| |
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Preface | |
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Acknowledgements | |
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| |
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Introduction | |
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Introduction | |
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Bioinformatics | |
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What Is Bioinformatics? | |
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References | |
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Trends in Bioinformatics | |
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What Is the State of the Art? | |
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The Role of Bioinformatics in Studying Health and Disease | |
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Bioinformatics Within Life Sciences Research Projects | |
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Types of Analysis | |
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Ontologies | |
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Genomics and Proteomics | |
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Structural Genomics | |
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Systems Biology | |
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What Is Systems Biology? | |
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References | |
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| |
Trends in Systems Biology | |
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| |
What Is the State of the Art? | |
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| |
Why Do Systems Biology? | |
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Approaches to Modelling | |
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Systems Biology Within Life Sciences Research Projects | |
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Research Areas for Analysis | |
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Dimensions of Life Sciences Research | |
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Choice of Area | |
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"Right-Size" Science | |
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Collaborative Research | |
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The Nature of Collaborative Research | |
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Advantages of Collaborative Research | |
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Access to Resources | |
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Research Paradigms | |
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European Commission Research Projects | |
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Framework Programmes | |
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Projects | |
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A Practical Guide to Project Websites, Participants, Coordinators, Publications | |
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Websites, Participants and Coordinators | |
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Project Publications | |
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Resources and Infrastructures | |
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Accessing Knowledge and Projects | |
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Participating in Projects | |
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Key Sources | |
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Fundamental Collaborative Research and Computational Biology | |
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Bioinformatics | |
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Introduction | |
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Genome Sequences | |
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| |
Annotation | |
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European Contributions | |
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Key Areas | |
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| |
Genome Annotation | |
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A European Virtual Institute for Annotation | |
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Distributed Annotation | |
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An Integrated Approach | |
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Annotation Deliverables | |
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Genome Browser and Distributed Annotation Viewer | |
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Experimental-Computational Collaboration | |
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Thematic Collaborations | |
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Critical Mass of Resources | |
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Bioinformatics Tools For Annotation | |
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Integrated Tool Development | |
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Integrated Layer for Genomic and Proteomic Data | |
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| |
Protein Structure | |
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| |
Expression Data | |
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Protein-Protein Interactions | |
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Protein Sequence and Function Database | |
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Protein Sequence Grouping | |
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Gene Definition/Alternative Transcripts and Splicing | |
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Gene Definition | |
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Gene Definition and Alternative Splicing Methods | |
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Alternative Transcription Goals | |
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Alternative Transcription Methods | |
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Future Research | |
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Gene Regulation and Expression | |
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Gene Regulation and Expression Processes | |
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DNA Microarray Data | |
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Expression Research Goals | |
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Gene Regulation Research Goals | |
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| |
Systems Biology of Transcription and Regulation | |
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| |
Functional Annotation of Proteins | |
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| |
Protein Sequence, Structure and Function Integration | |
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| |
Sequence to Structure to Function Results | |
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Functional Sites Results | |
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Small-Ligand Binding | |
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Future Plans | |
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Post-translation Modification, Membrane and Localisation Prediction | |
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Membrane Proteins and Results | |
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| |
Post-translation Modification and Localisation and Results | |
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| |
Future Post-translation Modification and Localisation | |
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| |
Protein Complexes, Networks and Pathways | |
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| |
Protein-Protein Complexes | |
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| |
Network Prediction | |
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| |
Metabolic Pathway Net | |
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| |
Future Pathway Work | |
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| |
Encyclopaedia of DNA Elements | |
| |
| |
Functional Elements in the Human Genome | |
| |
| |
International Collaboration | |
| |
| |
Functional Identification Methods | |
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| |
Genome Analysis Future | |
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| |
Major Result: Most DNA Is Transcribed to RNA | |
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| |
| |
Systems Biology | |
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| |
Introduction | |
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| |
Systems Biology Projects | |
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| |
Networks and Dynamics | |
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| |
Cell Cycle | |
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| |
Cell Cycle Regulation | |
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| |
Cell Cycle Ontology and Knowledge Warehouse | |
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| |
Cell Cycle Model Organisms | |
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| |
Cell Cycle Research Objectives | |
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| |
Systems Biology Data Generation | |
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| |
Cell Cycle and Health | |
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| |
Standard Cell Synchronisation | |
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| |
Periodically Regulated Genes | |
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| |
Functional Modules in the Cell Cycle | |
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| |
Data Visualisation and Analysis | |
| |
| |
P53 | |
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| |
The p53-Mdm2 Regulatory Network | |
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| |
Collaborative Approaches to Data Handling | |
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| |
Negative Feedback: p53 and Mdm2 Experiments | |
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| |
Negative Feedback: p53 and Mdm2 Modelling | |
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| |
Publications | |
| |
| |
Spindle Formation and Imaging | |
| |
| |
Light Microscopy | |
| |
| |
Microtubule Formation | |
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| |
Regulatory Feedback in Microtubule Formation | |
| |
| |
Signalling and Control | |
| |
| |
Central Role of Cell Signalling | |
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| |
Cell Growth, Differentiation and Survival Pathways | |
| |
| |
The Ras/Raf/Mek/ERK Pathway | |
| |
| |
Data and Modelling Interaction | |
| |
| |
Quantifying Signal Transduction | |
| |
| |
Mitogen-Activated Protein Kinase Pathways | |
| |
| |
AMP-Activated Protein Kinase Signalling Pathway | |
| |
| |
Health Applications of AMPK Modelling | |
| |
| |
Metabolic Regulation | |
| |
| |
Bacillus subtilis as a Model Organism | |
| |
| |
Regulation of Transcription in Bacteria | |
| |
| |
Technologies and Modelling | |
| |
| |
Systems Biology Approach to Transcriptional Modelling | |
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| |
RNA Metabolism | |
| |
| |
Applications of RNA Metabolic Analysis | |
| |
| |
Circadian Clock | |
| |
| |
Nature of the Circadian Clock | |
| |
| |
Entrainment | |
| |
| |
Multiple Pathway Integration | |
| |
| |
Resources for Systems Biology | |
| |
| |
Determining Protein Function from Sequence | |
| |
| |
Functional Sites via Structural Recognition | |
| |
| |
Exploitation of Features | |
| |
| |
Regulation, Transcription and Signalling | |
| |
| |
Use of Gene Expression Data | |
| |
| |
Systems Modelling | |
| |
| |
International Collaborations on Systems Biology Tool Development | |
| |
| |
Cellular Systems Biology | |
| |
| |
Intergovernmental Collaboration on Bacterial Systems Biology | |
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| |
National Programmes on Cellular Systems Biology | |
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| |
Local and Worldwide Scientific Collaboration | |
| |
| |
National Programmes | |
| |
| |
International Survey of Systems Biology | |
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| |
European Intergovernmental Programmes | |
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| |
USA Glue Grants | |
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| |
US Integrative Cancer Biology Programme | |
| |
| |
Informal but Structured International Collaboration | |
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| |
A Major FP7 Initiative in Systems Biology | |
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| |
Projects in Systems Biology Research | |
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| |
| |
Developmental Biology and Ageing | |
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| |
Introduction | |
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| |
The Importance of Developmental Biology and Ageing | |
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| |
Plant Development | |
| |
| |
Leaf Biology | |
| |
| |
Plant Research | |
| |
| |
Arabidopsis thaliana as a Model Organism | |
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| |
Growth Factors | |
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| |
Integrated Approach to Leaf Development | |
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| |
Developmental Biology Technologies | |
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| |
Results | |
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| |
Impact | |
| |
| |
Stem Cells and Development | |
| |
| |
Stem Cell Databases and Bioinformatics Tools | |
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| |
Stem Cell Genomic Data | |
| |
| |
Mitochondria and Ageing | |
| |
| |
Evolutionary Conserved Mechanisms | |
| |
| |
Databases for Model Organisms and Developmental Biology | |
| |
| |
Mitochondria Signalling | |
| |
| |
Metabolic Processes | |
| |
| |
Nuclear Receptors and Ageing | |
| |
| |
Nuclear Receptors | |
| |
| |
Nuclear Receptor Networks | |
| |
| |
Databases and Bioinformatics Tools | |
| |
| |
Implementation in the Seventh Framework Programme | |
| |
| |
Stem Cells | |
| |
| |
| |
Resources Supporting Bioinformatics and Systems Biology Research | |
| |
| |
| |
Databases, Computational Tools and Services | |
| |
| |
Introduction | |
| |
| |
Computational Resources | |
| |
| |
Major Gateway to Collaborative Research | |
| |
| |
A Central Resource Gateway | |
| |
| |
General Search Tool | |
| |
| |
Tools and Services | |
| |
| |
Interlinking of Tools and Databases | |
| |
| |
Distributed Development of Resources | |
| |
| |
Centres and Partners | |
| |
| |
Collaborative Bioinformatics Resource and Infrastructure Projects | |
| |
| |
Database Infrastructure | |
| |
| |
Fungal Database | |
| |
| |
Distributed Annotation System | |
| |
| |
Distributed Annotation | |
| |
| |
Annotation Server Information Service | |
| |
| |
Database Grid Integration | |
| |
| |
A Bioinformatics Grid for Europe | |
| |
| |
Grid Connectivity and Worldwide Access | |
| |
| |
Objectives of a Grid Infrastructure | |
| |
| |
Expected Grid Results | |
| |
| |
Linked Databases | |
| |
| |
Linked Tools | |
| |
| |
Open Software Linked Tools | |
| |
| |
Automated Gene Finding | |
| |
| |
Manual Versus Automated Gene Finding | |
| |
| |
Sequence Motif Analysis | |
| |
| |
Integrating Promoter Motif Analysis and Gene Expression | |
| |
| |
Protein Family Analyses | |
| |
| |
Ontologies | |
| |
| |
Gene Ontology | |
| |
| |
Gene Ontology Annotations | |
| |
| |
Open Biomedical Ontologies | |
| |
| |
Medical Ontologies | |
| |
| |
Text Mining | |
| |
| |
Reference Searching Plus Full Data Overview | |
| |
| |
Text Mining on Texts | |
| |
| |
Systems Biology Toolboxes | |
| |
| |
Systems Biology Toolboxes for Experimentalists | |
| |
| |
Systems Biology Toolbox Applications Procedures | |
| |
| |
Yeast Systems Biology | |
| |
| |
Expression Tools | |
| |
| |
Power-Law Analysis Tools | |
| |
| |
Multigenic Disease Modelling Platforms | |
| |
| |
Modelling Thousands of Reactions | |
| |
| |
Platform for Editing, Analysing and Varying Biochemical Models | |
| |
| |
Object Classes for Biological Entities from Gene to Cell | |
| |
| |
Stochastic Cell Simulation | |
| |
| |
| |
Supporting Infrastructures | |
| |
| |
Introduction | |
| |
| |
Wet-Laboratory Infrastructure and Data | |
| |
| |
Education, Human Resources and Publications | |
| |
| |
Wet-Laboratory Research Infrastructures | |
| |
| |
European Collaborative Projects | |
| |
| |
A European Systems Biology Institute | |
| |
| |
Workshop on Research Infrastructures | |
| |
| |
Model Organism Biobanks | |
| |
| |
Protein Structure Facilities | |
| |
| |
Genomics | |
| |
| |
Proteomics | |
| |
| |
Imaging Living Systems | |
| |
| |
Three-Dimensional Electron Microscopy | |
| |
| |
Research Infrastructures: Future Priorities | |
| |
| |
European Strategy Forum on Research Infrastructures | |
| |
| |
Future Infrastructures for Bioinformatics | |
| |
| |
Bioinformatics Infrastructures for Systems Biology | |
| |
| |
Medical Information Systems | |
| |
| |
Medical Informatics | |
| |
| |
Knowledge Management Systems | |
| |
| |
Choices of Systems Complexity | |
| |
| |
Education | |
| |
| |
School of Bioinformatics | |
| |
| |
Training Workshops and Courses | |
| |
| |
Outreach | |
| |
| |
| |
Disease-Related Collaborative Research and Computational Biology | |
| |
| |
| |
Infectious and Major Diseases | |
| |
| |
Introduction | |
| |
| |
Approach to Disease Research | |
| |
| |
Computational Biology and Disease | |
| |
| |
Viral and Bacterial Pathogens | |
| |
| |
Cardiovascular-Pulmonary Disease | |
| |
| |
Diabetes | |
| |
| |
Neurological Diseases | |
| |
| |
Immunology | |
| |
| |
Drug Development References | |
| |
| |
Viral Pathogens | |
| |
| |
HIV/AIDS and Hepatitis C Virus/Hepatitis C Coordinated Studies and Databases | |
| |
| |
Bioinformatics Prediction of HIV Antiretroviral Resistance Trajectory | |
| |
| |
HIV Genotypes | |
| |
| |
HCV Sequence Alignment | |
| |
| |
Herpes | |
| |
| |
Bacterial Pathogens | |
| |
| |
Pathogens Bacillus anthracis and Staphylococcus aureus, Using Bacillus subtilis | |
| |
| |
Bacillus Cell Factory | |
| |
| |
Streptomyces lividans | |
| |
| |
Protein Secretion in Streptomyces | |
| |
| |
Cardiovascular-Pulmonary Diseases and Diabetes | |
| |
| |
Congestive Heart Failure, Chronic Obstructive Pulmonary Disease and Type-2 Diabetes | |
| |
| |
Diabetes Screening | |
| |
| |
Proteomics and Modelling Approaches | |
| |
| |
Neurological Diseases | |
| |
| |
Systems Biology of the Neuron | |
| |
| |
Macular Degeneration | |
| |
| |
Modelling Molecular Interaction Networks | |
| |
| |
Proteomics Support | |
| |
| |
Immunology | |
| |
| |
Immunology Grid Models | |
| |
| |
Drug Development | |
| |
| |
Biosimulation in Drug Development | |
| |
| |
Mass-Spectrometric Resolution of Protein Phosphorylation in Hormonal Signalling | |
| |
| |
Metabolic Fates of Pharmaceuticals in Living Cells | |
| |
| |
Microcompartments Associated with Microtubular Networks | |
| |
| |
Regulation of Pancreatic �- and �-Cells | |
| |
| |
Neuronal and Systemic Models of Mental Diseases and Sleep Regulation | |
| |
| |
Synchronisation of Nephron Pressure and Flow Regulation | |
| |
| |
Models of Full-Scale Cardiac Arrhythmias | |
| |
| |
Spatio-temporal Organisation of Intracellular and Intercellular Ca<sup>2+</sup> Dynamics | |
| |
| |
Modelling of Molecular Regulatory Mechanisms of Circadian Rhythms | |
| |
| |
Deep Brain Stimulation and Medication | |
| |
| |
Biological Networks, Data Analysis and Pharmacokinetic Models | |
| |
| |
Modelling Human Metabolism, Body Weight Regulation and the Treatment of Diabetes | |
| |
| |
Live Cell Imaging by Use of Interference Microscopy | |
| |
| |
Application of Methods from Non-linear Dynamics to Describe Complex Cellular Phenomena | |
| |
| |
Implementation in the Seventh Framework Programme | |
| |
| |
Innovative Medicines Initiative | |
| |
| |
Seventh Framework Programme Research Projects in the Systems Biology of Disease | |
| |
| |
| |
Cancer | |
| |
| |
Introduction | |
| |
| |
Cancer Research Programmes | |
| |
| |
The Nature of Cancer | |
| |
| |
Challenges of Cancer Research | |
| |
| |
Relevance of Collaborative Research Projects | |
| |
| |
Nature of Cancer and Biology and Genetics of Cells and Organisms | |
| |
| |
Systems Biology of Cancer | |
| |
| |
Experimental and Clinical Data and Theoretical Models | |
| |
| |
Tumour Viruses | |
| |
| |
Role of Chronic Infections | |
| |
| |
Bioinformatics and Technology Platform | |
| |
| |
Cellular Oncogenes | |
| |
| |
Oncogenes Mutation Databases | |
| |
| |
Alternative Transcripts as Cancer Markers | |
| |
| |
Growth Factors and Their Receptors | |
| |
| |
Cell Growth Modelling | |
| |
| |
Cytoplasmic Signalling Circuitry | |
| |
| |
Ras/Raf/MEK/ERK and JAK/STAT Signalling | |
| |
| |
MAPK Signalling | |
| |
| |
Wnt and ERK Pathways | |
| |
| |
Regulatory Single-Nucleotide Polymorphisms | |
| |
| |
Cell Cycle | |
| |
| |
Cell Cycle Functional Modules | |
| |
| |
Tumour Suppressor Genes | |
| |
| |
pRb Tumour Suppressor | |
| |
| |
P53 and Apoptosis | |
| |
| |
Role of p53 | |
| |
| |
p53 and Mdm2 Feedback Loops | |
| |
| |
p53 Mutations | |
| |
| |
p53 Database | |
| |
| |
Apoptosis Modelling | |
| |
| |
p53, p63 and p73 Comparisons | |
| |
| |
Cell Immortalisation, Tumourigenesis and Senescence | |
| |
| |
Irreversible Growth, Apoptosis and Premature Senescence | |
| |
| |
Predictive Dynamic Model | |
| |
| |
Multistep Tumourigenesis | |
| |
| |
Virtual Tumour Progression Features | |
| |
| |
Succession of Genetic Mutations in Colon Cancer | |
| |
| |
Genomic Integrity and the Development of Cancer | |
| |
| |
DNA Repair | |
| |
| |
Angiogenesis and Lymphangiogenesis | |
| |
| |
Angiogenesis | |
| |
| |
Lymphangiogenisis | |
| |
| |
Tumour Microenvironment Interactions | |
| |
| |
Metastasis | |
| |
| |
Metastasis of Breast Cancer | |
| |
| |
Tumour Immunology and Immunotherapy | |
| |
| |
Cancer Immunotherapy | |
| |
| |
Implementation in the Seventh Framework Programme | |
| |
| |
Seventh Framework Programme Research Project in the Systems Biology of Cancer | |
| |
| |
Implications of the New Project | |
| |
| |
| |
Genetic Variation and Diseases | |
| |
| |
Introduction | |
| |
| |
Background | |
| |
| |
Call to Action | |
| |
| |
Genetic Variation Workshop | |
| |
| |
Genetic Variation Workshop Organisation and Goals | |
| |
| |
Editorial Encouragement | |
| |
| |
Status of Genetic Variation Research | |
| |
| |
Value of Cross-Linking Data | |
| |
| |
Linked Databases | |
| |
| |
Genetic Variation Data Sources | |
| |
| |
New Elements Facilitating Data Integration | |
| |
| |
Genotype to Phenotype | |
| |
| |
Biological and Medical Research: Genotype to Phenotype | |
| |
| |
Data and Analysis Challenges | |
| |
| |
Standards and Ontologies | |
| |
| |
Data Submission | |
| |
| |
Display and Analysis Tools | |
| |
| |
Analysis Challenges | |
| |
| |
Linking to Systems Biology Analysis | |
| |
| |
Databases | |
| |
| |
Databases to Be Linked | |
| |
| |
Approaches to Linking Databases in the Public Domain | |
| |
| |
Data Access | |
| |
| |
European-Level Support and International Collaboration | |
| |
| |
National-Level Programmes | |
| |
| |
Role of Model Organism Databases | |
| |
| |
Data Generation | |
| |
| |
Related Genetics Research and Infrastructures: | |
| |
| |
Biobanks and Testing | |
| |
| |
Control Populations | |
| |
| |
Copy Number Variation | |
| |
| |
Patient as Data Source | |
| |
| |
Data-Taking Procedures | |
| |
| |
Genetic Etiology | |
| |
| |
The Way Forward | |
| |
| |
Obstacles | |
| |
| |
Linking as a Solution | |
| |
| |
Hub Software | |
| |
| |
Customised Entry Points | |
| |
| |
Principal Conclusions on Linking Genetic Variation Databases | |
| |
| |
Research in the Fifth Framework Programme and the Sixth Framework Programme | |
| |
| |
Population Genetics | |
| |
| |
Down's Syndrome and Relevant Genetic Regions | |
| |
| |
Experimental Tools for Studying Genetic Variation | |
| |
| |
Genetic Variation Mapping Data | |
| |
| |
QTL Data | |
| |
| |
Software Tools | |
| |
| |
Next Steps | |
| |
| |
A Major Seventh Framework Programme Initiative in Genetic Variation | |
| |
| |
Projects in Genetic Variation Research | |
| |
| |
Implications of New Projects | |
| |
| |
| |
Science Management, Perspectives and Conclusions | |
| |
| |
| |
Science Management | |
| |
| |
Introduction | |
| |
| |
Motivation | |
| |
| |
Framework Programmes for Research | |
| |
| |
Bioinformatics and Systems Biology Research | |
| |
| |
Methods for Executing the Specific Programme | |
| |
| |
Funding Methods | |
| |
| |
Topics in Calls for Proposals | |
| |
| |
Proposal Evaluation | |
| |
| |
Nature of Contracts and Grant Agreements | |
| |
| |
Project Management | |
| |
| |
How To Participate and Develop Proposals | |
| |
| |
How To Participate in Research Projects | |
| |
| |
European and International Participation and Collaboration | |
| |
| |
Calls for Proposals | |
| |
| |
Mechanics of Proposal Preparation | |
| |
| |
Support Services for the Mechanics of Proposal Preparation | |
| |
| |
Finding Partners for Proposals | |
| |
| |
Documents Relevant to the Proposal Process | |
| |
| |
Characteristics of Proposals | |
| |
| |
Evaluation of Proposals | |
| |
| |
Evaluation Process | |
| |
| |
Evaluation Criteria | |
| |
| |
Announcement of Evaluation Results | |
| |
| |
Project Negotiation | |
| |
| |
FP7 Negotiating Guidelines | |
| |
| |
Financial and Legal Negotiations | |
| |
| |
Negotiation Relevant Documents | |
| |
| |
Negotiation Key Points | |
| |
| |
Operating Project Attributes and its Management | |
| |
| |
The Model Grant Agreement | |
| |
| |
Project Coordination and Management Structures | |
| |
| |
Role of the Commission Scientific Officer | |
| |
| |
Role of Commission Financial and Contract Officers | |
| |
| |
Contractual and Financial Obligations | |
| |
| |
Role of Contracts in Collaboration | |
| |
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Model Grant Agreements | |
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Project Reporting | |
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Information Dissemination | |
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Publications and Websites | |
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A Systems Biology Website | |
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A Bioinformatics Website | |
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IPR and Exploitation | |
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IPR Rules | |
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Approaches to IPR Policy | |
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Open Source | |
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IPR and Commercial Exploitation Support Services | |
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Perspectives | |
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Introduction | |
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Role of Perspectives | |
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Bioinformatics | |
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Bioinformatics Perspectives | |
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Model Systems and Biobank Resources | |
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Standards and Ontologies | |
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Obtaining Data Within and Beyond Present "Omics", Extending Databases | |
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Systems Biology | |
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Systems Biology Perspectives | |
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Developing Systems Biology: Cellular and Subcellular Systems | |
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Multiple Interacting SysSystemstems at the Cellular and Physiological Levels | |
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Physiologysiology | |
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Biotechnology | |
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Synthetic Biology | |
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Disease | |
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Applying Systems Biology to Disease, Medicines and Treatment | |
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Systems Biology of Targeted Diseases | |
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Therapeutic Applications of Computational Biology and Chemistry | |
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Seventh Framework Programme | |
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Health Research | |
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Physiological Integration | |
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Longer Term | |
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Systems Biology Forward Look | |
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Very Long Term | |
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Outstanding Results and Conclusions | |
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Introduction | |
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Tests of the Value of Collaborative Research | |
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The Impact of Collaborative Research | |
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Outstanding Resources Created | |
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Integrated Data Access Capabilities | |
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Establishment of Standards and Repository for Gene | |
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Expression Data | |
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A European Bioinformatics Grid and Linked Resources | |
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European Virtual Institute of Genome Annotation | |
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European School of Bioinformatics and Training and Outreach | |
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Outstanding Scientific Results | |
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The Majority of Human DNA Is Transcribed into RNA | |
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Understanding the Dynamic Behaviour of the p53-Mdm2 Network | |
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Understanding the Dynamics of Spindle Formation in Cells | |
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Establishment of the Role of Alternative Transcription and Splicing in Cancer | |
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Small-Ligand Binding | |
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Multiple Drug Treatment for HIV/AIDS Drug-Resistant Mutation Pathways | |
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Cancer as A Signalling Disease, Applied to Protein Kinase Pathways | |
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Future Project Outcomes | |
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Overall Conclusions | |
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The Challenge | |
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Successes of Collaborative Research in Bioinformatics and Systems Biology | |
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References | |
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Index | |