Laboratory of Bioinformatic Analysis for Genomic and Metabolism

The Comparative Genomics Atelier is a bio-informatics group for which the principal objective is to develop the informatics tools necessary for the extraction of significant information from the data from microbial genomes which are currently available or are in the process of being sequenced. The group consists principally of biologists who have developed a pronounced interest in informatics (mainly programming and databases) and/or in bio-analysis (interpretation of the results of genomic analysis). The activity of the AGC thus includes both informatics developments (some of which result from specific collaborations with computer scientists, statisticians and/or mathematicians), and biological analysis of the results obtained with informatics tools (developed by our group or integrated into our environment). The permanent interaction with the users of the tools which we develop, (mainly biologists who work in laboratories), is a primordial activity of the AGC. These exchanges, which are numerous and regular, permit us to enrich our biological understanding of the diverse bacteria studied. It is also the most efficient means of developing our platform for the annotation and analysis of prokaryotic genomes, MicroScope, by integrating the new strategies which are indispensable for functional annotation of genes, and the functionalities of the MaGe (Magnifying Genome) graphic interface, destined to explore genomic data of a diverse nature.

Missions

The raw sequencing data have little interest as such. What is important is the biological knowledge that can be extracted from them. The principal role of bioinformatics is to assist the biologists in this task, particularly by integrating data from very diverse origins (raw sequencing data, results of in silico analysis, data from generic or specific databases, data from large-scale experiments such as experiments on the transcriptome, the proteome, etc.). The missions of the AGC fall into the framework of this logic:

• Developing methods and tools for analysis in silico of genomic data from prokaryotic organisms. These data are integrated into the automatic annotation “pipeline” of the bacterial genomes studied. Some of these data are placed on Web servers which are accessible to the scientific community.
• Setting up databases for comparative genomics: these include relational databases for the comparative annotation of bacterial genomes, metabolic databases for the exploration of metabolic networks of the genomes studied (MicroCyc), and finally a knowledge database which integrates several biological levels (genes and their neighbors, metabolism, and phenotyping results when available).
• Since autumn of 2004 and with support from the informatics group at Genoscope (directed by Claude Scarpelli), the AGC has been developing an infrastructure for the analysis, annotation and management of bacterial sequencing data produced at Genoscope (priority) or from other sequencing centers (Pasteur Institute, Sanger Center, DOE/JGI). The missions associated with the MicroScope platform are the following:
  1. To execute the ensemble of analysis tools and create new thematic, genomic and metabolic databases.
  2. To organize 3-4 day training programmes for users of the MaGe interface tools.
  3. To provide continuous assistance to experts from a group in their annotation tasks. and
  4. To update data in thematic databases (similarities, calculation of synteny, etc). The MicroScope databases are accessible via the Web server for MaGe.
• Participating in genomic projects which are ongoing in our own UMR (Mixed Research Unit), “Metabolic Genomics”, or projects from the MicroScope platform chosen for their scientific or strategic interest.

Research axes : The research themes developed are intimately linked to the activities of the MicroScope platform and include both methodological and applications aspects:

• Methods for functional annotation and comparative genomics: the principle is to add to knowledge on the genome of a species by using information which is available for other species, by taking advantage of the conservation of certain properties between species.
• Databases for genomics and representation of knowledge : this includes reflections on models for specific data and the development of an exploratory genome platform, GenoStar (GenoLink module).
  • Conception of servers for methods and databases.
  • Bacterial genomics: statistics applied to genomic data (nucleic acids and proteins), detection of genomic islands, evolutionary mechanisms (conservation of syntenies in bacterial genomes, fissions/fusions of genes), study of ORFans.
  • Bacterial metabolism: prediction and comparison of metabolic networks; characterization of “orphan enzymes”.

Partnerships and collaborations

• Collaborations with numerous biology laboratories in the framework of the “MicroScope” projects: http://www.genoscope.cns.fr/agc/microscope
• GDR Partner: “Metabolism of arsenic in prokaryotes: from resistance to detoxification”
• Collaborations with the Helix team, Informatique et Génomique, from l’INRIA Rhône- Alpes (Grenoble)
• Collaborations with the SwissProt team from the “Swiss Institute of Bioinformatics” (SIB) in Geneva (HAMAP project: “High-quality Automated and Manual Annotation of microbial Proteomes”)
• Exchanges with the members of the “Genome Review” project of EBI at Cambridge
• Collaborations with the SRI International group (California, USA) for the set-up and evolution of BioCyc
• Collaborations with the UMR groups, Metabolic thesaurus and Cloaca maxima

Results

AMIGene
MaGe
Micheck
MicroCyc
MicrOscOpe