Pathway Commons at Virtual Cell: Use of Pathway Data For Mathematical Modeling

Abstract

Mathematical models of biological systems are rapidly proliferating and many are now publicly available. However, their distribution and sharing is limited because in the absence of extensive accompanying documentation, there is a significant barrier for understanding and reuse. The Virtual Cell (VCell) is a modeling and simulation framework designed for building of a wide range of mathematical models; more than 3,000 users created more than 29,000 models, of which more than 500 were made public in the VCell database. There is a strong need for methods and tools that enable users to easily create well-annotated models. On the other hand, a large number of public databases provide huge collections of well-annotated physical entities and molecular interactions. Most provide data in RDF-based ontology formats (such as BioPAX) which typically cannot be converted to XML-based modeling formats without loss of information. To resolve this issue, we introduced two new concepts (encoded in VCML), a Pathway Model and a Relationship Model, which allow unambiguous storing of data extracted from pathway databases and the mapping of pathway elements to model entities. We used this technology to implement a new interface that makes available the Pathway Commons collection of databases as a resource that every VCell modeler will have at his/her disposal. Using a customized query interface, one can search pathway databases from inside VCell, import and store the entries of interest alongside a mathematical model, and create a new model based on the pathway data or link existing elements of the model to pathway data entities. This capability can help researchers to make annotated models that are easier to share with the community, as well as quickly create first iterations of a quantitative model from a wealth of well-annotated biological data.