Email updates

Keep up to date with the latest news and content from BMC Bioinformatics and BioMed Central.

Open Access Highly Accessed Methodology article

Inferring the role of transcription factors in regulatory networks

Philippe Veber1*, Carito Guziolowski1, Michel Le Borgne2, Ovidiu Radulescu13 and Anne Siegel4

Author Affiliations

1 Centre INRIA Rennes Bretagne Atlantique, IRISA, Rennes, France

2 Université de Rennes 1, IRISA, Rennes, France

3 Université de Rennes 1, IRMAR, Rennes, France

4 CNRS, UMR 6074, IRISA, Rennes, France

For all author emails, please log on.

BMC Bioinformatics 2008, 9:228  doi:10.1186/1471-2105-9-228

Published: 6 May 2008

Abstract

Background

Expression profiles obtained from multiple perturbation experiments are increasingly used to reconstruct transcriptional regulatory networks, from well studied, simple organisms up to higher eukaryotes. Admittedly, a key ingredient in developing a reconstruction method is its ability to integrate heterogeneous sources of information, as well as to comply with practical observability issues: measurements can be scarce or noisy. In this work, we show how to combine a network of genetic regulations with a set of expression profiles, in order to infer the functional effect of the regulations, as inducer or repressor. Our approach is based on a consistency rule between a network and the signs of variation given by expression arrays.

Results

We evaluate our approach in several settings of increasing complexity. First, we generate artificial expression data on a transcriptional network of E. coli extracted from the literature (1529 nodes and 3802 edges), and we estimate that 30% of the regulations can be annotated with about 30 profiles. We additionally prove that at most 40.8% of the network can be inferred using our approach. Second, we use this network in order to validate the predictions obtained with a compendium of real expression profiles. We describe a filtering algorithm that generates particularly reliable predictions. Finally, we apply our inference approach to S. cerevisiae transcriptional network (2419 nodes and 4344 interactions), by combining ChIP-chip data and 15 expression profiles. We are able to detect and isolate inconsistencies between the expression profiles and a significant portion of the model (15% of all the interactions). In addition, we report predictions for 14.5% of all interactions.

Conclusion

Our approach does not require accurate expression levels nor times series. Nevertheless, we show on both data, real and artificial, that a relatively small number of perturbation experiments are enough to determine a significant portion of regulatory effects. This is a key practical asset compared to statistical methods for network reconstruction. We demonstrate that our approach is able to provide accurate predictions, even when the network is incomplete and the data is noisy.