Biomedical subjects

Nico Voss

Publications and source records attributed to Nico Voss.

5 recordsLinked to original sources

PubMed2006

Beyond microarrays: find key transcription factors controlling signal transduction pathways.

BACKGROUND: Massive gene expression changes in different cellular states measured by microarrays, in fact, reflect just an "echo" of real molecular processes in the cells. Transcription factors constitute a class of the regulatory molecules that typically require posttranscriptional modifications or ligand binding in order to exert their function. Therefore, such important functional changes of transcription factors are not directly visible in the microarray experiments. RESULTS: We developed a novel approach to find key transcription factors that may explain concerted expression changes of specific components of the signal transduction network. The approach aims at revealing evidence of positive feedback loops in the signal transduction circuits through activation of pathway-specific transcription factors. We demonstrate that promoters of genes encoding components of many known signal transduction pathways are enriched by binding sites of those transcription factors that are endpoints of the considered pathways. Application of the approach to the microarray gene expression data on TNF-alpha stimulated primary human endothelial cells helped to reveal novel key transcription factors potentially involved in the regulation of the signal transduction pathways of the cells. CONCLUSION: We developed a novel computational approach for revealing key transcription factors by knowledge-based analysis of gene expression data with the help of databases on gene regulatory networks (TRANSFAC and TRANSPATH. The corresponding software and databases are available at http://www.gene-regulation.com.

Binding Sites↗

PubMed2006

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. Reactions are similarly hierarchically organized in a three-layer architecture, differentiating between reactions that are evidenced by individual publications, generalizations of these reactions to construct species-independent 'reference pathways' and the 'semantic projections' of these pathways. A number of search and browse options allow easy access to the database contents, which can be visualized with the tool PathwayBuildertrade mark. The module PathoSign adds data about pathologically relevant mutations in signaling components, including their genotypes and phenotypes. TRANSPATH and PathoSign can be used as encyclopaedia, in the educational process, for vizualization and modeling of signal transduction networks and for the analysis of gene expression data. TRANSPATH Public 6.0 is freely accessible for users from non-profit organizations under http://www.gene-regulation.com/pub/databases.html.

Computer Graphics↗

PubMed2005

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. The second one, TN_p53, displays a particular transcriptional sub-network centered at p53 gene. We found these networks to be fundamentally non-random and inhomogeneous. Their topology follows a power-law degree distribution and is best described by the scale-free model. Shortest-path-length distribution and the average clustering coefficient indicate a small-world feature of these networks. The networks show the dependence of the clustering coefficient on the degree of a vertex, thereby indicating the presence of hierarchical modularity. Clear positive correlation between the values of betweenness and the degree of vertices has been observed in both networks. The top list of genes displaying high degree and high betweennes, such as p53, c-fos, c-jun and c-myc, is enriched with genes that are known as having tumor-suppressor or proto-oncogene properties, which supports the biological significance of the identified key topological elements.

Animals↗

PubMed2004

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.

Algorithms↗

PubMed2003

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 3.2 contains about 9800 molecules, >1800 genes and >11 400 reactions collected from approximately 5000 references. With the ArrayAnalyzer, an integrated tool has been developed for evaluation of microarray data. It uses the TRANSPATH data set to identify key regulators in pathways connected with up- or down-regulated genes of the respective array. The key molecules and their surrounding networks can be viewed with the PathwayBuilder, a tool that offers four different modes of visualization. More information on TRANSPATH is available at http://www.biobase.de/pages/products/databases.html.

Animals↗