Comparative analysis of topological patterns in different mammalian networks.

We have systematically analyzed various topological patterns comprising 1, 2 or 3 nodes in the mammalian metabolic, signal transduction and transcription networks: These patterns were analyzed with regard to their frequency and statistical over-representation in each network, as well as to their topological significance for the coherence of the networks. The latter property was evaluated using the pairwise disconnectivity index, which we have recently introduced to quantify how critical network components are for the internal connectedness of a network. The 1-node pattern made up by a vertex with a self-loop has been found to exert particular properties in all three networks.

An approach to evaluate the topological significance of motifs and other patterns in regulatory networks.

Background: The identification of network motifs as statistically over-represented topological patterns has become one of the most promising topics in the analysis of complex networks. The main focus is commonly made on how they operate by means of their internal organization. Yet, their contribution to a network's global architecture is poorly understood.

TRANSPATH--a high quality database focused on signal transduction.

TRANSPATH can either be used as an encyclopedia, for both specific and general information on signal transduction, or can serve as a network analyser. Therefore, three modules have been created: the first one is the data, which have been manually extracted, mostly from the primary literature; the second is PathwayBuilder, which provides several different types of network visualization and hence faciliates understanding; the third is ArrayAnalyzer, which is particularly suited to gene expression array interpretation, and is able to identify key molecules within signalling networks (potential drug targets). These key molecules could be responsible for the coordinated regulation of downstream events.

The pairwise disconnectivity index as a new metric for the topological analysis of regulatory networks.

Background: Currently, there is a gap between purely theoretical studies of the topology of large bioregulatory networks and the practical traditions and interests of experimentalists. While the theoretical approaches emphasize the global characterization of regulatory systems, the practical approaches focus on the role of distinct molecules and genes in regulation. To bridge the gap between these opposite approaches, one needs to combine 'general' with 'particular' properties and translate abstract topological features of large systems into testable functional characteristics of individual components.

EndoNet: an information resource about regulatory networks of cell-to-cell communication.

EndoNet is an information resource about intercellular regulatory communication. It provides information about hormones, hormone receptors, the sources (i.e.

Integrating pathway data for systems pathology.

The HumanPSD database on the complete proteomes of human, mouse and rat has been integrated with the databases TRANSFAC on gene regulation and TRANSPATH on signal transduction to provide a comprehensive systems biological platform for these organisms. As a next step, integration with PathoDB and PathoSign on pathologically relevant mutations is planned together with an extension beyond the limits of the individual cell, towards intercellular networks, by integrating the database EndoNet on hormonal networks as well. The overall aim is to come up with a platform that is suitable to provide knowledge for systems pathology, i.

Integrative content-driven concepts for bioinformatics "beyond the cell".

Bioinformatics has delivered great contributions to genome and genomics research, without which the world-wide success of this and other global ('omics') approaches would not have been possible. More recently, it has developed further towards the analysis of different kinds of networks thus laying the foundation for comprehensive description, analysis and manipulation of whole living systems in modern "systems biology". The next step which is necessary for developing a systems biology that deals with systemic phenomena is to expand the existing and develop new methodologies that are appropriate to characterize intercellular processes and interactions without omitting the causal underlying molecular mechanisms.

Topology of mammalian transcription networks.

We present a first attempt to evaluate the generic topological principles underlying the mammalian transcriptional regulatory networks. Transcription networks, TN, studied here are represented as graphs where vertices are genes coding for transcription factors and edges are causal links between the genes, each edge combining both gene expression and trans-regulation events. Two transcription networks were retrieved from the TRANSPATH database: The first one, TN_RN, is a 'complete' transcription network referred to as a reference network.

Mining the genome and regulatory networks.

A report on the 16th International Conference on Genome Informatics (GIW 2005), Yokohama, Japan, 19-21 December 2005.

TRANSPATH: an information resource for storing and visualizing signaling pathways and their pathological aberrations.

TRANSPATH is a database about signal transduction events. It provides information about signaling molecules, their reactions and the pathways these reactions constitute. The representation of signaling molecules is organized in a number of orthogonal hierarchies reflecting the classification of the molecules, their species-specific or generic features, and their post-translational modifications.

EndoNet: an information resource about endocrine networks.

EndoNet is a new database that provides information about the components of endocrine networks and their relations. It focuses on the endocrine cell-to-cell communication and enables the analysis of intercellular regulatory pathways in humans. In the EndoNet data model, two classes of components span a bipartite directed graph.

Consistent re-modeling of signaling pathways and its implementation in the TRANSPATH database.

The data model of the signaling pathways database TRANSPATH has been re-engineered to a three-layer model comprising experimental evidences and summarized pathway information, both in a mechanistically detailed manner, and a "semantic" projection for the abstract overview. Each molecule is described in the context of a certain reaction in the multidimensional space of posttranslational modification, molecular family relationships, and the biological species of its origin. The new model makes the data better suitable for reconstructing signaling pathways and networks and mapping expression data, for instance from microarray experiments, onto regulatory networks.

TRANSPATH: an integrated database on signal transduction and a tool for array analysis.

TRANSPATH is a database system about gene regulatory networks that combines encyclopedic information on signal transduction with tools for visualization and analysis. The integration with TRANSFAC, a database about transcription factors and their DNA binding sites, provides the possibility to obtain complete signaling pathways from ligand to target genes and their products, which may themselves be involved in regulatory action. As of July 2002, the TRANSPATH Professional release 3.