Max-Planck-Institut für Physik komplexer Systeme

International Workshop on 
Biological Evolution and Statistical Physics
May 10-14, 2000 

 

How to Extract Information from DNA-Chips?
H. Herzel, J. Schuchhardt, D. Beule, D. Holste
Institute of Biology, Humboldt University Berlin

A. Malik,  H. Eickhoff, H. Lehrach
MPI Molecular Genetics, Berlin-Dahlem

The simultaneous study of the expression of thousands of genes during a single experiment is possible with the hybridization of immobilized oligonucleotides or cDNAs. We present the statistical analysis of high density cDNA arrays with clones from a mouse unigene library and calibration spots from A. thaliana genes.

Using control spots and dilution series we quantify the reproducibility of the measurements. It turns out that overshining effects are weak and that there are multiplicative errors of about 10% over three orders of magnitude. Normalization strategies are introduced to remove systematic variations of the pin performance and  to compare different chips.

In order to reconstruct gene regulatory networks from expression data, clusters of coregulated genes have to be identified. Based on randomized data we derive tests to assess the significance of the resulting clusters. Using string search and multiple alignment via the
"Gibbs sampler" we identify regulatory sequences in upstream regions of gene clusters.

The ultimate goal of expression data analysis is the reconstruction of the underlying genetic networks. We apply techniques of "reverse engineering" to toy-models of genetic networks. It turns out that mutual information analysis allows the reconstruction of the network structure.

       
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