By Gary Bader, Assistant Professor, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto.

Imagine you are confronted one day by a pile of hundreds of tiny metal gears, springs, screws and such. Could you tell by looking at that pile that you could assemble a Swiss watch from it? Now imagine that you are given a list of parts for a person and want to know how an estimated 25-100 trillion cells in the human body function over a lifetime.

The types of things that are in the human parts list include biomolecules like DNA, RNA, proteins and other molecules (such as vitamins, fats and sugars). We are at this stage right now in biology. The human genome project has provided us with a large number of parts, but we don’t know they fit together, how the biomolecules interact. Finding and understanding this information is important, as biomolecules interact inside us and arrange themselves into intricate networks and pathways that control all aspects of a cell’s function. Diseases arise if this network is broken in some specific way. 

A major challenge for studying the cellular network is collecting all known public information from very diverse sources, such as the biomedical literature, raw experimental data and the hundreds of existing pathway databases. Open access content and open source software systems are critical for overcoming this challenge. Once information is freely shared in open, standard formats, it can be aggregated, integrated, searched, visualized and analyzed. The Bader lab is involved in a number of open access projects that together work towards this goal.

Analysis and Visualization

Cytoscape (see screen-shot below) is a bioinformatics software platform for visualizing molecular interaction networks and integrating these interactions with gene expression profiles and other state data. Additional features are available as plugins. Plugins are available for network and molecular profiling analyses, new layouts, additional file format support and connection with databases. Plugins may be developed using the Cytoscape open Java software architecture by anyone and plugin community development is encouraged. Cytoscape was originally developed at the Institute of Systems Biology and is now a collaborative effort involving many different academic and commercial groups. Cytoscape is freely available under the LGPL open source license for academic and commercial use.

Database Software

cPath is an open source database and web application for collecting, storing, browsing and querying biological pathway data. cPath makes it easy to aggregate custom pathway data sets available in standard exchange formats from multiple databases, present pathway data to biologists via a customizable web interface, and easily export pathway data via a web service to third-party software for visualization and analysis. cPath is software only, and does not include new pathway information. This work is done in collaboration with the Sander group of the Computational Biology Center at Memorial Sloan-Kettering Cancer Center in New York City. The cPath software is freely available under the LGPL open source license for academic and commercial use.

Demo's are available at the cPath project website for protein-protein interactions and pathways.

Pathway Content

The Cancer Cell Map contains selected cancer related signaling pathways which you can browse or search. Biologists can browse and search the Cancer Cell Map pathways. View gene expression data on any pathway. Computational biologists can download all pathways in the standard BioPAX format for global analysis. Software developers can build software on top of the Cancer Cell Map using the web service API or download and install the cPath software to create a local mirror. This work is done in collaboration with the Sander group of the Computational Biology Center at Memorial Sloan-Kettering Cancer Center in New York City. All content is made freely available under a Creative Commons license.

Pathway Commons will be a convenient point of access to biological pathway information collected from public pathway databases, which you can browse or search. Pathways include biochemical reactions, complex assembly, transport and catalysis events, and physical interactions involving proteins, DNA, RNA, small molecules and complexes. This work is done in collaboration with the Sander group of the Computational Biology Center at Memorial Sloan-Kettering Cancer Center in New York City.

Pathway Data Exchange Standards

BioPAX (Biological Pathway Exchange) is a collaborative effort to create an OWL XML data exchange format for biological pathway data. BioPAX covers metabolic pathways, molecular interactions and protein post-translational modifications. Future versions will expand support for signaling pathways, gene regulatory networks and genetic interactions. PSI-MI (The Proteomics Standards Initiative Molecular Interactions) XML Schema format allows exchange of molecular interaction data, focusing on protein-protein interactions. Both of these projects are large international collaborative efforts involving many different academic and commercial groups. The formats are open under the LGPL license and documentation is open under the Creative Commons license.

The open source Cytoscape software displaying a protein interaction network from baker's yeast (Saccharomyces cerevisiae). Yeast is an important model organism that has been used to study many aspects of cell function which are also relevant to human cells and disease.