Contents:

Executive Summary Introduction to systems biology Key aspects and components of systems biology Applications of systems biology Emerging technologies and developments Case studies and success stories Interviews with thought leaders in systems biology Chapter 1 Introduction to systems biology Summary Introduction Introduction to systems biology Research applications of systems biology The evolution of systems biology Mathematical modeling Physiology and cell biology And now… Change from reductionist biology New technologies Chapter 2 Key aspects and components of systems biology Summary Introduction Approaches to systems biology Bottom-up approach Top-down approach The reality in systems biology: a combination of bottom-up and top-down Key aspects of systems biology System structures System dynamics The control method The design method Four basic steps in systems biology Key technology components of systems biology The "omics" Genomics Transcriptomics Proteomics The emerging "omic" – metabolomics Data storage and mining Bioinformatics Network biology Pathway analysis Modeling and biosimulations Chapter 3 Applications of systems biology Summary Introduction Drivers of systems biology Increase in R&D costs Examples of how systems biology can lower costs: Fall in R&D productivity Drug failures in clinical trials Systems biology in pharmaceutical discovery and development Identification of drug targets Examples of success: Improving the quality of lead compounds Improved ADMET prediction Fewer costly failures due to toxicity Examples of success: Optimization of clinical trials Example of success: Identification of biomarkers Biomarkers for drug discovery and validation Examples of success: Biomarkers for toxicity Biomarkers and segmentation of patient populations Examples of success: Biomarkers and the FDA's Critical Path Initiative Development of combination drug therapies Additional indications for pharmaceuticals already on the market Improved lead prioritization and optimization Better clinical trials strategies Regulatory/industry initiatives The FDA's Critical Path Initiative Examples of success: National Institutes of Health (NIH) roadmap Diagnostic applications for systems biology Cancer Diagnosis of cancer Delineation of cancer by sub-groups for therapeutic decisions Monitoring of efficacy of treatment Examples of success: Diabetes Example of success: Systems biology in bioprocess engineering Examples of success: Additional applications for systems biology Agricultural improvement Examples of success: Cosmetics Example of success: Biodefense Example of success: Bioremediation Examples of success: Conclusions Chapter 4 Emerging technologies and developments Summary Introduction RNAi siRNA – small interfering RNAs miRNA – microRNAs New proteomic technologies Antibody arrays Morphoproteomics Time-of-flight Mass Spectrometry (MS) Ion Trap MS Maldi-TOF Q-TOF MS Liquid Chromatography (LC) Q-TOF MS-MS spectrometer Emerging software developments Systems Biology Markup Language (SBML) Systems Biology Workbench (SBW) CellDesigner Cytoscape Pathway Tools Software from SRI PathwayStudio Central SRS Pathway Editor from Lion Bioscience AG Databases of interest PANTHER database of proteins KEGG: Kyoto Encyclopedia of Genes and Genomes SPAD: Signaling Pathway Database BIND: Biomolecular Interaction Network Database HPRD: Human Protein Reference Database GO: Gene Ontology DIP: Database of Interacting Proteins BioBase: Biological Databases / Biologische Datenbanken GmbH PDB: Protein Data Bank AfCS: Alliance for Cellular Signaling BioModels Database Initiatives in systems biology International initiatives E-Cell Project, Keio University, Japan Kitano Symbiotic Systems Project International Physiome Project Standard Metabolic Reporting Structures (SMRS) Virtual Cell Project – National Resource for Cell Analysis and Modeling BioSPICE Microbes Online European initiatives SystemsX European Interaction Proteome US initiatives Biocomputation Program, DARPA Genomes to Life Initiative, DOE Metabolic Engineering Working Group, Multiple Agencies National Centers for Systems Biology (NCSB), National Institute for General Medical Sciences (NIGMS), NIH Key academic centers MIT's Computational and Systems Biology Institute Harvard University's Department of Systems Biology The Center for Quantitative Biology, Princeton Systems Biology Group at the University of Stuttgart, Germany Intelligent Bioinformatics Systems Division (IBSD), German Cancer Research Center, Heidelberg, Germany What is holding system biology back? Lack of knowledge Genomic Proteomic Biomolecular Networks Need for better analytical tools Lack of computing power The conservative culture in Big Pharma Failed promises in the past Chapter 5 Case studies and success stories Summary Case studies Johnson & Johnson Pharmaceutical Research and Development, (J&JPRD) Integrative drug discovery using systems biology Examples of success: F. Hoffman-La Roche Some software tools Roche uses Examples of success: Pfizer Examples of success: Lilly Systems Biology (Singapore) GlaxoSmithKline's Scientific Computing and Mathematical Modeling (SCMM) group Additional success stories In silico target screen for ALS treatment (Harvard University) Creation of virtual asthma patients (Entelos/Aventis) Diabetes biomarkers Chapter 6 Interviews with thought leaders in systems biology Summary Introduction 1. What do you feel are systems biology greatest strengths? Adriano Henney Iya Khalil Karin Jorga 2. What do you feel is holding back systems biology from being used more widely? (other than a lack of trained personnel) AH IK KJ 3. Where do you feel systems biology has, and will have, the greatest impact in drug discovery and development – now, and in ten years? AH IK KJ Dr. Iya Khalil and Dr. Karin Jorga on success stories Q. Are there any success stories, or examples of successful use of systems biology that you can share? IK KJ Dr. Adriano Henney discusses how AstraZeneca moved into the field of systems biology Q. How did AstraZeneca become involved in systems biology? AH Chapter 7 Key companies in systems biology Introduction Non-profit organizations Institute for Systems Biology Overview Systems biology sector Main therapeutic focus Technology Collaborations Patents Pathway analysis Cellzome AG Overview Systems biology sector Main therapeutic focus Technology Collaborations Patents GeneGo Overview Systems biology sector Main therapeutic focus Technology Products Collaborations Licensing agreements Patents Hybrigenics SA Hybrigenics USA Overview Systems biology sector Main therapeutic focus Technology Products / Services Collaborations Patents Ingenuity Overview Systems biology sector Technology Products Services Licensing agreements Collaborations Patents Biosimulation and in silico modeling Gene Network Sciences Overview Systems biology sector Main therapeutic focus Technology Products Collaborations Licensing agreements Patents Genomatica Overview Systems biology sector Main therapeutic focus Technology Products Collaborations Licensing agreements Patents Kenna Technologies Overview Systems biology sector Primary therapeutic focus Technology Products Collaborations Patents Physiomics Plc Overview Systems biology sector Main therapeutic focus Technology Products Collaborations Patents Data management companies Genedata Overview Systems biology sector Main therapeutic focus Technology Products Collaborations Licensing agreements Patents Genstruct Overview Systems biology sector Main therapeutic focus Technology Collaborations Licensing agreements Patents BG Medicine Overview Systems biology sector Primary therapeutic focus Technology Collaborations Patents Chapter 8 Appendix References Journals General References Overviews Pharmaceutical Discovery Target Validation Lead Optimization In Silico Modeling Bioinformatics Systems biology for bioprocess engineering Biomarkers Pathways Some Websites of Interest: Overviews: U.S. Government Index List of Figures Figure 2.1: Basic steps in systems biology Figure 3.2: Applications of systems biology Figure 3.3: New chemical entities (NCEs) approved by year, 1999-2004 Figure 3.4: Drug discovery costs, 2003 Figure 3.5: Causes of drug failures, 2001 List of Tables Table 3.1: Time and cost for compound discovery and development Table 3.2: Time and cost for preclinical and clinical testing of lead compounds Table 7.3: Key ISB patents and patent applications Table 7.4: Key Cellzome AG patents Table 7.5: Key GeneGo patent applications Table 7.6: Key Hybrigenics patents and patent applications Table 7.7: Key Ingenuity Medicine patents and patent applications Table 7.8: Key GNS patent applications Table 7.9: Key Genomatica patents Table 7.10: Key Kenna Technologies patent Table 7.11: Key Physiomics patent Table 7.12: Key Genstruct patent applications Table 7.13: Key BG Medicine patents and applications

Companies Mentioned

- Johnson & Johnson Pharmaceutical Research and Development - F. Hoffman-La Roche - Pfizer - Lilly Systems Biology - GlaxoSmithKline - Cellzome AG - GeneGo - Hybrigenics SA - Ingenuity - Gene Network Sciences - Genomatica - Kenna Technologies - Physiomics Plc - Genedata - Genstruct - BG Medicine