Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks (original) (raw)

1. Paul Shannon1,
2. Andrew Markiel1,
3. Owen Ozier2,
4. Nitin S. Baliga1,
5. Jonathan T. Wang2,
6. Daniel Ramage2,
7. Nada Amin2,
8. Benno Schwikowski1,5, and
9. Trey Ideker2,3,4,5
10. 1 Institute for Systems Biology, Seattle, Washington 98103, USA
11. 2 Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
12. 3 Department of Bioengineering, University of California-San Diego, La Jolla, California 92093, USA

Abstract

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.

Footnotes

• Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.1239303.

• [The Cytoscape v1.1 Core runs on all major operating systems and is freely available for download from http://www.cytoscape.org/ as an open source Java application.]

• ↵6 Biological semantics vary widely within the biological community as well as fromproject to project. If biological semantics were in the Cytoscape Core, we would be faced with a difficult question; which semantics should we use? Cytoscape avoids this problem by leaving it to plug-in writers to adopt semantics adequate to the problem at hand. Of course, there is often substantial biological significance associated with data in the Core. For example, the core may represent a node (an abstract concept free of biological semantics) whose label is GCN4 (a text string with significance to yeast biologists as an important transcription factor) or we might use the Core to define node attributes entitled “expression ratio” or “cellular compartment.” In this way, great freedom and flexibility—the ability to accommodate new biological problems—is gained by not inscribing the notion of specific biological entities directly into the semantics of Cytoscape's Core.

• ↵7 Although attribute-based layout was initially implemented as a plug-in, its general applicability and tight integration with several of Cytoscape's core features (graph layout and node attribute mapping) ultimately led us to incorporate it into the Cytoscape Core platform. Thus, plug-ins also provide a general means of introducing and testing new features.

• ↵5 Corresponding authors. E-MAIL trey{at}bioeng.ucsd.edu; FAX (858) 534-5722. E-MAIL benno{at}systemsbiology.org; FAX (206) 732-1299

• ↵4 Present address: University of California, San Diego, Department of Bioengineering, La Jolla, California 92093, USA.

• • Accepted August 22, 2003.
  • Received February 1, 2003.

• Cold Spring Harbor Laboratory Press

•