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Prediction of cardiac transcription networks based on molecular data and complex clinical phenotypes

Item Type:Article
Title:Prediction of cardiac transcription networks based on molecular data and complex clinical phenotypes
Creators Name:Toenjes, M. and Schueler, M. and Hammer, S. and Pape, U.J. and Fischer, J.J. and Berger, F. and Vingron, M. and Sperling, S.
Abstract:We present an integrative approach combining sophisticated techniques to construct cardiac gene regulatory networks based on correlated gene expression and optimized prediction of transcription factor binding sites. We analyze transcription levels of a comprehensive set of 42 genes in biopsies derived from hearts of a cohort of 190 patients as well as healthy individuals. To precisely describe the variety of heart malformations observed in the patients, we delineate a detailed phenotype ontology that allows description of observed clinical characteristics as well as the definition of informative meta-phenotypes. Based on the expression data obtained by real-time PCR we identify specific disease associated transcription profiles by applying linear models. Furthermore, genes that show highly correlated expression patterns are depicted. By predicting binding sites on promoter settings optimized using a cardiac specific chromatin immunoprecipitation data set, we reveal regulatory dependencies. Several of the found interactions have been previously described in literature, demonstrating that the approach is a versatile tool to predict regulatory networks.
Keywords:Algorithms, Binding Sites, Cardiac Myocytes, Cluster Analysis, Cohort Studies, Computational Biology, Congenital Heart Defects, Gene Expression Profiling, Gene Regulatory Networks, Linear Models, Phenotype, Predictive Value of Tests, Reproducibility of Results, Reverse Transcriptase Polymerase Chain Reaction, Statistical Data Interpretation, Transcription Factors/
Source:Molecular BioSystems
Publisher:Royal Society of Chemistry
Page Range:589-598
Date:June 2008
Official Publication:https://doi.org/10.1039/b800207j
PubMed:View item in PubMed

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