Publications

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64 Publications visible to you, out of a total of 64

Abstract (Expand)

MOTIVATION: Statins are the most widely used cholesterol-lowering drugs. The primary target of statins is HMG-CoA reductase, a key enzyme in cholesterol synthesis. However, statins elicit pleitropic responses including beneficial as well as adverse effects in the liver or other organs. Today, the regulatory mechanisms that cause these pleiotropic effects are not sufficiently understood. RESULTS: In this work, genome-wide RNA expression changes in primary human hepatocytes of six individuals were measured at up to six time points upon atorvastatin treatment. A computational analysis workflow was applied to reconstruct regulatory mechanisms based on these drug-response data and available knowledge about transcription factor (TF) binding specificities and protein-drug interactions. Several previously unknown TFs were predicted to be involved in atorvastatin-responsive gene expression. The novel relationships of nuclear receptors NR2C2 and PPARA on CYP3A4 were successfully validated in wet-lab experiments. AVAILABILITY: Microarray data are available at the Gene Expression Omnibus (GEO) database at www.ncbi.nlm.nih.gov/geo/, under accession number GSE29868. CONTACT: andreas.zell@uni-tuebingen.de; adrian.schroeder@uni-tuebingen.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Authors: A. Schroder, J. Wollnik, C. Wrzodek, A. Drager, M. Bonin, O. Burk, M. Thomas, W. E. Thasler, U. M. Zanger, A. Zell

Date Published: 14th Jul 2011

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Authors: A. Schroder, J. Wollnik, C. Wrzodek, A. Drager, M. Bonin, O. Burk, M. Thomas, W. E. Thasler, U. M. Zanger, A. Zell

Date Published: 14th Jul 2011

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Authors: H. A. Piwowar, T. J. Vision, M. C. Whitlock

Date Published: 20th May 2011

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Authors: M. Carmen Herrera, Estrella Duque, José J. Rodríguez-Herva, Ana M. Fernández-Escamilla, Juan L. Ramos

Date Published: 2010

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Authors: Dmitry Devetyarov, Ilia Nouretdinov

Date Published: 2010

Publication Type: Not specified

Abstract (Expand)

Systems Biology Markup Language (SBML) is the leading exchange format for mathematical models in Systems Biology. Semantic annotations link model elements with external knowledge via unique database identifiers and ontology terms, enabling software to check and process models by their biochemical meaning. Such information is essential for model merging, one of the key steps towards the construction of large kinetic models. SemanticSBML is a tool that helps users to check and edit MIRIAM annotations and SBO terms in SBML models. Using a large collection of biochemical names and database identifiers, it supports modellers in finding the right annotations and in merging existing models. Initially, an element matching is derived from the MIRIAM annotations and conflicting element attributes are categorized and highlighted. Conflicts can then be resolved automatically or manually, allowing the user to control the merging process in detail.

Authors: Firstname Lastname, Jannis Uhlendorf, Timo Lubitz, Marvin Schulz, Edda Klipp, Wolfram Liebermeister

Date Published: 17th Nov 2009

Publication Type: Not specified

Abstract (Expand)

BACKGROUND: During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples. RESULTS: Surprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2 hours, and changes in antibiotic biosynthesis genes are delayed relative to the metabolic rearrangements. Furthermore, global variation in morphogenesis genes indicates an involvement of cell differentiation pathways in the decision phase leading up to the commitment to antibiotic biosynthesis. CONCLUSIONS: Our study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological setting.

Authors: Kay Nieselt, Florian Battke, Alexander Herbig, Per Bruheim, Alexander Wentzel, Øyvind M Jakobsen, Håvard Sletta, Mohammad T Alam, Maria E Merlo, Firstname Lastname, Firstname Lastname, Edward R Morrissey, Miguel A Juarez-Hermosillo, Antonio Rodríguez-García, Merle Nentwich, Louise Thomas, Mudassar Iqbal, Roxane Legaie, William H Gaze, Gregory L Challis, Ritsert C Jansen, Lubbert Dijkhuizen, David A Rand, David L Wild, Michael Bonin, Jens Reuther, Wolfgang Wohlleben, Margaret C M Smith, Nigel J Burroughs, Juan F Martín, David A Hodgson, Eriko Takano, Rainer Breitling, Trond E Ellingsen, Elizabeth M H Wellington

Date Published: 28th May 2009

Publication Type: Not specified

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