In collaboration with Professor Bonin's group, Department for Medical Genetics Tübingen and Professor Dooley's group, Faculty for Clinical Medicine of the University Heidelberg, we analyze the transcription profiles of hepatocytes after HMG-Co-reductase-inhibitor treatment and after administration of TGF-beta, respectively.
For this purpose, we assign the hybridized oligos of the experiment to the reaction identifiers in the metabolic pathways. The mapping of oligos and reactions requires two steps: (I) automated assignment using EC-numbers or Kegg-orthology and (II) manual refinement.
For visual inspection of the data, a Metannogen module has been developed to import text files with tab separated expression values. The expression data is visualized within Kegg-Pathway maps.
An innovative novel feature is the possibility to apply mathematical functions to the expression data prior visualization. This allows, for example, computation of the arithmetic mean of several data columns or the logarithm of a column. The maps can be animated to illustrate time-dependence.
The analysis is complicated by the fact that also the untreated cell-population is undergoing major changes. The extend and time course of these changes are different for each oligo. Alterations of expression for control probes are not necessarily monotone. A root-mean-square based distance to identify those oligos where treatment has a significant effect is currently tested.
The time course of the expression patterns often indicates a certain strategy of the hepatocyte under the given conditions. In other cases, the reason for the observed changes still remain cryptic. For example the gluconeogenesis and glycolysis change in a reciprocal fashion after beta-TGF administration.
Researchers
Dr. Christoph Gille
Anja Karlstädt
in cooperation with Professor Bonin's group, Eberhard Karls Universität Tübingen, Medical Genetics and with Professor Dooley's group, Faculty for Clinical Medicine of the University Heidelberg.