Meta-All: a system for managing metabolic pathway information

Abstract

Background: Many attempts are being made to understand biological subjects at a systems level. A major resource for these approaches are biological databases, storing manifold information about DNA, RNA and protein sequences including their functional and structural motifs, molecular markers, mRNA expression levels, metabolite concentrations, protein-protein interactions, phenotypic traits or taxonomic relationships. The use of these databases is often hampered by the fact that they are designed for special application areas and thus lack universality. Databases on metabolic pathways, which provide an increasingly important foundation for many analyses of biochemical processes at a systems level, are no exception from the rule. Data stored in central databases such as KEGG, BRENDA or SABIO-RK is often limited to read-only access. If experimentalists want to store their own data, possibly still under investigation, there are two possibilities. They can either develop their own information system for managing that own data, which is very time-consuming and costly, or they can try to store their data in existing systems, which is often restricted. Hence, an out-of-the-box information system for managing metabolic pathway data is needed.

Results: We have designed META-ALL, an information system that allows the management of metabolic pathways, including reaction kinetics, detailed locations, environmental factors and taxonomic information. Data can be stored together with quality tags and in different parallel versions. META-ALL uses Oracle DBMS and Oracle Application Express. We provide the META-ALL information system for download and use. In this paper, we describe the database structure and give information about the tools for submitting and accessing the data. As a first application of META-ALL, we show how the information contained in a detailed kinetic model can be stored and accessed.

Conclusion: META-ALL is a system for managing information about metabolic pathways. It facilitates the handling of pathway-related data and is designed to help biochemists and molecular biologists in their daily research. It is available on the Web at http://bic-gh.de/meta-all and can be downloaded free of charge and installed locally.

Figure 1

Simplified schema of the Meta-All database. Simplified UML [30] structure diagram of the database schema. The complete schema is available at the META-ALL project Web page. Rectangles symbolise classes (e.g. substance) without attributes and methods. Lines between classes symbolise relationships between the classes, called associations. Small diamonds at one of the ends of a line symbolise part-of relations. A black diamond means a composition (the single parts cannot exist on their own), an open diamond means an aggregation (the single part can exist on its own). A line with a triangle at one of the ends symbolises an inheritance relation (e.g. both metabolite class and enzyme class belong to the substance class). Numbers next to lines specify the allowed cardinalities for an instance of that class, for example, the 1..* at the line between metabolite and macromolecule means that a macromolecule consists of at least one (1) metabolite up to an unlimited (*) number of metabolites.

Figure 2

Screenshot of the Meta-All Web-Interface. The Web-Interface is divided into several parts, which correspond with the main parts of the database schema as described in Fig. 1. There are tabs for substances, locations, conversions, pathways and the management of versions and publications. These tabs open sub-pages each with several items belonging to the particular part of the schema. a) shows an input form for inserting data about metabolites, and b) is a simple report listing enzymes. c) is showing taxonomy information of the organisms stored in the demo instance of META-ALL, and d) shows a step from a wizard for browsing top-down through a pathway. On the left side, there is a select list for choosing one of the substances listed in the report on the right side. These substances belong to a conversion selected in the previous step. By clicking on the "next"-button, details of the chosen substance will be shown.

Figure 3

Data from Meta-All visualised in Vanted. Visualisation of the sucrose breakdown pathway in the potato tuber [12]. The pathway data stored in META-ALL was exported into an SBML file using the SBML export filter. The file was subsequently loaded into the network visualisation system VANTED [22]. As the SBML format does not specify a layout of the model, an automatic force directed layout was applied which served as a starting point for the manual refinement of the overall model layout.