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Abstract:
This thesis is concerned with revealing regulation of gene expression. The basic motivation
behind our work is that gene regulation can be better resolved when analyzed in a cellular
context of the upstream signaling pathway and known regulatory targets. Our source
of data are perturbation experiments, which are performed on pathway components and
induce changes in gene expression. In such a way, they connect the signaling pathway to
its downstream target genes. This chapter starts with an introduction to the cellular con-
text considered in the thesis (section 1.1) and the principles of perturbation experiments
(section 1.2). We end with a concise summary of three approaches that comprise this
thesis. The approaches tackle various problems in the process of revealing context-speci c
regulatory networks (section 1.3). We deal with di erential expression analysis of the per-
turbation data, enhanced with known transcription factor targets serving as examples of
di erential genes (chapter 2), pathway model-based planning of informative perturbation
experiments (chapter 3), and nally, with deregulation analysis, i.e., comparing changes
in gene regulation between two di erent cell populations (chapter 4).
