The metabolome refers to the complete set of small-molecule chemicals found within a biological sample. The biological sample can be a cell, a cellular organelle, an organ, a tissue, a tissue extract, a biofluid or an entire organism. The small molecule chemicals found in a given metabolome may include both endogenous metabolites that are naturally produced by an organism as well as exogenous chemicals that are not naturally produced by an organism.
The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets created and maintained by the University of Alberta and The Metabolomics Innovation Centre located in Alberta, Canada. As both a bioinformatics and a cheminformatics resource, DrugBank combines detailed drug data with comprehensive drug target information. DrugBank has used content from Wikipedia; Wikipedia also often links to Drugbank, posing potential circular reporting issues.
Amos Bairoch is a Swiss bioinformatician and Professor of Bioinformatics at the Department of Human Protein Sciences of the University of Geneva where he leads the CALIPHO group at the Swiss Institute of Bioinformatics (SIB) combining bioinformatics, curation, and experimental efforts to functionally characterize human proteins.
Orciprenaline, also known as metaproterenol, is a bronchodilator used in the treatment of asthma. Orciprenaline is a moderately selective β2 adrenergic receptor agonist that stimulates receptors of the smooth muscle in the lungs, uterus, and vasculature supplying skeletal muscle, with minimal or no effect on α adrenergic receptors. The pharmacologic effects of β adrenergic agonist drugs, such as orciprenaline, are at least in part attributable to stimulation through β adrenergic receptors of intracellular adenylyl cyclase, the enzyme which catalyzes the conversion of ATP to cAMP. Increased cAMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from many cells, especially from mast cells.
PDBsum is a database that provides an overview of the contents of each 3D macromolecular structure deposited in the Protein Data Bank. The original version of the database was developed around 1995 by Roman Laskowski and collaborators at University College London. As of 2014, PDBsum is maintained by Laskowski and collaborators in the laboratory of Janet Thornton at the European Bioinformatics Institute (EBI).
The Human Metabolome Database (HMDB) is a comprehensive, high-quality, freely accessible, online database of small molecule metabolites found in the human body. It bas been created by the Human Metabolome Project funded by Genome Canada and is one of the first dedicated metabolomics databases. The HMDB facilitates human metabolomics research, including the identification and characterization of human metabolites using NMR spectroscopy, GC-MS spectrometry and LC/MS spectrometry. To aid in this discovery process, the HMDB contains three kinds of data: 1) chemical data, 2) clinical data, and 3) molecular biology/biochemistry data (Fig. 1–3). The chemical data includes 41,514 metabolite structures with detailed descriptions along with nearly 10,000 NMR, GC-MS and LC/MS spectra.
The Toxin and Toxin-Target Database (T3DB), also known as the Toxic Exposome Database, is a freely accessible online database of common substances that are toxic to humans, along with their protein, DNA or organ targets. The database currently houses nearly 3,700 toxic compounds or poisons described by nearly 42,000 synonyms. This list includes various groups of toxins, including common pollutants, pesticides, drugs, food toxins, household and industrial/workplace toxins, cigarette toxins, and uremic toxins. These toxic substances are linked to 2,086 corresponding protein/DNA target records. In total there are 42,433 toxic substance-toxin target associations. Each toxic compound record (ToxCard) in T3DB contains nearly 100 data fields and holds information such as chemical properties and descriptors, mechanisms of action, toxicity or lethal dose values, molecular and cellular interactions, medical information, NMR an MS spectra, and up- and down-regulated genes. This information has been extracted from over 18,000 sources, which include other databases, government documents, books, and scientific literature.
The Small Molecule Pathway Database (SMPDB) is a comprehensive, high-quality, freely accessible, online database containing more than 600 small molecule (i.e. metabolic) pathways found in humans. SMPDB is designed specifically to support pathway elucidation and pathway discovery in metabolomics, transcriptomics, proteomics and systems biology. It is able to do so, in part, by providing colorful, detailed, fully searchable, hyperlinked diagrams of five types of small molecule pathways: 1) general human metabolic pathways; 2) human metabolic disease pathways; 3) human metabolite signaling pathways; 4) drug-action pathways and 5) drug metabolism pathways. SMPDB pathways may be navigated, viewed and zoomed interactively using a Google Maps-like interface. All SMPDB pathways include information on the relevant organs, subcellular compartments, protein cofactors, protein locations, metabolite locations, chemical structures and protein quaternary structures (Fig. 1). Each small molecule in SMPDB is hyperlinked to detailed descriptions contained in the HMDB or DrugBank and each protein or enzyme complex is hyperlinked to UniProt. Additionally, all SMPDB pathways are accompanied with detailed descriptions and references, providing an overview of the pathway, condition or processes depicted in each diagram. Users can browse the SMPDB (Fig. 2) or search its contents by text searching (Fig. 3), sequence searching, or chemical structure searching. More powerful queries are also possible including searching with lists of gene or protein names, drug names, metabolite names, GenBank IDs, Swiss-Prot IDs, Agilent or Affymetrix microarray IDs. These queries will produce lists of matching pathways and highlight the matching molecules on each of the pathway diagrams. Gene, metabolite and protein concentration data can also be visualized through SMPDB's mapping interface.
MetaboAnalyst is a set of online tools for metabolomic data analysis and interpretation, created by members of the Wishart Research Group at the University of Alberta. It was first released in May 2009 and version 2.0 was released in January 2012. MetaboAnalyst provides a variety of analysis methods that have been tailored for metabolomic data. These methods include metabolomic data processing, normalization, multivariate statistical analysis, and data annotation. The current version is focused on biomarker discovery and classification.
The European Nucleotide Archive (ENA) is a repository providing free and unrestricted access to annotated DNA and RNA sequences. It also stores complementary information such as experimental procedures, details of sequence assembly and other metadata related to sequencing projects. The archive is composed of three main databases: the Sequence Read Archive, the Trace Archive and the EMBL Nucleotide Sequence Database. The ENA is produced and maintained by the European Bioinformatics Institute and is a member of the International Nucleotide Sequence Database Collaboration (INSDC) along with the DNA Data Bank of Japan and GenBank.
Forasartan, otherwise known as the compound SC-52458, is a nonpeptide angiotensin II receptor antagonist (ARB, AT1 receptor blocker).
5-Androstenedione, also known as androst-5-ene-3,17-dione, is a prohormone of testosterone. The World Anti-Doping Agency prohibits its use in athletes. In the United States, it is a controlled substance.
Metabolite Set Enrichment Analysis (MSEA) is a method designed to help metabolomics researchers identify and interpret patterns of metabolite concentration changes in a biologically meaningful way. It is conceptually similar to another widely used tool developed for transcriptomics called Gene Set Enrichment Analysis or GSEA. GSEA uses a collection of predefined gene sets to rank the lists of genes obtained from gene chip studies. By using this “prior knowledge” about gene sets researchers are able to readily identify significant and coordinated changes in gene expression data while at the same time gaining some biological context. MSEA does the same thing by using a collection of predefined metabolite pathways and disease states obtained from the Human Metabolome Database. MSEA is offered as a service both through a stand-alone web server and as part of a larger metabolomics analysis suite called MetaboAnalyst.
BASys is a freely available web server that can be used to perform automated, comprehensive annotation of bacterial genomes. With the advent of next generation DNA sequencing it is now possible to sequence the complete genome of a bacterium within a single day. This has led to an explosion in the number of fully sequenced microbes. In fact, as of 2013, there were more than 2700 fully sequenced bacterial genomes deposited with GenBank. However, a continuing challenge with microbial genomics is finding the resources or tools for annotating the large number of newly sequenced genomes. BASys was developed in 2005 in anticipation of these needs. In fact, BASys was the world’s first publicly accessible microbial genome annotation web server. Because of its widespread popularity, the BASys server was updated in 2011 through the addition of multiple server nodes to handle the large number of queries it was receiving.
BacMap is a freely available web-accessible database containing fully annotated, fully zoomable and fully searchable chromosome maps from more than 2500 prokaryotic species. BacMap was originally developed in 2005 to address the challenges of viewing and navigating through the growing numbers of bacterial genomes that were being generated through large-scale sequencing efforts. Since it was first introduced, the number of bacterial genomes in BacMap has grown by more than 15X. Essentially BacMap functions as an on-line visual atlas of microbial genomes. All of the genome annotations in BacMap were generated through the BASys genome annotation system. BASys is a widely used microbial annotation infrastructure that performs comprehensive bioniformatic analyses on raw bacterial genome sequence data. All of the genome (chromosome) maps in BacMap were constructed using the program known as CGView. CGView is a popular visualization program for generating interactive, web-compatible circular chromosome maps. Each chromosome map in BacMap is extensively hyperlinked and each chromosome image can be interactively navigated, expanded and rotated using navigation buttons or hyperlinks. All identified genes in a BacMap chromosome map are colored according to coding directions and when sufficiently zoomed-in, gene labels are visible. Each gene label on a BacMap genome map is also hyperlinked to a 'gene card'. The gene cards provide detailed information about the corresponding DNA and protein sequences. Each genome map in BacMap is searchable via BLAST and a gene name/synonym search.
FooDB is a freely available, open-access database containing chemical composition data on common, unprocessed foods. It also contains extensive data on flavour and aroma constituents, food additives as well as positive and negative health effects associated with food constituents. The database contains information on more than 28,000 chemicals found in more than 1000 raw or unprocessed food products. The data in FooDB was collected from many sources including textbooks, scientific journals, on-line food composition or nutrient databases, flavour and aroma databases and various on-line metabolomic databases. This literature-derived information has been combined with experimentally derived data measured on thousands of compounds from more than 40 very common food products through the Alberta Food Metabolome Project which is led by David S. Wishart. Users are able to browse through the FooDB data by food source, name, descriptors or function. Chemical structures and molecular weights for compounds in FooDB may be searched via a specialized chemical structure search utility. Users are able to view the content of FooDB using two different “Viewing” options: FoodView, which lists foods by their chemical compounds, or ChemView, which lists chemicals by their food sources. Knowledge about the precise chemical composition of foods can be used to guide public health policies, assist food companies with improved food labelling, help dieticians prepare better dietary plans, support nutraceutical companies with their submissions of health claims and guide consumer choices with regard to food purchases.
METAGENassist is a freely available web server for comparative metagenomic analysis. Comparative metagenomic studies involve the large-scale comparison of genomic or taxonomic census data from bacterial samples across different environments. Historically this has required a sound knowledge of statistics, computer programming, genetics and microbiology. As a result, only a small number of researchers are routinely able to perform comparative metagenomic studies. To circumvent these limitations, METAGENassist was developed to allow metagenomic analyses to be performed by non-specialists, easily and intuitively over the web. METAGENassist is particularly notable for its rich graphical output and its extensive database of bacterial phenotypic information.
David S. Wishart is a Canadian researcher and a Distinguished University Professor in the Department of Biological Sciences and the Department of Computing Science at the University of Alberta. Wishart also holds cross appointments in the Faculty of Pharmacy and Pharmaceutical Sciences and the Department of Laboratory Medicine and Pathology in the Faculty of Medicine and Dentistry. Additionally, Wishart holds a joint appointment in metabolomics at the Pacific Northwest National Laboratory in Richland, Washington. Wishart is well known for his pioneering contributions to the fields of protein NMR spectroscopy, bioinformatics, cheminformatics and metabolomics. In 2011, Wishart founded the Metabolomics Innovation Centre (TMIC), which is Canada's national metabolomics laboratory.
