Systems biology is an emergent field that aims at system-level understanding of biological systems. Since the days of Weiner, system-level understanding has been a long standing goal of biological sciences. Cybernetics, for example, aims at describing animals and machines from the control and communication theory. Unfortunately, molecular biology has just started at that time, so that only phenomenological analysis has been possible. It was only recently that system-level analysis can be grounded on discoveries at molecular-level. With the progress of genome sequence project and range of other molecular biology project that accumulate in-depth knowledge of molecular nature of biological system, we are now at the stage to seriously look into possibility of system-level understanding solidly grounded on molecular-level understanding.
What does it mean to understand at "system level"? Unlike molecular biology which focus on molecules, such as sequence of nucleotide acids and proteins, systems biology focus on systems that are composed of molecular components. Although systems are composed of matters, the essence of system lies in dynamics and it cannot be described merely by enumerating components of the system. At the same time, it is misleading to believe that only system structure, such as network topologies, is important without paying sufficient attention to diversities and functionalities of components. Both structure of the system and components plays indispensable role forming symbiotic state of the system as a whole.
Within this context, (1) understanding of structure of the system, such as gene regulatory and biochemical networks, as well as physical structures, (2) understanding of dynamics of the system, both quantitative and qualitative analysis as well as construction of theory/model with powerful prediction capability, (3) understanding of control methods of the system, and (4) understanding of design methods of the system, are key milestones to judge how much we understand the system.
There are numbers of exciting and profound issues that are actively investigated, such as robustness of biological systems, network structures and dynamics, and applications to drug discovery. Systems biology is in its infancy, but this is the area that has to be explored and the area that we believe to be the main stream in biological sciences in this century.
References:
H. Kitano, Systems Biology: a brief overview, Science, 295:1662-1664, 2002
H. Kitano, Computational Systems Biology, Nature, 420:206-210, 2002
Towards a European Research Area for Systems Biology
A transnational funding initiative to support the convergence of life sciences
with information technology & systems science
with information technology & systems science
The ERASysBio Coordination Action springs from a Specific Support Action (SSA) that has already laid the foundations of this new network. It brings together funding agencies from 13 countries including Israel and Russia. Associate partners Luxembourg and Switzerland are expected to join later. It will build not only on national programmes in systems biology but also upon several European efforts springing from EUREKA, the European Science Foundation, the European Molecular Biology Laboratory and several other EU-supported projects.
Agenda for research
The first step will be to collect information about the projects and programmes under way in the 12 partner countries and their plans for the future. Next, the partners will draft a research agenda in systems biology for the period 2006-2008 outlining topics of common interest and potential for future collaboration. Once an agreed agenda is in place, the partners will start to pave the way for new transnational funding initiatives by setting up the appropriate contractual arrangements and a joint funding scheme. A web-based service to help students and researchers set up exchanges will be provided through the existing European Researchers Mobility Portal. A public information campaign will be developed at the same time. Finally, the project will manage, with national agencies, two series of synchronised funding rounds. A pilot one on the systems biology of micro-organisms has already been launched at the end of 2005. A further one will focus on topics yet to be decided. Networking will be promoted by partnering and brokerage events. By the end of the three-year ERASysBio several research projects should be under way.
Systems biology will have obvious applications in medicine, such as in the rational design of pharmaceuticals, especially those involving several different molecular targets. It will also help in the development of drugs specific to small groups of people or even individuals, made possible by new insights from genome research. Outside medicine, systems biology is likely to have a big impact on agriculture and biotechnology and is expected to be a major contributor to Europe’s industrial future.
Research field:
Computational biology; systems engineering; informatics; mathematics
Databases, Tools and Simulations
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BioCyc - "BioCyc is a collection of Pathway/Genome Databases. Each database in the BioCyc collection describes the genome and metabolic pathways of a single organism, with the exception of the MetaCyc database, which is a reference source on metabolic pathways from many organisms."
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Database of Interacting Proteins (DIP) - A catalog of experimentally determined protein-protein interactions and related projects like the Database of Ligand-Receptor Partners (DLRP), LiveDIP and the Java-based JDIP. (David Eisenberg, University of California, Los Angeles)
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Database of Quantitative Cellular Signaling - "The Database of Quantitative Cellular Signaling is a repository of models of signaling pathways." (National Centre for Biological Science, India)
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Endomesoderm Gene Network - A genomic view of the regulatory gene network for endomesoderm specification (Davidson Lab, California Institute of Technology)
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Kyoto Encyclopedia of Genes and Genomes (KEGG) - Graphical and hypertext-based information on biochemical pathways, including metabolic and regulatory pathways (for instance, cell cycle and growth factor signaling).
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PathBlast - Tool for aligning two protein interaction networks to elucidate conserved pathways.
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SiC: The Silicon Cells - Computer simulations of biochemical networks in specific cells based on experimentally determined rate laws and parameter values.
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Virtual Cell - "The National Resource for Cell Analysis and Modeling, NRCAM, has created a remote user modeling and simulation environment where users can create biological models of various types and run simulations." (University of Connecticut Health Center)
See also the Scientific Databases and Tools page for genomics and proteomics databases and the Metabolic Pathway Databases and Signal Transduction Databases sections of the relevant pages.
Specialized Software and Computer Languages
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BioTapestry Editor - A Java-based "interactive tool for building, visualizing, and simulating genetic regulatory networks." (Bolouri Group, Institute for Systems Biology, Davidson Lab, California Institute of Technology)
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CellDesigner - A "a modeling tool of biochemical networks with graphical user interface. It is designed to be SBW (Systems Biology Workbench) compliant, and support SBML (Systems Biology Markup Language) format."
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Cell Markup Language (CellML) - An XML markup language which, along with MathML and RDF, "will provide a complete vocabulary for describing biological information at a range of resolutions from the subcellular to organism level."
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Cytoscape - "[O]pen source bioinformatics software platform for visualizing molecular interaction networks and integrating these interactions with gene expression profiles and other state data."
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E-CELL Project - "[I]nternational research project aiming to model and reconstruct biological phenomena in silico, and developing necessary theoretical supports, technologies and software platforms to allow precise whole cell simulation." (Institute for Advanced Biosciences, Keio University, Japan)
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Gene Ontology Consortium - "The goal of the Gene OntologyTM (GO) Consortium is to produce a controlled vocabulary that can be applied to all organisms even as knowledge of gene and protein roles in cells is accumulating and changing."
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Languages for Systems Biology (Luca Cardelli, Microsoft Research Cambridge, UK)
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Open Biological Ontologies - "[U]mbrella web address for well-structured controlled vocabularies for shared use across different biological domains."
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Pathway Hunter Tool - Metabolic pathway analysis web service, including shortest, alternate path, Load points, Choke points and network analysis. (Cologne University Bioinformatics Center, Germany)
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PathwayLab - A commercial software tool for modeling, computational analysis and information management of biochemical pathways. (InNetics)
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Systems Biology Toolbox 2 (SBtoolbox2) for MATLAB - A modeling, simulation and analysis tool for biochemical systems. (Henning Schmidt, University of Rostock, Germany)
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Software and Databases for Computational Biology on the Internet (Steven Salzberg, Johns Hopkins University)
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Systems Biology Markup Language (SBML) - A "computer-readable format for representing models of biochemical reaction networks. SBML is applicable to metabolic networks, cell-signaling pathways, regulatory networks, and many others."
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Systems Biology Workbench (SBW) - A "modular, broker-based, message-passing framework for communication between applications that aid in research in systems biology."
See also the Scientific Software page.
Nucleic Acid, Gene and Genomics Databases
Protein and Proteomics Databases
Metabolic Pathway Databases (Data Collections on Metabolic Pathways)
Signal Transduction Databases (Data Collections on Regulatory Pathways)
Discussion Groups
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BioChemWeb.org Discussion Board - Discussions and questions/answers for scientists and students.
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Usenet newsgroup archives from BIOSCI/bionet (can also be accessed through Google Groups: bionet):
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BIOLOGICAL-INFORMATION-THEORY/bionet.information-theory - Biological information theory.
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BIOMATRX/bionet.molbio.bio-matrix - Computer applications to biological databases.
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COMPUTATIONAL-BIOLOGY/bionet.biology.computational - Computer and mathematical applications
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