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Fabian Theis: "Modeling based on spatial expression patterns"

Wann 01.02.2010
von 11:15 bis 12:15
Wo FRIAS Seminarraum, Albertstraße 19
Kontakttelefon +49 (0)761 203 97418
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Fabian J. Theis
Computational Modeling in Biology, Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum Muenchen


Modeling based on spatial expression patterns

In systems biology, we aim at deriving models from multivariate biological observations in order to predict and establish biological knowledge and design new experiments. Ideally we want to work on quantitative data, available in a high number of homogeneous replicates. This may be possible in E. coli and yeast - however if we want to work on mammalian systems, we will often deal with heterogeneous, qualitative in-vivo data. Here we will derive models from data from in situ hybridization experiments. The presented work flow allows us to cope with both heterogeneity and the only qualitative nature of the data.

We develop and apply the method to derive a regulatory network describing the well-defined pattern of locally restricted gene expression domains around the mid- hindbrain boundary (MHB). This pattern is established and maintained by a regulatory network between several transcription and secreted factors that is not yet understood in full detail. We show that a Boolean analysis of the characteristic spatial gene expression patterns at the murine MHB reveals key regulatory interactions in this network. This approach allows us to predict also the interplay of the various regulatory interactions. In particular, we predict and then experimentally verify a maintaining rather than inducing effect of Fgf8 on Wnt1 expression.

Altogether, we will demonstrate that similar to temporal also spatial expression patterns can be used to gain information about the structure of regulatory networks.