Section: Overall Objectives
More than four hundred genomes have already been fully sequenced, among which around forty of eukaryotes including man and mouse. Obtaining the genomic sequences is, however, just a first step towards trying to understand how life develops and is sustained. After the sequencing, it is necessary to interpret the information contained in the genomes. One must identify the genes, that is, the regions coding for proteins, and then understand the function of these proteins and the network of interactions that control the expression of the genes according to the needs of an organism. Beyond that, it is important to understand how all the different structures sustaining life are established and maintained in the course of evolution. This evolutionary perspective cannot be ignored, as it allows us to compare and decipher the function of genes, the modification of metabolic pathways, the preservation and variation of signalling systems. In order to study life, it is essential not to limit oneself to genomic data. Other types of data that have become available recently are of equal importance and the information extracted from them must be compared and confronted with the results obtained from the analysis of genomic sequences. Examples of such data are the experimental data obtained by means of DNA microarrays, 2D gels, and mass spectrometry, as well as data on regulatory interactions extracted from the scientific literature.
Computational Biology (or Bioinformatics) is now recognised to play a key role in the process of turning experimental information into new biological knowledge. The HELIX group conducts research in this field with a rather broad spectrum of activities. The group develops new algorithms and applies them to bioinformatics objects, such as DNA and protein sequences, but also phylogenetic trees, as well as graphs which formalise gene interaction networks or metabolic pathways. From the biological point of view, the emphasis is put on comparative genomics and evolutionary biology.
One of the founding principles of the overall approach of the HELIX group is that every object of interest has to be explicitly represented and described, together with its relations to other objects. The group is thus performing an important activity in knowledge representation. A second founding principle is that the mathematical basis of our approaches should be clearly stated. An important part of the activity of HELIX therefore concentrates on the (re)formulation of biological questions into mathematical forms suitable for computer analysis. The fundamental problem is therefore how to design a model that should be simple enough to be practically useful but not so simple as to miss the subtleties of biological questions. The solution to this problem goes far beyond a simple remote collaboration between computer scientists and biologists and requires a real ``symbiosis'' between the two cultures.
The activities of HELIX are organised in two main research areas (Comparative and Functional genomics), each of them being divided into sub-topics.
The methodological aspects of the above research areas concern mainly knowledge representation, algorithmics, dynamic systems and statistics.
The HELIX project has the particularity that it bridges two geographical locations and two different bioinformatic cultures. While one group is located in Grenoble and has its origin in computer science, the two other groups reside in Lyon and have their roots in biology and biometry for one of them, and computer science and mathematics for the other. However, a long tradition of collaboration between the three groups confers coherence to the HELIX project, with respect both to computational methods and biological topics. Knowledge representation is certainly the best example of the methodological unity existing between the groups, while comparative genomics is at the heart of their biological concerns. Most of the research areas mentioned above involve HELIX members in both Grenoble and Lyon. In addition, members of other groups in the ``Laboratoire de Biométrie et Biologie Évolutive'' in Lyon, the associated group Swiss-Prot from the Swiss Institute of Bioinformatics in Geneva and the associated group from the Department of Computer Science of the University of São Paulo, Brazil, contribute to the research activities of HELIX, through co-supervision of PhDs and other forms of collaboration.
Participation in the development of two platforms plays an essential part in the integration of the various biological topics and methods developed in the HELIX project:
GenoStar is a bioinformatics platform for exploratory genomics which integrates methods and tools for modelling genomic data and knowledge developed both within and outside the project (Section 5.11 ).
PRABI is a Web server resource providing software which may be downloaded or used through facilities available on the Web. The HELIX group is one of the major participants in the development and maintenance of this platform, which is recognized at the national level as one of the RIO and Genopole platforms. The facilities offered by the PRABI cover such areas as genomics, structural biology, proteomics, health, and ecology. The director of the PRABI (C. Gautier) is a member of HELIX.