New possibilities 1. EBI data pack – database modules for main databases supported by EBI: Ensembl, UniProt, ChEBI,Reactome, IntAct, GO, BioModels, SBO. These databases are installed on the special BioUML server and can be easily searched and used by BioUML workbench (client). 2. Composite database module – allows a user to specify a set of databases that he would like to use simultaneously as a source of components during creation and editing of diagrams. 3. Composite diagrams (hierarchical) – allow a user to join several existing diagrams/models into a bigger one. 4. Experiment – allows to specify conditions (initial values, parameters, external stimulus, etc.) for virtual experiments on the diagram. 5. BioHub – an approach that allows to arrange relationships between biological objects from different databases formally and use this information for searching. Results of such search can be presented as an editable graph. 6. Graphic notation editor – it allows an advanced user to create new graphic notation or extend an existing one. As an example SBGN graphic notation was created. 7. Microarray data analysis - allows a user to load his microarray data, identify up/down regulated genes and highligt diagram elements according to microarray data or results of this data analysis. BioUML – new concepts and possibilities Nikita Tolstykh, Sergey Lapukhov, Ilya Kiselev, Aleksey Shadrin and Fedor Kolpakov Institute of Systems Biology, Novosibirsk, Russia; Design Technological Institute of Digital Techniques SB RAS, Novosibirsk, Russia *Contacts: Metaphor Biological systems reconstruction is like solitaire (patience) game: desk – BioUML editor; solitaire – biological pathway; cards – biological objects (genes, proteins, lipids, etc.); pack of cards– different biological databases. Levels of biological information BioHub concept BioHUB – an approach link information from different databases. Main usage: binding microarray (omics) data to pathway diagrams; graph search; DBReferences editor; microarray (omics) data analysis. BioHUB is conceptually similar with MIRIAM standard and defines: references to database objects; relationships between biological objects (for example: is-a, part-of, form-of ). Each bar corresponds to one value from corresponding microarray series. BioHub usage: graph search engine Graphic notation editor Motivation Reconstruction of complex biological systems requires integrated software that provides: 1. integration with a wide range of biological databases; 2. integration with omics data; 3. powerful search capabilities; 4. visual modelling approach; 5. client-server architecture for team work. Main ideas for data integration and pathway reconstruction: - escape information duplication. - classify components of biological pathways by levels. - each next level should refer but do not duplicate information from previous levels. - use free EBI databases whenever it is possible. BioHub usage: coloring diagrams according to microarray data BioUMLworkbench BioUML ( is an open source integrated Java workbench for systems biology. Its core is a meta-model that provides an abstract layer for comprehensive formal description of wide range of biological and other complex systems as a compartmentalized graph. Connection types: 1) directed – input  output. Transformation function can be used; 2) undirected – contact. Indicates that 2 nodes in mode is the same entity. Semantic constraints: There are semantic constraints, for example: block can have only one input for each variable. Two inputs are forbidden for the same variable. Flat model: Before Matlab or Java code generation composite model is transformed into flat model and usual genertions routines are used. Composite diagram (hierarchical) : main concepts Block types: 1) block – only mathematical equations. Used mainly for physiological models; 2) subdiagram – other diagram Virtual experiment concept To make a virtual experiment it is frequently needed to modify initial model. To skip model duplications for each virtual experiment we introduce “changes” concept. Typical modifications (changes) are: changing of initial values changing of model parameters to imitate different conditions or mutations deleting of some model elements to imitate knock-out mutations adding events to imitate external influences on the model. The figure below demonstrates how changes are shown on diagram for pRB knock-out experiment. Conclusion We believe that new version of BioUML workbench will greatly simplify, speed up and improve the process of formal description and reconstruction of biological pathways. Acknowledgements This work was supported by FP6 grant “Net2Drug”, FP7 grant "LipidomicNet" and interdisciplinary project 46 of SB RAS.