The Cell Cycle Ontology: an application ontology for the representation and integrated analysis of the cell cycle process

Abstract

The Cell Cycle Ontology (http://www.CellCycleOntology.org) is an application ontology that automatically captures and integrates detailed knowledge on the cell cycle process. Cell Cycle Ontology is enabled by semantic web technologies, and is accessible via the web for browsing, visualizing, advanced querying, and computational reasoning. Cell Cycle Ontology facilitates a detailed analysis of cell cycle-related molecular network components. Through querying and automated reasoning, it may provide new hypotheses to help steer a systems biology approach to biological network building.

Figure 1

Example of the local neighborhood of the protein SWI4_YEAST: some of the types of relationships used within CCO depict how a given protein (SWI4_YEAST) is connected to the organism it belongs to (S. cerevisiae), its coding gene (SWI4_yeast), biological processes (G1/S transition of mitotic cell cycle), cellular localization (nucleus), interactions (physical interactions), protein transformations (post-translational modifications), and its orthology group.

Figure 2

Simple RDF triple sample showing the subject (Nucleus), the predicate (part_of) and the object (Cell).

Figure 3

RDF matching model: while querying an RDF model, a matching process is performed against the graph model. In the sample, the triples '?protein is_a CCO_B0000000' and '?protein rdfs:label ?protein label' are matched against the graph on the left.

Figure 4

OWL property (part_of) sample: the property 'part of' links individuals belonging to a class (for example, 'Nucleus') to individuals of the class 'Cell'. A restriction of the type 'some part_of Cell' on the class 'Nucleus' defines an anonymous class (dotted shape), and will imply that individuals belonging to the class 'Nucleus' also belong to (are 'part_of') the class 'Cell'.

Figure 5

CCO visualization applet. The CCO terms are shown as clickable, color-coded nodes, and mouse actions of the user are translated into pre-defined SPARQL queries that operate on the RDF representation of CCO. The results are returned as an XML file, which is translated into new nodes and edges that are then shown in the display. This visualization sample shows the local neighborhood of the protein WEE1_SCHPO ('Mitosis inhibitor protein kinase wee1').

Figure 6

CCO pipeline. The CCO data integration pipeline scheme plots the principal phases: set-up, data integration and system's life cycle. In the 'set-up' phase, several existing ontologies are integrated and merged: the Gene Ontology, the Relations Ontology, the Molecular Interactions ontology, an upper level ontology (see 'An upper level ontology for application ontologies in the life sciences' section) and an ontology holding taxonomical terms for the four model organisms supported by CCO (A. thaliana, H. sapiens, S. cerevisiae and S. pombe). A core cell cycle ontology is generated as output from this set-up phase, which in turn serves as input for the 'data integration phase' where GOA annotations and protein data, such as protein-protein interactions, are integrated. Finally, 'life cycle' phase depicts the maintenance of the system by considering the stages of updating the integrated data (such as ontologies, protein data). This phase also shows the generation (export) in different formats for further exploitation.

Figure 7

Upper level ontology for CCO. The ULO provides a hierarchical scaffold, including generic terms (for example, cell cycle gene), which serve as 'hooks' for hanging the integrated resources. The dashed rectangles represent the type of data residing below the parental nodes: the node called 'Data from GO' under the term 'cellular component' shows the placeholder where the cellular components from GO are placed (for example, nucleus), the node 'Data from UniProt' under the term 'protein' shows the placeholder where protein data from UniProt resides (for example, p53), and so forth.