WP11 - Enhancing enzyme and enzyme-ligand data
In the current projects the BRENDA database will be enhanced for the area of systems biology. This includes the development of new, context specific methods for the text-mining based addition of information to BRENDA especially in the fields of kinetic data and enzyme/disease relationships. In addition new data submission and data export options will be implemented that should allow the direct integration of BRENDA data into metabolic network models and network simulation programs. New information fields necessary for systems biology approaches will be implemented. Finally the visualisation of enzyme data will be strongly improved, in particular the visualisation of function-related features like information on the active centre or other structural information like glycosylation sites, membrane anchors, etc. will be mapped on a display of the enzyme 3D structure. The – meanwhile highly used – BRENDA tissue ontology will be enhanced and new enzyme classes will be identified.
Task 1: Development of text-mining for kinetic data and disease
We will develop and implement methods that extract numerical, kinetic data like KM-values, Turnover numbers, inhibition constants etc. from abstracts, and – as far as available – from the body of the article. Another field of high importance is the relationship between enzyme function or malfunction and diseases. We will develop and implement a method that combines the OMIM information with literature text-mining approaches to get a rather complete picture. Our approach will be based by a method published by us in 2005. This methods will be further developed to be able to analyse the text in more detail and to allow frequent updates of its contents and will be functional and running in month 36 (D11.01)
Task 2: Development of methods for systems biology
In the past and still to a large extent presently most of the BRENDA is – after the appropriate query and filtering – read and utilized by humans for their research. In the last years researchers in the field of systems biology build large-scale models of regulatory and metabolic networks for analysis and simulation and use many of the enzyme data from BRENDA in their models. We will amplify the currently available web-service simplify its application and create a web service in SBML format (Systems Biology Markup Language as an export options that can directly be imported into simulation programs for metabolic pathways. This service will be made available in month 12 (D11.02)
We will also include additional information fields like IC50, with high importance to the pharmaceutical industry, into the information fields routinely covered by BRENDA. This requires a change in the annotation process and also in the query routines. The 2D-structures of these inhibitors will be linked to the ChEBI ontology (WP12) (These data will be online in month 36 (D11.03))
Task 3: Further Development of the BRENDA tissue ontology (BTO)
The BRENDA tissue ontology available in OBO, has become a standard in the field and is used by many researchers beyond the enzyme-related field. The ontology will be expanded, branches and nodes will be added to the tree, new terms including their definitions will be compiled and references supporting these facts will be added.
In the context of SLING this will be done in connection and supporting PRIDE, the PRoteomics IDEntifications database. The expanded ontology will be online in month 36 (D11.04)
Task 4: Visualisation of enzyme functional and structural data on 3D-structures
With the increasing number of available 3D structures for enzymes the sequence-based information of active centres, sites for post-translational modification, targeting and pro-sequences, anchoring, etc. can be mapped to the 3D structure and visualised by the user. The software for this new option will be developed in the context of SLING and will make use of the protein features annotated by the UNIPROT project at the EBI and the SIB. This feature will be available in month 30 (D11.05)
Task 5: Identification of new enzyme classes
In cooperation with the SIB and the EBI new enzyme classes will be identified from literature. After the assignment of new or preliminary EC numbers (latter resulting from FELICS collaborative activities), the corresponding BRENDA entries with enzyme-functional data will be annotated accordingly. The newly classified enzyme classes (~40 items) will be proposed to the Enzyme Commission of the IUBMB for inclusion into the EC-system (month 36 D11.06)
The project envisages attendance at two conferences to promote the work, one of them outside Europe. It also envisages one visit to each of SIB and the EBI by TUBS staff, two visits from EBI to TUBS, and one from SIB to TUBS.