title: Analysis of Gene Expression Data by Systems Biology Methods creator: Koch, Yvonne subject: 570 subject: 570 Life sciences description: Perturbed regulation of programmed cell death (apoptosis) plays a major role in tumor development. The process of eliminating unwanted and damaged cells by apoptosis is based on complex molecule interactions. Studies of various diseases generally analyse patient samples in order to find markers or patterns in the data associated with the disease. However, for analysing biological processes like apoptosis, the focus of interest is to discover molecular mechanisms within cells and hence consider a different observational level. Simulation and analysis of differential equation models aid in elucidating complex interrelations on a mechanistic level. Nevertheless, interpretation of how molecules mechanisms give rise to a cellular process is complicated, time consuming and the bottleneck of systems biology research. In order to understand interactions and mechanisms of molecules involved in apoptosis on a systems level in the context of tumor development, this work combines analysis of patient data and analysis of molecular interactions. To achieve this aim, two different approaches were followed. The first approach analyses gene expression data of different tumor entities for their ability to undergo cell death in silico by simulation of a mathematical model of apoptosis. The second approach identifies hypothetical conditions required for apoptosis. To this end, a novel method for model analysis was developed to reveal multivariate control mechanisms of model behaviour. The method automatically suggests model components and their crucial interrelations for a specific system response. Conditions concerning certain apoptotic molecules and molecule relations could be confirmed. Moreover, interactions and relations were found, which suggest new hypotheses how apoptosis as a system is governed by a few molecules in a specific way. date: 2011 type: Dissertation type: info:eu-repo/semantics/doctoralThesis type: NonPeerReviewed format: application/pdf identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/11922/1/DissertationYvonneKoch.pdf identifier: DOI:10.11588/heidok.00011922 identifier: urn:nbn:de:bsz:16-opus-119227 identifier: Koch, Yvonne (2011) Analysis of Gene Expression Data by Systems Biology Methods. [Dissertation] relation: https://archiv.ub.uni-heidelberg.de/volltextserver/11922/ rights: info:eu-repo/semantics/openAccess rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html language: eng