Deducing corticotropin-releasing hormone receptor type 1 signaling networks from gene expression data by usage of genetic algorithms and graphical Gaussian models |
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Authors: | Dietrich Trümbach Cornelia Graf Benno Pütz Claudia Kühne Marcus Panhuysen Peter Weber Florian Holsboer Wolfgang Wurst Gerhard Welzl Jan M Deussing |
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Affiliation: | 1.Max Planck Institute of Psychiatry,Munich,Germany;2.Helmholtz Centre Munich, German Research Centre for Environmental Health, (GmbH) and Technical University Munich, Institute of Developmental Genetics, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE),Munich-Neuherberg,Germany |
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Abstract: | Background Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of complex and multifactorial psychiatric diseases such as anxiety and mood disorders. About 50-60% of patients with major depression show HPA axis dysfunction, i.e. hyperactivity and impaired negative feedback regulation. The neuropeptide corticotropin-releasing hormone (CRH) and its receptor type 1 (CRHR1) are key regulators of this neuroendocrine stress axis. Therefore, we analyzed CRH/CRHR1-dependent gene expression data obtained from the pituitary corticotrope cell line AtT-20, a well-established in vitro model for CRHR1-mediated signal transduction. To extract significantly regulated genes from a genome-wide microarray data set and to deduce underlying CRHR1-dependent signaling networks, we combined supervised and unsupervised algorithms. |
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