Jacques van Helden - research activities

In 4 words : Bioinformatics of the regulation.

Detailed CV: http://www.scmbb.ulb.ac.be/~jvanheld/

Short description

I am developing computer programs for the analysis of regulatory pathways. I combine two complementary approaches : statistical analysis of regulatory sequences, and graph-based analysis of metabolic pathways.

Analysis of regulatory sequences

Since 1997, I have been developing statistical approaches for the analysis of regulatory sequences. I wrote programs which allow to address the following biological questions :

1. Starting from a set of co-regulated genes (e.g. clusters from microarray experiments), detect over-represented motifs in their upstream sequences, in order to infer the cis-acting elements involved in their co-regulation.
2. Starting from previously know transcription factor binding sites, scan the whole genome to detect genes potentially regulated by this transcription factor.

The programs are available on the web at:

http://rsat.ulb.ac.be/rsat/

Most complete genomes from Genbank are supported on the web site (there are currently 80 bacteria installed). Human genome will be installed soon.

In the near future, I envisage to extend this research in the following directions :

• extension of the methods for the analysis of higher eularyotes, with a particular interest in regulatory networks involved in development.
• detection of motif combinations : multi-criteria detection of complex features (composite elments, transcription initiation, ...).
• comparative genomics: analysis of the evolution of regulatory sequences

Analysis of metabolic pathways

Since 1998, I have been working on a database about metabolic pathways and their regulation. This project started in Shoshana Wodak's groups at the European Bioinformatics Institute and is now pursued in Shoshana Wodak's group at the Universite Libre de Bruxelles.

This database allows to address complex queries about metabolic regulation. In particular, we developed algorithms to infer metabolic pathways, starting from a set of enzyme-coding genes (e.g. a cluster of co-regulated genes detected by microarray experiments).

These algorithms are based on an assembly of a set of reactions (those catalyzed by the selected genes), and inference of missing steps. The approach is thus not based on the prior annotated pathways, and can be used for inferring novel pathways. Typical fields of application are

• analysis of drug response
• inference of degradation pathways for polluting molecules
• inference of alternative pathways by comparative genomics
• analysis of metabolism for bacteria living in extreme environments

Selected publications

1. van Helden, J., André, B. & Collado-Vides, J. (1998). Extracting regulatory sites from the upstream region of yeast genes by computational analysis of oligonucleotide frequencies. J Mol Biol 281(5), 827-42.
2. van Helden, J., André, B. & Collado-Vides, J. (2000). A web site for the computational analysis of yeast regulatory sequences. Yeast 16(2), 177-187.
3. van Helden, J., Olmo, M. & Perez-Ortin, J. E. (2000). Statistical analysis of yeast genomic downstream sequences reveals putative polyadenylation signals. Nucleic Acids Res 28(4), 1000-1010.
4. van Helden, J., Rios, A. F. & Collado-Vides, J. (2000). Discovering regulatory elements in non-coding sequences by analysis of spaced dyads. Nucleic Acids Res. 28(8):1808-18.
5. van Helden, J., Naim, A., Mancuso, R., Eldridge, M., Wernisch, L., Gilbert, D. & Wodak, S. J. (2000). Representing and analysing molecular and cellular function using the computer. Biol Chem 381(9-10), 921-35.
6. Gilbert, D., Schroeder, M. & van Helden, J. (2000). Interactive visualization and exploration of relationships between biological objects. Trends in Biotechnology 18(December), 487-495.
7. van Helden, J., Naim, A., Lemer, C., Mancuso, R., Eldridge, M. & Wodak, S. (2001). From molecular activities and processes to biological function. Briefings in Bioinformatics 2(1): 91-93.
8. van Helden, J., Gilbert, D., Wernisch, L., Schroeder, M. & Wodak, S. (2001). Applications of regulatory sequence analysis and metabolic network analysis to the interpretation of gene expression data. Lecture Notes in Computer Sciences 2066: 155-172.
9. Schroeder, M., Gilbert, D., van Helden, J. & Noy, P. (2002). Approaches to visualisation in bioinformatics: from dendrograms to Space Explorer. Information Science 139(1), 19-57.
10. van Helden, J. Wernisch, L., Gilbert, D., and Wodak, S. (2002). Graph-based analysis of metabolic networks. in Ernst Schering Research Foundation Workshop Volume 38: Bioinformatics and Genome Analysis. Editors: H.-W. Mewes, B. Weiss, H. Seidel Springer-Verlag, Berlin Heidelberg 2002.