We present an algorithm for the layout of undirected compound graphs, relaxing restrictions of previously known algorithms in regards to topology and geometry. The algorithm is based on the traditional force-directed layout scheme with extensions to handle multi-level nesting, edges between nodes of arbitrary nesting levels, varying node sizes, and other possible application-specific constraints. Experimental results show that the execution time and quality of the produced drawings with respect to commonly accepted layout criteria are quite satisfactory. The algorithm has also been successfully implemented as part of a pathway integration and analysis toolkit named PATIKA, for drawing complicated biological pathways with compartmental constraints and arbitrary nesting relations to represent molecular complexes and various types of pathway abstractions. © 2008 Elsevier Inc. All rights reserved

BackgroundGraph-based pathway ontologies and databases are widely used to represent data about cellular processes. This representation makes it possible to programmatically integrate cellular networks and to investigate them using the well-understood concepts of graph theory in order to predict their structural and dynamic properties. An extension of this graph representation, namely hierarchically structured or compound graphs, in which a member of a biological network may recursively contain a sub-network of a somehow logically similar group of biological objects, provides many additional benefits for analysis of biological pathways, including reduction of complexity by decomposition into distinct components or modules. In this regard, it is essential to effectively query such integrated large compound networks to extract the sub-networks of interest with the help of efficient algorithms and software tools.ResultsTowards this goal, we developed a querying framework, along with a number of graph-theoretic algorithms from simple neighborhood queries to shortest paths to feedback loops, that is applicable to all sorts of graph-based pathway databases, from PPIs (protein-protein interactions) to metabolic and signaling pathways. The framework is unique in that it can account for compound or nested structures and ubiquitous entities present in the pathway data. In addition, the queries may be related to each other through "AND" and "OR" operators, and can be recursively organized into a tree, in which the result of one query might be a source and/or target for another, to form more complex queries. The algorithms were implemented within the querying component of a new version of the software tool PATIKAweb (Pathway Analysis Tool for Integration and Knowledge Acquisition) and have proven useful for answering a number of biologically significant questions for large graph-based pathway databases.ConclusionThe PATIKA Project Web site is http://www.patika.org. PATIKAweb version 2.1 is available at http://web.patika.org.

Patikaweb provides a Web interface for retrieving and analyzing biological pathways in the Patika database, which contains data integrated from various prominent public pathway databases. It features a user-friendly interface, dynamic visualization and automated layout, advanced graph-theoretic queries for extracting biologically important phenomena, local persistence capability and exporting facilities to various pathway exchange formats.

Abstract. We present a new compound graph layout algorithm based on traditional force-directed layout scheme with extensions for nesting and other application-specific constraints. The algorithm has been successfully implemented within Patika, a pathway analysis tool for drawing complicated biological pathways with compartmental constraints and arbitrary nesting relations to represent molecular complexes and pathway abstractions. Experimental results show that execution times and quality of the produced drawings with respect to commonly accepted layout criteria and pathway drawing conventions are quite satisfactory.