Showing papers by "Edgar Wingender published in 2008"

The TRANSFAC project as an example of framework technology that supports the analysis of genomic regulation

Abstract: Since its beginning as a data collection more than 20 years ago, the TRANSFAC project underwent an evolution to become the basis for a complex platform for the description and analysis of gene regulatory events and networks. In the following, I describe what the original concepts were, what their present status is and how they may be expected to contribute to future system biology approaches.

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

Abstract: 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. Here, we propose a new topological parameter – the pairwise disconnectivity index of a network's element – that is capable of such bridging.

ExPlain™: finding upstream drug targets in disease gene regulatory networks

Abstract: Different signal transduction pathways leading to the activation of transcription factors (TFs) converge at key molecules that master the regulation of many cellular processes. Such crossroads of signalling networks often appear as “Achilles Heels” causing a disease when not functioning properly. Novel computational tools are needed for analysis of the gene expression data in the context of signal transduction and gene regulatory pathways and for identification of the key nodes in the networks. An integrated computational system, ExPlain™ (www.biobase.de) was developed for causal interpretation of gene expression data and identification of key signalling molecules. The system utilizes data from two databases (TRANSFAC® and TRANSPATH®) and integrates two programs: (1) Composite Module Analyst (CMA) analyses 5′-upstream regions of co-expressed genes and applies a genetic algorithm to reveal composite modules (CMs) consisting of co-occurring single TF binding sites and composite elements; (2) ArrayAnalyzer™ ...

[Differentiation of osteogenetic cells: systems and regulators].

Abstract: Bone formation comprises a complex but ordered sequence of events, beginning with the proliferation of chondrogenic and osteogenic precursor cells followed by their subsequent differentiation, ultimately leading to extracellular matrix maturation and mineralisation. Several models have been established which recreate discrete elements of this network. Factors induce ectopic bone formation, when implanted into muscle pouches, have been characterized as members of the TGF-beta-superfamily. Detailed information about the course of OB-differentiation has been obtained from an in vitro model system. The process of mineralisation was found to consist of three distinct time periods: a proliferative phase, a period of extracellular matrix maturation and mineralisation. The development of each states depends on each other. This model is not as complex as the whole organ and cannot of course lead to any conclusion about the kinetic differentiation path of a cell in its normal spatial environment. Different organ culture systems are described and through the application of sensitive methods the differentiation can be studied in the normal spatial environment. The cascade of events in the differentiation process must be strictly regulated. Hormones and growth factors in many cases show a bone-forming and/or bone-resorbing action. The effects of the classical calcium regulating hormones Vitamin D and PTH on OB-differentiation are reviewed. A large number of growth factors have been shown to effect OB. Growth factors, that have been isolated from the bone matrix are of particular interest to bone formation.

Building a knowledge base for systems pathology.

Abstract: Translating the exponentially growing amount of omics data into knowledge usable for a personalized medicine approach poses a formidable challenge. In this article-taking diabetes as a use case-we present strategies for developing data repositories into computer-accessible knowledge sources that can be used for a systemic view on the molecular causes of diseases, thus laying the foundation for systems pathology.