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View on the different efforts to enable, develop and implement a common systems biology infrastructure for Europe

Susanne Hollmann, Babette Regierer

As reported in the last issue of Systembiologie.de in November 2012 a first "community building" meeting for bioinformatics and systems biology issues was carried out in Amsterdam with the participation of more than 25 researchers and coordinators of various life science EU initiatives as well as COST Actions. Background of the two-day meeting initiated by the EU Coordination Action "ALLBIO Broadening the Bioinformatics Infrastructure to Unicellular, Animal and Plant Science" was to discuss the current challenges in bioinformatics and the activities to be addressed in the future. In this context, it was of high importance to identify other areas of development and activities in computational biology and to find important interfaces and not yet existing links between these initiatives. For that reason, all participants have been invited to shortly represent their projects and initiatives. It became apparent that most of the represented initiatives have a very tight link to each other in the areas of data standardization, training and education especially in the field of computational biology. Significant areas identified are the management and integration of biological data, sequence analysis, computational biology approaches, and analysis of data from high-throughput technologies.

To analyze data on a large scale is an essential pillar of Systems Biology. Thus computational biology and systems biology are closely interrelated. As a first important result of this meeting and an issue that needs further attention is the bundling and the interaction of existing initiatives in the areas of data standardization, training and education in systems biology/life science.

Especially systems biology approaches require the availability, co-ordination and simultaneous interaction of a large number of diverse facilities and activities. These range from mathematical and formal modelling to biological, biomedical and clinical experiments, to targeted technology development.

For each medical, biological or biotechnological problem to be addressed, the optimal combination of facilities and activities is likely to be specific and individual. Due to the complexity of biological systems and the fact that the total spectrum of activities is large and dynamic, their analysis cannot be undertaken by a single country or entity. Based on the opportunities offered by national and European funding programs a huge variety of excellent initiatives and projects could be set to live over the years that all contribute to the current paradigm shift in modern life sciences and prepared the ground for the understanding of the fundamental aspects of life via systems biology.

However, the vision and demand of the initiatives where contact is already made via the previous activities can be comprised as: To provide the European systems biology community access to an infrastructure with fast and tailor-made experimental and computational solutions for systems biology, systems medicine and biotechnology.

The systems approach to tackle the complexity of life that has emerged relatively recently provides a profound conceptual advance compared to the biological research of the past. In order to address this aim and support systems biology across whole Europe, a distributed, but closely interconnected infrastructure will be established. This will help to facilitate the synergistic application of a wide range of research techniques and technologies to problems of major medical and biotechnological importance: The Infrastructure for Systems Biology in Europe (ISBE) – as part of the ESFRI process.

Rather than focussing on individual laboratories specialising in a limited number of research technologies, ISBE will interconnect so called hubs of technological excellence in Systems Biology, offering the best European research expertise, and experimental as well as modelling facilities, necessary for systems biology.

ISBE will establish and make available repositories of data and models, and enable real-time connections within and between experimental and modelling facilities. External user laboratories will be connected efficiently by provision of connections to existing high capacity electronic network infrastructures. Thus, the ISBE programme aims at the establishment of a network infrastructure that is designed to meet the needs of European Systems Biology in terms of development, application and training. The ISBE infrastructure will also gather and facilitate efficient interaction with the substantial technology development efforts relevant to Systems Biology already funded by national and EU programmes.

Where relevant assays or modelling experiments cannot be performed locally, ISBE will enable European laboratories to model, conduct experiments and undertake other essential activities remotely by means of the planned interconnected centres:

  • DICs will be research centres that apply and develop expertise in model-driven data integration and make this expertise available to the community.
  • DGCs will be technology-based centres that allow the access to a wide range of high, medium and low throughput technologies that are essential for the acquisition of quantitative datasets under standardised conditions.
  • DSCs will be centres that are responsible for data processing, curation and analysis – they store data, models and simulations.

ISBE started as a bottom-up initiative from the scientific community and is funded as an ESFRI initiative since August 2012 supported by 23 partners from 11 European countries (http://www.isbe.eu; contact: R. Kitney, UK). ISBE is connecting and linking to other national or European initiatives in the life sciences because of the broad scope of systems biology. Close links are in the field of systems biology, systems medicine or to projects in synthetic biology as well as in bioinformatics. In many cases, these projects started as independent initiatives; with the establishment of ISBE will be the unique chance to create strong links between the different aspects and leverage the potential of the existing interfaces. Via a targeted communication strategy and an efficient flow of information between the projects, initiatives and networks, a huge critical mass covering all thematic aspects will be generated for the benefit for the life science in Europe at large

Some initiatives have a very tight link to ISBE, especially in the areas of data standardization and training in systems biology. Some of the initiatives which interact already actively with ISBE will be introduced shortly here. The initiatives and projects mentioned here are only small selections of the variety of initiatives that exist within Europe. The connections between existing initiatives still need to grow and need to be intensified. The importance to link and use the opportunities that emerge from the interaction is perceived as a general added value. Other initiatives are therefore invited to get in contact to exchange information and to elucidate potential synergies and meaningful collaboration.

Initiatives on data standardization and on training and education in the life sciences have an already identified substantial interface to ISBE. Among these initiatives are:

AllBio: Broadening the Bioinformatics Infrastructure to unicellular, animal, and plant science

Contact: Dr. Erik Bongcam-Rudloff, Swedish University of Agricultural Sciences (SE)

The completion of the human genome sequence has triggered worldwide bioinformatics efforts to unravel its information content. These projects have produced large numbers of novel analytic and predictive computer programs. The majority of these developments have focused on the human genome, transcriptome, proteome, epigenome, etc., and less effort has been invested in other genomes in life science research fields related to unicellular organisms, plants, or animals.  One central aim of the project is to transfer the knowledge of existing bioinformatics tools and web services among the various life science areas and to identify still unsolved bioinformatics challenges. There are many different-yet-similar activities in the field of bioinformatics, both in Europe as well as worldwide. Previous work in AllBio revealed bioinformatics challenges and needs, among them standardization was one of the major issues of interest. www.allbioinformatics.eu

CASyM: Coordinating Action Systems Medicine

Contact: Marc Kirschner, Forschungszentrum Jülich, Projektträger Jülich (DE)

CASyM is a European consortium, functioning as a strategic managing and coordinating platform, that joined forces to develop a road map outlining an integrative approach for the implementation of Systems Medicine across Europe. CASyM is supported by the FP7- Directorate-General for Research and Innovation of the European Commission and combines extensive experience from its twenty-two partners, including research, higher education and health care organizations, SMEs and pharmaceutical companies, funding bodies as well as research clusters and project management agencies. CASyM is about all aspects of medicine, and emphasizing clinical medicine, from clinical trials through public health and data handling, to application of Systems Medicine and medical economics. During the next four years, CASyM will assess the basis for a European Systems Medicine paradigm and will assist the medical community in creating the foundation for a new perspective by focusing on an approach based on personalized, predictive, preventive and participatory (4P) medicine. www.casym.eu

ERASysAPP -  ERA-Net for Systems Biology Applications

Contact: Klaus-Peter Michel, Forschungszentrum Jülich, Projektträger Jülich (DE)

ERASysAPP has been launched in January 2013 as a novel Europe-wide initiative to coordinate and enhance research opportunities in the emerging scientific field of Systems Biology. This novel ERA-Net for Applied Systems Biology is the successor of the former successful ERA-Net ERASysBIO and its spin-offs ERASysBIO+, SysMO and SysMO2. To strengthen the applied aspect of systems biology, 16 funding agencies from 13 European countries joined forces through the ERA-Net. ERASysAPP predominantly aims at funding transnational applied Systems Biology research, encouraging institutions and scientists from different countries, EU Member States as well as others, to network and share existing resources, especially for data management and training. The future joint transnational translational SB ERASysAPP calls will be executed on a variable geometry basis - meaning that each partner country participating in the respective call will define participation and net funding contribution prior to the launch of a call. The first call will be launched in November 2013 and is thematically and organisms-wise open to the best fetch the most excellent ideas in the community on Systems Biology. http://www.erasysapp.eu.

GOBLET – The Global Organisation for Bioinformatics Learning, Education & Training

Contact: Carole Goble, University of Manchester (UK)

High-throughput biology, especially NGS, is generating vast quantities of complex data that require detailed and accurate analysis. This presents enormous challenges to bioscience researchers, demanding new levels of biomathematical and computational know-how. Nevertheless, bioinformatics and biostatistical skills are in short supply. The need to up-skill practising bioscientists, and to continue training professional bioinformaticians, is urgent; yet the provision of bespoke courses and specialist workshops has generally been disjointed and poorly funded. GOBLET aims to address these issues by providing a coherent solution at the global level, offering a platform via which to disseminate programmes of learning to bioscientists across the complete bioinformatics landscape. To date, 24 international organisations have joined GOBLET: their mission, to provide a global, sustainable support structure for bioinformatics trainers and trainees, and facilitate capacity development in bioinformatics in all countries. www.mygoblet.org

ELIXIR - European life science infrastructure for biological information

Contact: Janet Thornton, EMBL-EBI (UK)

ELIXIR unites Europe’s leading life science organisations in managing and safeguarding the massive amounts of data being generated every day by publicly funded research. It is a pan-European research infrastructure for biological information. ELIXIR will provide the facilities necessary for life science researchers - from bench biologists to cheminformaticians - to make the most of our rapidly growing store of information about organisms, which is the foundation on which our understanding of life is built. The collection, curation, storage, archiving, integration and deployment of biomolecular data is an immense challenge that cannot be handled by a single organisation or by one country alone, but requires international coordination. ELIXIR builds on existing data resources and services. It follows a hub-and-nodes model, with a single hub located in a new building that will be based at EMBL-EBI in Hinxton, UK and a growing number of nodes located at centres of excellence throughout Europe. The goal of this distributed structure is to ensure that data are kept safe and made easily accessible. ELIXIR co-ordinates also the BioMedBridges project, which is a key initiative to bring together the ESFRI Research Infrastructures in the Bio Medical Sciences field. Via the project a shared e-infrastructure - the technical bridges – will be developed to allow interoperability between data and services in the biological, medical, translational and clinical domains and thus strengthen biomedical resources in Europe. www.elixir-europe.org

SysMO-DB - For finding, sharing and exchanging Data, Models and Processes in Systems Biology.

Contact: Carole Goble, University of Manchester (UK) / Wolfgang Müller, Heidelberg Institute for Theoretical Studies (DE)

SysMO-DB is a project that is creating a web-based platform, and tooling, for finding, sharing and exchanging Data, Models and Processes in Systems Biology. It was designed to support the SysMO Consortium (Systems Biology for Micro-Organisms), but the principles and methods employed are equally applicable to other multi-site Systems Biology projects.The main objectives of SysMO-DB are to: facilitate the web-based exchange of data between research groups within the consortium and with other consortia, and to provide an integrated platform for the dissemination of the results of the SysMO projects to the scientific community. SysMO-DB follows several key principles: i) exploit what is already available, from the consortium and from the wider scientific community, and avoid reinvention; ii) identify the least we can do to make a benefit and do this incrementally. www.sysmo-db.org

EraSynBio - ERA-NET for the development and coordination of Synthetic Biology in the European Research Area

Contact: Dr. Annette Kremser, PTJ (on behalf of BMBF, DE)

ERASynBio is a three-year programme funded under the European Commission ERA-NET scheme (Contract number: 291728) in the 7th Framework Programme. The objective of the ERA-NET scheme is to step up the cooperation and coordination of research and development activities carried out in the Member States and Associated States. ERASynBio brings together 16 funding and/or management organisations from 14 countries and two observer countries with important activities in the field of Synthetic Biology, aiming at coordinating national and regional funding programmes in the field of Synthetic Biology. www.erasynbio.eu

SystemsX.ch – The Swiss Initiative in Systems Biology

Contact: Daniel Vonder Mühll, SystemsX (CH)

SystemsX.ch is the largest ever public research initiative in Switzerland and focuses on a broad topical area of basic research. The initiative advances systems biology in Switzerland with the claim of belonging to the best in the world in this area of research. SystemsX.ch currently comprises twelve equal partner institutions and supports over 1000 scientists and some 300 research groups working on more than 100 projects. Different project types are supported: The Research, Technology and Development (RTD) Projects are the flagship projects of SystemsX.ch. Since the beginning of the initiative, approximately 107 million Swiss francs have been invested in these interdisciplinary and inter-institutional research projects. One of SystemsX.ch's main tasks includes the promotion and training of future systems biologists: With the Interdisciplinary PhD Projects (IPhD) and the Transition Postdoc Fellowships (TPdF) the initiative specifically promotes young scientists and students. The Transfer Projects encourage cooperation and bridge the gap between universities and the private sector (industry, SMEs, spin-offs and hospitals). www.systemsx.ch

COMBINE - COmputational Modeling in BIology Network

The 'COmputational Modeling in BIology Network’ (COMBINE) is an initiative to coordinate the development of the various community standards and formats for computational modeling, initially in Systems Biology and related fields (http://co.mbine.org/). The aim is to create a common platform for allied standardization efforts in the field and connect the different communities together. By doing so, it is expected that the federated projects will develop a set of interoperable and non-overlapping standards covering all aspects of modeling in biology. The core set of COMBINE standards currently comprises BioPAX (Biological Pathway Exchange format), the Systems Biology Graphical Notation (SBGN), the Systems Biology Markup Language (SBML), the Simulation Experiment Description Markup Language (SED-ML) and CellML. However, there also other associated standardization efforts that are connected to COMBINE. Building on the experience of mature projects, which already have stable specifications, software support, user-base and community governance, COMBINE will help foster or support fledging efforts aimed at filling gaps or new needs. www.mbine.org

The future success of the European economy will depend strongly on our ability to enhance existing (and develop new) knowledge-based industries. Thus, we arrive at the conclusion that the ISBE infrastructure in a joint effort with other projects and initiatives will impact European industry, business and society through the systematic study of complex biological processes and by incorporating in this approach expertise derived from the physical sciences, engineering, biology, computer science and mathematics. This will lead to new and important technological applications; for example, in health, agriculture, food production, clean energy and other areas related to the growing bio-based economy of Europe. Specifically, systems biology will transform our basic knowledge of complex molecular systems into the new area of predictive, preventive, personalised and participatory medicine. The systems biology approaches developed on the ISBE infrastructure will provide new insights and assist the development of tools for the design of new biotechnological and environmental applications. ISBE will also transform systems biology into an integrated, pan-European activity by linking all expertise needed, by the use of web-based experimental facilities and on-line mathematical modelling. ISBE will make the biological sciences more productive and cost-effective. This is important for European science, society, industry and business in nearly all areas of modern life.

In conclusion, ISBE in combination with all the other national and Euopean initiatives demonstrate that the grand challenges that we face require international coordination and cooperation to generate the best possible impact for the European life science community.