Integration of the Gene Ontology into an object-oriented architecture

Abstract

Background: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model.

Results: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, "transforming growth factor-beta (TGF-beta) receptor complex assembly" (GO:0007181).

Conclusion: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.

Figure 1

The GO terms associated with the process, TGF-beta receptor complex assembly (GO: GO:0007181). Lines with solid diamonds () at the end indicate composition. These are read from the diamond end, for example, as 'cell' (GO:0005623) contains a 'membrane' (GO:0016020). Lines with open triangles () represent generalizations. These are read from the triangle end, as a 'membrane' (GO:0016020) is a general type of 'plasma membrane' (GO:0005886). A) Directed acyclic graph for the cellular component GO terms associated with TGF-beta receptor complex assembly (GO:0007181). B) Object-oriented representation of the DAG described in Figure 1A (white). Additional cellular components not represented by the current Gene Ontology, but essential to the TGF-beta receptor complex assembly process are shown in the gray boxes (i.e. TGF-beta, TGF-beta receptors, SMAD2)

Figure 2

An example of the sequence diagram showing the TGF-beta receptor complex assembly (GO:0007181). The binding of TGF-beta to its receptor (GO:0050431), receptor heterotetramerization (RI and RII homodimers, heterodimerizing)(GO:0046982), translation (GO:0043037), transferase activity (GO:0016740), and Smad 2 binding (GO:0046332) and activation (GO:0042301) are shown.

Figure 3

An example of an activity diagram showing the main and alternative flow of events occurring during TGF-beta receptor complex assembly (GO:0007181).

Figure 4

An example of a class diagram showing the interactions between the components of the TGF-beta receptor complex (GO:0007181) (grayed). Cellular components containing these gene products are also shown. Due to space constraints functions are named using their corresponding GO ids. The class diagram was also constructed with a descriptive function name [see Additional file 8]. The GOid reference list is: GO:0042803, protein homodimerization activity; GO:0005160, TGF beta receptor binding; GO:0046982, protein heterodimerization activity, GO:0050431, TGF beta binding, GO:0005524, ATP binding; GO:0016740, transferase activity, GO:0046332, Smad binding; GO:0042301, phosphate binding; GO:0003677, DNA binding.