Major Pathway Databases Pathway databases are being created all around the world. On a periodical basis, we download and parse those text documents, extract and transform the information into our format, and insert the data into our relational database. Next, we compare features of PathCase with KEGG, BioCyc and Reactome as follows: Browsing: in the KEGG website, metabolic pathway pages are separated from pathway browsing interfaces. SIB - Swiss Institute of Bioinformatics; CPR - Novo Nordisk Foundation Center Protein Research; EMBL - European Molecular Biology Laboratory All graph manipulations such as zooming in and out, panning and application of different layouts are carried out on the client side with no server side requests, which makes PathCase highly scalable. A pathway p is deficient in an annotation c, if c is significant in p (i.e. The pathway viewer is available when viewing pathway or process details, as well as when viewing the results of one of PathCase built-in queries. Furthermore, we say that c annotates p with the enrichment ratio R(c, p, S)=k(c, p)/ [n(p)*K(c, S)/N(S)]. JavaScript and AJAX technologies are used for a rich, dynamic user experience. Various data exchange standards have been developed to assist the storage, organization, and exchange of pathway information. Right-click menu directs PathCase interface to a query page with automatically filled fields with respect to the entity being queried from the graph viewer. The database is a high-quality database focused on metabolic pathways originally formed by SRI International’s bioinformatics research group. The next layer is the data object library, which provides a programmer-friendly interface to the system content stored in the databases that allows for data to be accessed, created and updated. Results: In this article, we present the new features of PathCase, a system to store, query, visualize and analyze metabolic pathways at different levels of genetic, molecular, biochemical and organismal detail. Organism viewer is treated as the primary control point of organisms synchronized with the pathway visualization, and gene viewer. Also, processes related to genes can be highlighted by either selecting a gene from the gene viewer, or selecting all genes of a chromosome by selecting a chromosome. The workshop focuses on the principles and concepts required for analyzing and conducting pathway and network analysis on a gene list from any organism, although focus will be on human and model eukaryotic organisms. (GO Concept Enrichment/Deficiency):For a given GO concept c, assume K(c, S) out of N(S) processes in S are annotated by c. And, for a given pathway p with n processes, let k(c, p) be the number of processes annotated by c in p. We say that c enriches p if its annotation is significant in p, and the observed annotation count k(c, p) of c in p is greater than the expected annotation count n(p)*[K(c, S)/N (S)] of c in p, which is k(c,p) > n(p)*[K(c, S)/N(S)]. In terms of item (5), we are extending PathCase with systems biology models, and metabolomics analysis. Pathway bioinformatics is a subfield of bioinformatics that is concerned with pathway algorithms, ontologies, visualizations, and databases [4]. This keeps our database up-to-date as KEGG pathways data are modified. A big welcome to “Bioinformatics: Introduction and Methods” from Peking University! The first one, advanced querying interface (AQI), is a graphical query language (Mayes, 2007), and allows for custom queries for (i) pathways, processes, molecular entities and organisms, (ii) metabolic network neighborhoods, or pathway network neighborhoods and (iii) metabolic network paths or pathway network paths. It is also possible to export visualizations of these databases to external applications (i.e. The databases vary greatly in their content, quality, and completeness. In terms of item (4), currently, PathCase runs on three different datasets: PathCase with (i) KEGG pathways (Kanehisa et al., 2006), (ii) sample pathways from the literature (Michal, 1999) and (iii) BioCyc pathways for humans. Metabolic Pathways. We have also tested and verified the suitability of Reactome metabolic pathways for PathCase. Some molecules like H2O, H2O2, NH3, O2, are present in most reactions and, hence, occupy a large part of the visualization. GraphViewer retrieves raw pathway information (as an XML document from the web services) including genes and organism taxonomy of a pathway, and translates it into an easy-to-understand graph visualization detailing the interconnections between pathways, processes and molecular entities at the client side. (GO Annotation Significance): Given a pathway set S, an annotation concept c and a pathway p in S, c is significant in p if the statistical significance of c in p is less than the threshold γ, namely, P(c, p, S) < γ. Queries can also be invoked from the Pathway Viewer. (a–b) Gene viewer listing chromosomes of a selected organism (a and b). WikiPathways WikiPathways is a community resource for contributing and maintaining content dedicated to biological pathways. This Course Video Transcript. Section 4 is a summary of the querying capabilities of PathCase. In addition, this component provides an additional panel called minimap that views a sketch of the graph at once, and allows user to quickly move to a particular position. Contents of these data sources are put together, maintained and curated by large numbers of biologists. MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Since the last publication on PathCase (Krishnamurthy et al., 2003), two fundamental developments have taken place. Today, metabolic pathways are stored in knowledge bases that can be queried, modified, copied, and extended with ease, precision, and speed. VisANT for KEGG and CytoScape for Reactome/BioCyc) for dynamic visualization and graph theoretical analysis of pathways (e.g. The software has been licensed by more than 10,000 groups and powers multiple pathway/genome database websites. 3 IMPACT The Database for Annotation, Visualization and Integrated Discovery (DAVID ) v6.8 comprises a full Knowledgebase update to the sixth version of our original web-accessible programs. MetNetAccess has been used to curate many pathways for different organisms in MetNetDB (Wurtele et al., 2007). Nucleic Acids Res 44: 471-480. 46. Pathways play a key role in advanced studies of genomics. A group of annotation sources collecting similar biological questions, such as: "Pathways" is an annotation category consisting of BioCarta, KEGG, etc. In addition, PathCase system allows saving pathways in BioPAX-formatted files. Modeling: In PathCase, pathways are represented as hypergraphs (Berge, 1973) where nodes are molecular entities participating in a reaction as substrates or products, and edges are enzymes which catalyze reactions. Any registered WikiPathways user can contribute, and anybody can become a registered user. built-in queries, AQI) in PathCase. degree distributions, shortest paths). generated at query execution time) client-side pathway visualization tool with (i) an integrated pathway viewer, gene viewer (to display locations of a set of genes that play a role in a pathway), organism viewer (allowing users to choose from organism groups) and ontology viewer, and (ii) a variety of automated and flexible capabilities for layout generation, manual layout editing and layout saving. Another tool takes any user-provided set of genes, and retrieves a set of pathways that are tightly associated with the input genes. Our approach is to model each pathway as a network of GO-based enzyme functions, which we call the (pathway) GO functionality template (PFT) (Cakmak et al., 2007). Limitations of biological databases Though crucial for data organization and storage, the challenges affiliatedwith biological databases are manifold. BioMiner (Sirava et al., 2002) is a software library developed for modeling and visualizing biochemical data. Contribute to BRENDA! For the drawing of PFT graphs, the open-source QuickGraph library (QuickGraph) is used. The workshop focuses on the principles and concepts required for analyzing and conducting pathway and network analysis on a gene list from any organism, although focus will be on human and model eukaryotic organisms. Java is chosen for powerful and highly responsive dynamic graph drawings. More generally, an entire pathways database can be viewed as a single large graph of interconnected reactions, in which certain subgraphs are identified as specific pathways. Sharing: PathCase provides three distinct mechanisms to share its data and visualizations with the scientific community: (i) all pathways can be exported to BioPAX-formatted documents (BioPAX, 2004), (ii) visualizations can be saved in an image format (JPEG) and (iii) PathCase web service methods can be directly accessed in order to query the PathCase database and obtain the results in XML format. REACTOME is an open-source, open access, manually curated and peer-reviewed pathway database. The highest 10 ranking pathways per method are shown for Webgestalt ZZBioCarta[[ and PANTHER. 3b). Starting with the server side, the first layer consists of the databases, which contain the actual pathways information and allow for efficient querying. In comparison, KEGG, BioCyc and Reactome provide a bird's-eye view of all pathways in a compact view; when an individual pathway is selected from the bird's-eye view, the pathway is displayed alone, isolated from the rest of the bird's-eye visualization. The second set contains the KEGG metabolic pathways (Kanehisa et al., 2006), licensed from KEGG. These meta-data databases are especially suited for analysing consolidated pathway information. In addition, there are a small number of entries created by curators. Each database strongly reflects its builder’s intent and purpose. ‘Find processes that are at most N steps from a given process’), path queries (e.g. For instance, we relocate all regulator and cofactors to fixed positions around process entities, whereas automated layout algorithms would position them arbitrarily to reduce edge and node overlaps. The SQL Server software was donated by Microsoft. PATIKAWeb employs a semi-dynamic system for displaying pathways. Pathways can be visualized at different detail levels, such as the expanded form, which displays all the components of a pathway (from reactions to activators) and the collapsed form, which is used to visualize the connections between pathways in a compact way.