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Bioinformatics Advance Access published online on September 13, 2005
Bioinformatics, doi:10.1093/bioinformatics/bti662
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© The Author (2005). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received July 14, 2005
Revised September 2, 2005
Accepted September 3, 2005

Article

Non-transcriptional pathway features reconstructed from secondary effects of RNA interference

Florian Markowetz 1*, Jacques Bloch 1, and Rainer Spang 1

1 Max Planck Institute for Molecular Genetics, Dept. Computational Molecular Biology, Computational Diagnostics Group, Ihnestrasse 63-73, 14195 Berlin

* To whom correspondence should be addressed.
Florian Markowetz, E-mail: florian.markowetz{at}molgen.mpg.de


  Abstract

Motivation: Cellular signaling pathways, which are not modulated on a transcriptional level, cannot be directly deduced from expression profiling experiments. The situation changes, when external interventions like RNA interference or gene knock-outs come into play. Even if the expression of the signaling genes is not changed, secondary effects in downstream genes shed light on the pathway, and allow partial reconstruction of its topology.

Results: We introduce an algorithm to infer non-transcriptional pathway features based on differential gene expression in silencing assays. We demonstrate the power of our algorithm in the controlled setting of simulation studies, and explain its practical use in the context of an RNAi data set investigating the response to microbial challenge in Drosophila melanogaster.


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