The CoCoMac project in the context of European neuroinformatics initiatives

The importance of neuroinformatics to improve and organize the flow of increasing amounts of neuroscience data and to develop an adequate infrastructure is increasingly being recognized also in Europe. Current progress is made either through individual research grants (often in coordination with US groups) or in the course of national efforts to implement the recommendations of the Organization for Economic Cooperation and Development (OECD) Working Group on Neuroinformatics. The 6th Framework Programme of the European Union (EU) in its Life Science priority with the 3rd call in 2004 limits the opportunities largely to the subcellular level; therefore it will be important to broaden the spectrum for the 4th call in 2005. The overall picture of European activities reflects the diversity of preferences and funding among heterogeneous groups of scientists and nations. One specific topic where Europe has particular needs, expertise and opportunities is brain connectivity and the question why real brain networks are so enormously powerful and versatile in solving a multitude of complex problems. Such a project would address brain connectivity at all levels from neurons to large-scale systems, and from structural, functional as well as inferential points of view. In the context of connectivity, the CoCoMac project (Collations of Connectivity data on the Macaque brain) is an example of a mature database that provides access to primary data from the literature, processed connectivity data and extensive mapping information based on 390 publications with a focus on the cerebral cortex of adult macaques. Since the first steps in 1997 to collate data, constrain data representation and implement quality assessment the project has developed to provide interfaces for automated online query and XML-formatted output for further processing. Current work extends the database to subcortical structures, provides tools for visualization and analysis, and investigates links between structural and functional connectivity. Major future directions include interoperability with other data resources including ontologies and coordinate-based atlases, extensions to additional data modalities, such as receptor and microcircuitry data, and the application of connectivity data to computer simulations and systems analyses, particularly in the context of functional imaging data. 1. European Neuroinformatics initiatives Europe has a longstanding history of research in the field of neuroinformatics / computational neuroscience, although this field had different names and flavors in different European countries (see e.g. Kötter 1999). For about a decade we have seen initiatives on a European level mainly addressing issues of coordination, visibility, funding of workshops, scholarships and training programs. Among the best known of these initiatives is the EU Advanced Course in Computational Neuroscience, which started 1996 in Crete and has since moved on in a 34 triennial rhythm to Trieste, Obidos and Archachon. Other initiatives include the summer symposia supported by the European Science Foundation (ESF) and the Thematic Network “Computational Neuroscience and Neuroinformatics” funded by the 5th Framework Program of the European Union (see http://www.neuroinf.org). Much of the biomedical focus of the EU 6 Framework programme appears to have been inspired by the rise of biotechnology and the prospect of an ageing population. Combining these two thrusts it appeared feasible to use high-throughput genomic and proteomic approaches, which would allow us to identify and manipulate the factors that cause degenerative diseases of the various body systems including the brain. While an unprecedented flow of molecular data has provided many new and sometimes surprising findings it was almost ignored that other research approaches, for example in systems neuroscience, had considered the complexity of biological systems and developed methods suitable to analyze their organizational principles. Increasingly it is also being recognized that connecting the genomic and the behavioral level has to explicitly address also the cellular and systems levels, which were often short-circuited. In a recent issue on "systems biology" of Nature Biotechnology (Vol. 22, No. 10, October 2004) several authors lucidly recall the origin of this term and its re-definition in the context of genomics approaches and subcellular processing. The emergence of the “new” field of systems biology constitutes a paradigm shift for molecular biology, which had often focused on reductionist thinking. This should be a good message for the field of neuroinformatics / computational neuroscience since it is well equipped using computational approaches to study the complex systems without the need to re-invent itself as an extension of bioinformatics. The following is a list of current calls for project proposals in the priority 1: Life Sciences, Genomics and Biotechnology for Health to be funded by the European Union that have at least a vague relevance to neuroinformatics. LSH-2004-1.1. 0-2: Coordination Action (CA) proposals should aim at: developing a coherent strategy for the maintenance and sustainability of essential European database resources for all model organisms important in functional genomics research, or structuring systems biology research in Europe with particular emphasis on the collaboration between different expertises in life sciences research, or developing a European public-private partnership to solve current bottlenecks in the production of eukaryotic proteins in quantities and quality required by structural genomics and proteomics programmes, or improving European coordination of efforts to develop NMR methods for structural genomics, collaboration between human sample biobanks in epidemiological research. LSH-2004-1.1. 4-1: Development of a European-wide package for creating and integrating relevant databases and analysis software to enable systems-level interpretation of complex experimental data in functional genomic LSH-2004-2.1. 3-1: Neural molecular mechanisms of synaptic information processing LSH-2004-2.1. 3-5: Strengthening neuroscience research in Europe LSH-2004-2.1. 3-6: Workshop on neuroimaging in brain research LSH-2004-2.1. 3-7: Organisation of a workshop on databasing the brain LSH-2004-2.1. 3-8: Consensus document on future European brain research