored to the ALDH gene superfamily. These modules perform pre-defined database queries and generate all of a record's text, tables and graphical representations for the end-user's web browser. At the time of writing, software data modules registered in this global template generate the 'Synopses', 'Trivial names', 'Global accession identifiers', 'Molecular features and cataloguing', 'Accession identifier details', 'Human polymorphisms', 'Enzyme kinetics', 'Tissue expression profiles' and 'Reference list' sections for each ALDH gene.
ALDH gene records begin with a living review of the literature, prepared and regularly updated by the authors, describing available structural and functional data. All information and illustrations are referenced to the original publication using hyperlinked PubMed database identifiers (PMID). In addition, details for each reference are further described within the reference list section of the record.
Members of the ALDH gene superfamily have had a number of descriptive synonyms used in the literature over the past three decades. This section associates these synonyms with their corresponding nomenclature.
Global accession identifiers
Accession identifiers for a given ALDH gene, transcript or peptide sequence are numerous due to the multitude of disparate databases providing molecular sequence data. The 'Global accession identifiers' module tabulates these accessions into hyperlinked identifiers to all source databases. This enables users quickly to access all source data for an individual ALDH member.
Molecular features and cataloguing
Accession identifier detail reports
Substrates, inhibitors and enzyme kinetics
Characterisation of ALDH gene superfamily members typically includes their enzymatic activity for an assortment of substrates and inhibitors using various test systems, isolation techniques, cofactors, tissues and species origin. This module provides a tabular summary of the literature for all reported kinetics values, sorted by species. Each entry includes the hyperlinked PubMed identifier to the original literature source for quick accessibility.
References to the original sources for all data within the http://www.aldh.org database are an important priority for the ALDH gene superfamily curators. The reference list module provides a bibliography for all data reported within each gene-specific record, including those from the 'Synopsis and substrates', and 'Inhibitors and enzyme kinetics' modules, as well as additional references recommended by the curators. All references within this section are hyperlinked to the PubMed database via the PMID for ease of access.
Data mining and processing
The http://www.aldh.org website is an ongoing project which enables the Vasiliou laboratory to maintain a living review of all ALDH genes, as well as provide detailed functional and molecular sequence analysis to the public. New ALDH genes and existing ALDH gene orthologues are continually being added as genome projects are completed. This site's identification and characterisation of the ALDH gene superfamily members will provide investigators with a degree of consistency in terms of HUGO-approved nomenclature as they report their findings in the future. The server-side data modules producing the website are frequently updated for increased performance or additional data analysis, and new modules are designed and produced as an area of interest becomes apparent. At the time of writing, the authors are designing four additional gene record modules to address and characterise: (a) human polymorphisms from the NCBI dbSNP database; (b) subcellular localisation and tissue expression profiles; (c) upstream binding elements and promoters for each gene member; and (d) incorporation of the AmiGO gene ontology features. Lastly, it is our hope that users find this site helpful in their search for information and that investigators embarking on future gene superfamily initiatives utilise our site's structure and format in reporting such data to the web. The authors welcome all feedback regarding the website, as well as any ideas for new data modules that we have not yet addressed.
We thank our colleagues for valuable discussions and a careful reading of this manuscript. This work was supported, in part, by NIH grants EY17963 and AA017754.
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