Yamamoto S et al. (2011), INOH: ontology-based highly structured database...

XB-ART-44500

Database (Oxford) 2011 May 17;2011:bar052. doi: 10.1093/database/bar052.

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INOH: ontology-based highly structured database of signal transduction pathways.

Yamamoto S , Sakai N , Nakamura H , Fukagawa H , Fukuda K , Takagi T .

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The Integrating Network Objects with Hierarchies (INOH) database is a highly structured, manually curated database of signal transduction pathways including Mammalia, Xenopus laevis, Drosophila melanogaster, Caenorhabditis elegans and canonical. Since most pathway knowledge resides in scientific articles, the database focuses on curating and encoding textual knowledge into a machine-processable form. We use a hierarchical pathway representation model with a compound graph, and every pathway component in the INOH database is annotated by a set of uniquely developed ontologies. Finally, we developed the Similarity Search using the combination of a compound graph and hierarchical ontologies. The INOH database is to be a good resource for many users who want to analyze a large protein network. INOH ontologies and 73 signal transduction and 29 metabolic pathway diagrams (including over 6155 interactions and 3395 protein entities) are freely available in INOH XML and BioPAX formats. Database URL: http://www.inoh.org/

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Species referenced: Xenopus laevis
Genes referenced: bmp2 lif lrp5 smad1

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	Figure 1. INOH data model. Boxes represent class objects (nodes and edges) and their attribute(s), and arrows show inheritance relationships. Multiple values are allowed at underlined attributes. Asterisks indicate that the value for the attribute is filled from INOH ontology terms.
	Figure 2. INOH pathway. Each blue window represents event of different granularity, and green window represents molecular complex. Light blue hexagons are Process nodes that show molecular interactions, and green hexagon is EventRelation node that shows positive/negative indirect relation between events.
	Figure 3. Screenshot of Ontology Viewer. (A) Example of search result. (B) Attribute and ontology hierarchy view. (C) Example of INOH pathway data accessed through INOH Ontology Viewer.
	Figure 4. Screenshot of INOH Client. Window consists of five areas; tool panel (Objects and Properties panels), diagram editing area, over view area, magnified view area and external DB links area. User can search and download pathways, and pathways can be then modified and saved. When switching from normal view to reduced view in toolbar, picture focusing on molecular transition is displayed in diagram editing area.
	Figure 5. Previous/following event search. BMP2 signaling does ‘cross-talk’ with Wnt and LIF signaling. (A) Search following events of ‘Nuclear import of Smad1:Smad4’ in BMP2 signaling. The curated following events are connected to the event by the PASSING edges. (B) List of following events and its diagram. (C) Wnt and LIF signaling is pasted on same canvas. The inferred following events are connected by the PseudoPASSING edges.
	Figure 6. Homologous search in Wnt signaling. (A) Search homologous events of ‘Binding of Wnt, Frizzled and Arrow/LRP5/6 (Canonical)’ in Wnt signaling. (B) List of homologous events and its diagrams. (C) Homologous events in C.elegans, D.melanogaster, X.laevis and Mammalia can be pasted on same canvas for comparison.
	Figure 7. Similarity Search of FGF signaling (C.elegans). (A) The ligand-receptor binding in FGF signaling (C.elegans). (B) Result screen of similarity search. (C) The hierarchical tree of ‘FGF’ molecule in MoleculeRole ontology and some signaling pathways similar to FGF signaling (C.elegans). Green/orange edges represent correspondence relation to MoleculeRole ontology.
	Figure 8. Similarity Search on all INOH pathways using large protein–protein network query. (A) Protein–protein network related to acute allergic diseases displayed in Cytoscape. (B) Results of similarity search on INOH pathways using network as query. (C) Example of INOH pathways that have similar molecules and interactions in protein–protein network dataset. Similar molecules and interactions are highlighted with same colors in (A) and (C). These results can be found here. http://www.inoh.org/similarity-search/project.php?session=1πd=526.

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Ashburner, Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. 2000, Pubmed