Högskolan i Skövde

In recent time particular interest has been drawn to the inference of gene regulatory networks from microarray gene expression data. But despite major improvements with data based methods, the network reconstruction from expression data alone still presents a computationally complex (NP-hard) problem. In this work it is incorporated additional information – regulatory motifs from yeast, when inferring a gene regulatory network for mouse genes. It was put forward the hypothesis that regulatory patterns analogous to these motifs are present in the set of mouse genes and can be identified by comparing yeast and mouse genes in terms of sequence similarity or Gene Ontology (The Gene Ontology Consortium 2000) annotations.

In order to examine this hypothesis, small permutations of genes with high similarity to such yeast gene regulatory motifs were first tested against simple data-driven regulatory networks by means of consistency with the expression data. And secondly, using the best scored interactions provided by these permutations it were then inferred networks for the whole set of mouse genes.

The results showed that individual permutations of genes with a high similarity to a given yeast motif did not perform better than low scored motifs and that complete networks, which were inferred from regulatory interactions provided by permutations, did also neither show any noticeable improvement over the corresponding data-driven network nor a high consistency with the expression data at all.

It was therefore found that the hypothesis failed, i.e. neither the use of sequence similarity nor searching for identical functional annotations between mouse and yeast genes allowed to identify sets of genes that showed a high consistency with the expression data or would have allowed for an improved gene regulatory network inference.