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The Microme Project: A Knowledge-Based Bioinformatics Framework for Microbial Pathway Genomics

Final Report Summary - MICROME (The Microme Project: A Knowledge-Based Bioinformatics Framework for Microbial Pathway Genomics)

Executive Summary:
The future of sustainable economic development depends on the discovery and exploitation of new biological catalysts able to perform, at a minimal energy cost and in an environmentally friendly manner, synthesis and degradation reactions that have been so far the near exclusive realm of industrial and chemical engineering. The prokaryotic world is the largest reservoir of enzymatic activities in the biosphere, but the vast majority of this treasure trove has not yet been identified, either because of our inability to access sequence information from bacterial species, or because our ability to identify and functionally characterize deciphered sequences is lagging behind our ability to generate raw, uncharacterised data. The last few years have witnessed the development of new sequencing technologies and accelerated production of DNA sequence, both the complete genomes of singular organisms and (harder-to-interpret) “metagenomes” extracted from environmental samples; indeed, the determination of DNA sequence can no longer be considered a relevant bottleneck to scientific advance. Huge virgin territories of “natural” chemistry are thus opening up for exploration. Unfortunately, this massive influx of sequence data stands in sharp contrast to the rate of discovery of new biochemical reactions, which remains low.
The Microme project brought together a unique alliance of leading computational biologists, experimental microbiologists, and SMEs focused on white and green biotechnology applications to develop solutions to the primary problems limiting the full scientific and biotechnological exploitation of the wealth of knowledge derivable from bacterial genomes. Specifically, the consortium aimed at developing a coherent computational platform for extracting, structuring and storing, in updatable, accessible and computable forms, the enzymatic complement encoded in bacterial genomes; using this information to generate computational models of bacterial metabolism; and applying this knowledge for evolutionary and biotechnological analyses.
During the four years of its existence, Microme has (i) driven extensive, systematic work to improve the annotation of reference genomes (both through manual curation and through improvements to mechanisms for automatically inferred annotation) (ii) produced extensive data sets, updated at regular intervals, describing the known reaction complement of all 7000+ sequenced bacterial genomes submitted to the public archives, using standardised database identifiers, descriptive vocabularies and data formats; and a set of curated species-specific pathway assemblies (iii) generated metabolic models from the SSPAs, which perform well compared with other automatically-generated models, and which are can be automatically updated with each new release of improved data sets (iv) generated a tool for evolutionary analysis of metabolic functions (v) developed applied new tools for a number of important problems of biotechnological relevance including retrobiosynthesis. An new integrated web portal has been developed to provide access to these data and tools. In addition, a number of meetings have been held aimed at training scientist in the use of the tools developed in Microme (and others, that are complementary in purpose) for the analysis of microbial genomes. Finally, all data generated in Microme is publicly available, regularly updated, and shared with other public data resources, to maximise its usefulness to the research community. Through these activities, Microme increased our understanding of microbial metabolism, and opened the way to its exploitation in downstream applications.
Project Context and Objectives:
The development of systems biology is among the most exciting developments of the post-genomic era. A key element of this is the development of global metabolic models, which must be founded on a high-quality and comprehensive set of curated pathway information. While Europe has contributed significantly to the development of many world-class molecular biology and chemistry databases, the necessary foundation of any pathways resource, this expertise was not exploited in the form of a resource for microbial pathway data. Prior to Microme, the most outstanding resources of this kind were BioCyc (in the USA) and KEGG (in Japan); the Microme project positioned European science on a par with its major international beneficiaries; and exploited the wealth of knowledge of microbial metabolism possessed within the European research and development communities. To deal with these challenges, we assembled a consortium representing expertise from throughout Europe (with 1 beneficiary from Belgium, 3 beneficiaries from France; 3 beneficiaries from Germany; 1 beneficiary from Greece; 1 beneficiary from Israel; 2 beneficiaries from Spain; 1 beneficiary from Switzerland; and 2 beneficiaries from the United Kingdom) to establish and exploit this resource. The consortium represented world-class European expertise in genome sequencing, bioinformatics infrastructure, computational biology, microbiology, and metabolic engineering; and had extensive links to the wider scientific community through formal and informal collaborations throughout these domains.
The Microme project assembled and developed a bioinformatics infrastructure, together with a projection and curation process, aimed at generating complete pathway assemblies from genome annotations, on to whole-cell metabolic models for a subset of species. Specifically, curated reference pathways were projected onto microbial genomes to define complete pathway assemblies for each species. These pathway assemblies were then used for the construction of stoichiometric models. Hypotheses generated by these activities were tested experimentally. In particular, metabolic models were systematically assessed and validated using growth phenotype data generated within the project. Data from the assemblies, models, comparative analyses and experimental validation were used to improve the definition of reference pathways.
The resulting pathways and models were stored within a single curated resource, called “Microme”. This resource enables comparative and evolutionary analyses on metabolism, which, beyond their intrinsic scientific value, facilitate the refinement of reconstructed pathways and models and the reconstruction of new ones. Finally, the usefulness of Microme for metabolic engineering and synthetic biology objectives was explored through a small set of focused proof-of-concept efforts.

The five key Microme objectives were:

1. The development of a software infrastructure capable of supporting the curation, projection and display of microbial pathway data.
2. The delivery of a set of genome-scale metabolic networks, each for a given bacterial species; these so-called pathway assemblies are structured in terms of the pathway variants represented in that organism.
3. The delivery of genome-scale, constraint-based metabolic models derived for a subset of the species included in Microme.
4. The development of a suite of software tools exploiting pathways and models from the Microme resource for comparative analyses and metabolic engineering purposes.
5. The development of a web portal integrating curated pathways, curated and projected pathway assemblies, and stoichiometric models for bacterial data.


The Microme project was shaped as a four-year large collaborative project developed along 8 workpackages conducted by 15 scientific partners.

WP1 and WP2 were focused on the establishment of the pathway repository and projection system. WP3 was focused on using these projected networks to construct metabolic models. WP4 was focused on the comparative and evolutionary analysis of metabolic pathways, developing methods and software, and producing targeted case studies that will demonstrate the utility of the database and associated tools. WP5 developed metabolic engineering strategies to exploit the Microme resource in the service of white biotechnology and environmental sustainability objectives. The work performed in the context of WPs 3, 4 and 5 not only fed off the pathways repository established in WP1 and 2, but also contributed the repository’s content, and to the development of new/improved tools for pathway integrity checking and projection. WP6 integrated this content in a single web portal. WP 7 and 8 addressed outreach/training, and internal project management, respectively.
The consortium was coordinated by Paul Kersey (pkersey@ebi.ac.uk) and managed by Pascal Kahlem (pkahlem@ebi.ac.uk) at the European Bioinformatics Institute. An executive committee was formed to work with the coordinator on the overall strategic development of the project. It consisted of the project coordinator Paul Kersey, Claudine Médigue (WP2/WP7 coordinator), Christos Ouzounis (WP4 coordinator), Victor de Lorenzo (WP5 coordinator), Vitor Martins Dos Santos (WP3 coordinator). In addition, to provide external feedback on the progress of the project, the executive committee created a scientific advisory board (SAB), bringing together scientists expert in the fields of systems biology, computer sciences and biology. The members of the SAB were invited to annual general meetings to learn of the project’s activities and provide feedback. The members of the SAB were: Nikos Kyprides (DOE, JGI Production Genomics Facility, USA), Peter d’Eustachio (New York University, USA), Christopher Henry (Argonne National Laboratory, Argonne, Illinois, USA) and David Ussery (DTU, Denmark).
Project Results:
The project was structured in two phases. The first half of the project was dedicated to the establishment of the resource, through the development of the core infrastructure in WP1 and WP6, the automatic bootstrapping of the reference pathways repository, and an initial curation jamboree to prepare the resource for public launch, scheduled after the first year. Application-oriented beneficiaries participated actively in their specification and development during that first phase; and developed methods and tools using test or external data. During the second phase of the project we concentrated on the establishment of the mature data production, curation and release cycles; and the operation of downstream applications feeding off the Microme repository. At launch, Microme specifically contained the minimum data required to enable the commencement of operation of the model building and comparative analysis tools developed in WP3 and WP4.

WP1 was dedicated to the development of the pathway repository and associated software infrastructure. This included the development of a database model, a curation interface, automated scripts for data integrity checking, and tools for projection across species. Risk was reduced by building on the software developed in the context of the Reactome project (http://www.reactome.org) which has already proved capable of performing many of these tasks in the context of human pathway biology (the Microme consortium included EMBL-EBI, a partner in the Reactome project); and further integrating additional tools capable of performing analysis specific to microbial pathways

WP2 was focused on the population of the pathways database, using the infrastructure developed in WP1. In the first phase of the project, Microme populated with reference data available from existing resources, either provided by consortium members (e.g. UniPathway, BioPath, Reactome) or from other, publicly available resources.

We first used computational approaches to fit this data to the Microme data model; then, beneficiaries contributed to a curation jamboree where pathways of interest checked, corrected and completed as necessary, resulting in the production of the launch data set. At this stage, Microme contained sufficient information to allow the creation of high-quality stoichiometric models for reference species Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa and Acinetobacter baylyi to enable comparative analyses on a significant set of reference pathways from central metabolism.

In the second phase of the project, the quantity and quality of the data in the resource were increased through a continuous (and tightly coupled) process of pathway curation and projection. Curation occurred according to two primary models: (i) curation of complete pathway assemblies in reference genomes and (ii) expert curation of reference pathways across the full spectrum of species. The initial focus on pathways was additionally supplemented by a new focus on the construction of a new integrative repository for individual reactions constructed using multiple methods applied to thousands of genomes. Comprehensive reaction sets are essential for constructing metabolic models, the focus of work package 3.

In WP3, Microme developed a pipeline for the automated reconstruction, testing and refinement of genome-scale, constraint-based metabolic models, by combining and extending software platforms developed by TAU and WU, and applying these to the data sets generated in WP2. Results from the models was verified against the initial annotation, and against experimental data (generated using the Biolog platform) indicating the viability of specific bacteria on particular substrates; in this way, anomalies could be identified and used as a focus for subsequent curation activities; and released models could be confirmed as experimentally validated. A repository of biological facts was developed to store experimental information useful in the validation process. A total of 29 stoichiometric models were publicly released on the Microme website by the end of the project.

WP4 focused on the development of software tools performing a variety of novel comparative and evolutionary analyses of pathways and models that become possible because of the formal structure and spread of Microme data. The initial effort focused on the theoretical design of that comparative analysis layer, resulting in a set of specification documents. Simultaneously, computational methods for pathways comparison, for pathways-based phylogenetic reconstructions, for the inference of growth environments from models, for genomic context analysis and for the comparative characterization of model behaviour have been developed. After the launch of the Microme resource, these methods were applied to larger datasets and taxonomic ranges, and refined accordingly. The corresponding software tools were integrated within the Microme portal: Microscope Phyloprofile, RSAT and TeBacTen. Additional tools are access-restricted until publication, but have been reported within the deliverables of the WP4 (http://www.microme.eu/documentation/deliverables) and distributed among the consortium members, together with the results of a few “reference” analyses – such as the evolutionary stratification of pathways. In addition, specific comparative analyses were performed to facilitate the work of pathways curators during the jamborees.

WP5 demonstrated the usefulness of the Microme resource in several biotechnological applications. Four small-scale “proof-of-concept” projects were pursued; each designed to make good use of the set of pathways and models produced by WP2 by following a simple idea. Two new software tools were developed, a tool for retrobiosynthesis, and a computer-aided design platform for metabolic engineering, were developed, tested, and applied to a selection of synthesis/degradation challenges of industrial interest; resulting in the design of metabolic networks for biofuel production, CO2 deposition, and degradation of xenobiotics, which are potential starting points for subsequent metabolic engineering projects.

In WP6, we developed a portal, making Microme data freely available to the scientific community. The Microme portal enables the visualisation of pathways and their variants, a clear representation of pathway data and its links to the underlying literature, small molecule, protein, reaction databases; and the ability to visualise the taxonomic spread of projected pathways across the complete range of microbial genomes. New query engines allow for the selection, visualisation and download of Microme data. Access is also provided to all tools and data sets developed during the project; while a set of web services (implemented using the standard REST-ful paradigm) provide computational access to the data developed by the Microme partners. All Microme data is accessible for view or download without restriction.

WP7 was dedicated to training and outreach. In the early part of the project, training was mainly focused on internal project partners, identified collaborators, and scientists with an interest in participating in the curation process on selected species or pathways, and introducing them to data, analysis tools and curation software useful in this process. These training sessions were coordinated closely with WP2 activities and curation goals, and expanded on a successful training programme for microbial genome annotators in operation at Genoscope; and were associated with a three curation jamborees which brought together partners and other interested members of the community to target data in selected key areas for priority integration. Finally, the project concluded with an open 2-day training workshop hosted at EBI, in which participants from many project partners jointly taught the Microme tools and related tools and databases to an audience comprising 23 researchers from 9 European countries.

Management and internal coordination activities were conducted within WP8.

The project is acknowledged in 111 scientific publications. All public deliverables are available on the Microme project portal (http://www.microme.eu/deliverables) and disseminated through workshops and conferences.

In summary, the major achievements of the project were as follows:

The development of a new suite of tools for the management and analysis of bacterial genomic and metabolic data (work package 1, D1.1 D1.2 D1.3).

The implementation for tools to integrate and infer the presence of reaction catalysts in genomic sequence, and to project the presence of metabolic pathways into newly sequenced genomes (D1.4 D1.6 D1.8 D1.9).

Software for checking the chemical and stoichiometric consistency of reactions (D1.5).

The development of new text mining software, TaBactEn, for automatic retrieval of literature support for projected pathways (D1.7).

The regular release of Microme data, cumulating in the 4th major release of data at the termination of the project (WP2). The final release comprised over 8,000,000 gene-reaction associations derived from over 9,000 genomes, with additional reactions added in the final release through the addition of a new gap filling mechanism (see table 1, below). In addition, 30 taxonomically diverse genomes were identified at the start of the project for priority attention for curation curation and model building. For these genomes, the goal was to generate a species-specific pathway assembly: a set of all pathways and variants recorded in a genome through a combination of automatic methods and manual curation. This has been done as genome sequence has become available, suing the MicroScope platform. 19 SSPAs have been produced (see table 2, below), have been represented in BioPax file format, and are available for download, as part of the version 4.0 data release. The full data is available for download on the Microme FTP site at ftp://ftp.ebi.ac.uk/pub/databases/microme/releases
The development of a public resource for biological facts (D3.3) integrated with a set of tools for model construction and testing, publicly available at http://microme.systemsbiology.nl.

The development of software for the generation and validation of metabolic models, resulting in the release of 30 tested models at the end of the project (D3.1 D3.2 D3.4 D3.5 D3.6 D3.7).

The development of software for inference of ancestral metabolic components (D4.9),. First, a list of reference genomes using the target Microme species were defined, connected by an evolutionary tree. Second, a list of reactions or Microme pathways were used as queries to search against the reference genomes. Third, a sequence comparison was carried out using enzyme protein sequences from the reactions/pathways against the full reference genomes. Fourth, a fast parsimony algorithm was executed that assessed the presence or absence of reactions and thus pathways in the target species along the evolutionary tree. Finally, a Cytoscape software plugin was used to visualize the results and help users navigate the tree of species for the presence/absence of specific reactions/pathways.

The development of software for genomic context analysis (D4.10) and for genome-scale comparison of metabolic spaces (D4.11).

The development of software for retro-biosynthesis (D5.2).

The development of a computer-aided design program for bio-transformations and biodegradation (D5.3) enabling users to search for new pathways of biotechnological interest.

Proposals of constraints for use in retrobiosynthesis (D5.4).

Proposal of metabolic networks for use in metabolic engineering (D5.5). For example, Terephtalic acid is a commodity chemical, that enters the production of several materials produced in very large amounts, such as PolyEthylene Terephtalate (PET, >30 million tons in 2011), but also other polyester of industrial or engineering relevance. The production processes available to the industry are however complicated by the limited purity levels achievable at certain steps, resulting in the need to separate undesired side products, and the requirement of strong solvents. The proposed biosynthesis pathway permits the conversion of glucose into terephtalic acid.

Development of a public web portal (D6.1) providing data access (D6.2) and associated query tools (D6.3 D6.5 D6.6) with associated web services (D6.5).

The organisation of 3 annotation jamborees (D7.1 D7.3 D7.5) and 3 training courses (D7.2 D7.4 D7.6).

Contribution to 111 scientific publications.


Table 1. Comparison of the Microme Data releases 3.0 and 4.0. (see attachments)

Table 2. Genomes for which SSPAs have been included in Microme data release 4.0. (Models have been generated for all these Species – see D3.7)

Potential Impact:
The Microme project has made available to the scientific community an integrated collection of information resources, namely, a curated repository of reference microbial pathways; pathway assemblies for a large set of bacterial genomes; and constraint-based metabolic models based on these assemblies. Based on a solid software infrastructure and a rich conceptual framework, Microme (i) enabled the establishment of a bi-directional information flow, from genome annotation to metabolic simulation, and vice versa, adding thereby a new dimension to genome annotation; (ii) opened new avenues in research in evolutionary and biotechnological problems; and iii) provided a solid foundation for advances in green and white biotechnology.

1.4.1. Potential impact

The future of human kind depends on making more efficient, more sustainable, less polluting use of available raw materials and energy. The exploitation of biological catalysts, which have evolved to enable species to affect transformations necessary for their survival and deal with deficiencies in nutrients and energy, and with toxic environments, appears to be among the most promising routes to ensuring our own future prosperity. Microbial catalysts are especially interesting; firstly, there is enormous, and still mostly unchartered, microbial diversity; secondly, microbial species have adapted to some of the most extreme environments on the planet, presumably through metabolic adaptations; thirdly, microbial organisms may be more manipulable in the laboratory than higher organisms; and fourthly, the small size of microbial genomes allows for their rapid, low cost determination, enabling the potential establishment of a catalogue of all microbial genes as a toolset for bio-engineers tacking problems in domains including energy, pollution and food.
The value of this toolset is dependent on the quality of functional annotation; to understand the usefulness of a gene to ourselves, we first need to know what it does in the microbe. In the cases of novel enzymatic function, this may need to be determined experimentally; although in other cases, it may be inferred. As the cost of genome sequencing falls (and thus the availability of genome sequence increases), there is a vital need to extend the range and depth of such inference; firstly, to ensure that everything that can already be known is duly identified and catalogued; and secondly, because the near-completion of metabolic networks and the study of the resulting gaps should lead to the discovery of hitherto unknown catalytic mechanisms. The successful implementation of the Microme project will ensure that genome sequencing leads to rapid discovery of novel catalytic activities; and facilitate the development of biotechnological solutions to many of the world’s most important problems.
The development of high throughout genome sequencing technologies has enormous potential to increase our understanding of basic biology and to develop biotechnological applications. However, genome sequence alone does not tell us how an organism responds to its environment, or and what catalytic activities is uses (and in which combination) to do so. Microme developed both a data set and a tool set to address these questions, tested in the context of specific in vivo and in silico experimental data generated in the course of the project. The outputs have been an infrastructure for the integrated storage, analysis and dissemination of molecular, pathway and genome data, integrated with other reference resources and capable of scaling to thousands of genome sequences; a set of novel methodologies exploiting the existence of data from many species for the understanding of individual species or biological problems, utilising systems biology and evolutionary approaches; and a set of tools for the application of this knowledge for the design of biosynthetic strategies capable of utilising the natural repertoire of chemical transformations for applications in green and white biotechnology along the lines of the Knowledge-Based Bio-Economy (KBBE).
In this context, Microme has:

• Developed a computational resource dedicated to the recognition of enzymatic activities in microbial genomes and to the identification of novel sets of biochemical transformations.
• Focused on reactions behind production of valuable chemicals and environmentally significant processes (e.g. alternative energies, nutrient cycles, green chemistry).
• Identified new pathways for biodegradation of recalcitrant and xenobiotic molecules.
• Provided a framework with which to explore the metabolic space of microorganisms and microbial communities for potential applications of biotechnological interest.
• Pin-pointed orthogonal and ancestral metabolic modules and their possible intertwining in novel combinations of potential relevance

What is the connection of such items for KBBE? The answer is metabolic engineering. This umbrella concept is about rational modification or optimization of genetic, metabolic and regulatory processes aimed at improving given biocatalytic processes in terms of (i) enhancing the productivity and yield, (ii) eliminating by-products, (iii) reducing the energy consumption, and (iv) extending the substrate range. One prerequisite for an applicable metabolic engineering is the access to a thorough and comprehensive knowledge of metabolic pathways, and a modelling framework that enables the systematic assessment of biochemical capabilities and their underlying metabolic networks. The Microme project provides a solid and flexible resource that contains all the information necessary for a better understanding of biochemical reactions and how they can be refactored for an optimal application.
Microme and Synthetic Biology
One basic notion behind Synthetic Biology is that a biological system can be seen as a complex combination of functional, stand-alone elements not unlike those found in man-made devices, and can thus be deconstructed in a limited number of components and reconstructed in an entirely different configuration for the sake of modifying existing properties or creating altogether new ones. The diversity of pathways and enzymes amenable to applications in White and Environmental Biotech does not stop in those that occur naturally. Novel enzymatic specificities and activities can be designed and evolved in the Laboratory thus allowing the design of metabolic routes with no natural equivalents, including those that act on non physiological substrates. In this way, metabolic intermediates with no natural counterparts are rationally implemented in bioproduction hosts so as to give access to commodity and fine organic chemicals for the industry. A particular emphasis is put on constructing metabolic cycles for fixing carbon dioxide, carbon monoxide and formaldehyde departing from pathways known in natural autotrophs and methylotrophs. Such novel pathways could significantly impact on both diversification of organic reactions and sequestration of carbon oxides at an industrial scale following this conceptual frame.
To achieve this objective Microme addressed the modularization and orthogonalization of metabolic blocks. As mentioned above, a prerequisite for robust engineering of new biological functions, including metabolic functions, is the need that the components of the design operate in a context-free fashion. In the real word, however, this behaviour is most often not achieved. On the contrary, naturally occurring metabolic modules, even the simplest, are connected to other modules or unavoidably linked to growth functions. For improved metabolic setups ambitioned to perform beyond the very limited conditions of the Laboratory, this certainty cannot be ignored. The metabolic output of most natural, multi-step reactions is not usable for robust circuit design in live bacteria. Although it is indeed possible to force microorganisms to run a reaction that they do not normally do (as Biotechnology has been doing for 40 years), the issue at stake is whether such artificial scenarios are sufficiently stable in the long run or whether they relapse into an undesired metabolic connectivity as soon as they are exposed to Darwinian selection for enough time. Evolutionary adaptation of bacteria, even in a small period, recurrently results in more complex and/or more-interdependent systems, a very undesirable scenario for engineering. To address this issue, Microme pursued the reconstruction of ancestral metabolic modules as a way to generate pre-evolved and pre-connected pathways endowed with a lesser degree of dependency and thus more suitable for directed design of new catalytic processes. Microme addressed the identification of such earlier modules and facilitated their re-creation by genetically de-branching existing pathways or reprogramming altogether new ones via DNA synthesis of the genes involved.


1.4.2. Main dissemination activities and exploitation of results


Dissemination activities

Because this proposal has been framed as an effort to produce enabling infrastructures, the bulk of the results were made available to the general scientific and technical community. The Beneficiaries produced since December 2009 111 scientific publications acknowledging Microme’s funding in international journals, as well as contributions to more than 100 international meetings. By providing a successful scientific basis for industrial activities in the European Union, the laboratories have certainly become more attractive to European industries for future co-operation.
Besides the standard channels for publicity of scientific results (e.g. publications in international refereed journals, presentations in international meetings and the like), Microme also assisted, through the various functions of the PIs involved within the consortium, the circulation of data to key target groups such as industry, academia and the general public.

The Microme portal (developed in WP6) includes web, web-service and FTP-based interfaces, providing free public access to the pathways and models, and providing interfaces to the set of analysis software developed in WP 1-5.


Exploitation activities

The project beneficiaries monitored and prospected permanently for possible exploitation of the technologies emerging from the work. Four exploitable foregrounds were identified at the end of the project: 1) Degradation of S-alkyl-cysteine compounds, with entirely novel metabolic pathways; 2) two pathways of industrial interest for the production of terephtalic acid; 3) two pathways of industrial interest for the production of acrylic acid; and 4) TeBactEn (Text mining for Bacterial Enzymes): a text mining application for retrieval, extraction and annotation of bacterial enzymatic reactions and pathways from the literature.
List of Websites:
The project website has the address: www.microme.eu

Contractors involved

European Molecular Biology Laboratory (EBI): Paul Kersey
Centre for Research and Technology Hellas (CERTH): Christos Ouzounis
Commissariat a l’Energie Atomique (CEA): Claudine Médigue
Agencia Estatal Consejo Superior de Investigaciones Cientificas (CNB): Victor de Lorenzo
Fundacion Centro National de Investigaciones Oncologicas Carlos III (CNIO): Alfonso Valencia
Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ): Hans-Peter Klenk
Isthmus: Philippe Marlière
Wageningen University (WUR): Vitor Martins dos Santos
Molecular Networks GmbH (MN): Johann Gasteiger
Swiss Institute of Bioinformatics (SIB): Ioannis Xenarios
Université Libre de Bruxelles (ULB): Jacques van Helden
Genome Research Limited (WTSI): Julian Parkhill
Tel Aviv University (TAU): Eytan Ruppin
Amabiotics (AMB): Antoine Danchin

Coordinator contact details

Consortium director: Paul Kersey
Consortium manager: Pascal Kahlem
EMBL - European Bioinformatics Institute
Wellcome Trust Genome Campus
Hinxton, Cambridge CB10 1SD
United Kingdom
Tel: +44 (0)1223 494 601
Email: pkersey@ebi.ac.uk