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I WHY METAGENOMICS? 12 What Is Metagenomics?, 13 "What Microbes Can Do: Four Examples, 15 Microbes Modulate and Maintain the Atmosphere, 15 Microbes Keep Us Healthy, 17 Microbes SIpport Plant Growth and Suppress Plant Disease, 18 Microbes Clean Up Fuel Leaks, 19 Invisible Communities: Global Impact, 19 Understanding Microbial Communities, 21 The Limits of Pure Culture, 21 The Genomics Promise, 23 Why Genomics i Not Enough, 25 Most Microbes Cannot Be Cultured, 25 Microbial Diversity and Variation Have No Limits, 27 Metagenomics Offers a Way Forward, 29 Metagenomics Can Contribute to Advances in Many Fields, 31 2 A NEW LIGHT ON BIOLOGY 33 What Is a Genome?, 33 What Is a Species?, 35 What Is the Role of Microbes in Maintaining the Health of Their Hosts?, 37 How Diverse is Life?, 38 How Do Microbial Communities Work?, 40 How Do Microbial Communities React to Change?, 43 Flow Do Microbes Evolve?, 44 What Ecological and Evolutionary Roles Do Viruses Play?, 46 3 FROM GENOMICS TO METAGENOMICS: FIRST STEPS 47 Sequencing Is Just One Kind of Metagenomics, 48 Pioneering Projects in Metagenomics, 50 The Acid Mine Drainage Project, 50 The Sargasso Sea Metagenomic Survey and Community Profiling, 53 The Soil-Resistome Project, 55 T he Hiuman-Microbiorne Project, 57 Viral Metagenomics, 58 4 DESIGNING A SUCCESSFUL METAGENOMICS PROJECT: BEST PRACTICES AND FUTURE NEEDS 60 Paralle!s with Traditional Microbial Genome Sequencing, 60 Metagenomics Step by Step, 63 Flabitat Selection, 63 Samp ing Strategy, 64 Macromolecule Recovery, 65 Getting the Most Out of Metagenomics Studies, 67 [,OS rRNA-Based Surveys, 67 16S rRNA Phylogenetic and Functional Anchors: A Hybrid Approach, 70 Generation of Large-Scale DNA Sequence, 70 Assembling Whole Genomes, 71 Gene-Centric Analyses, 73 Hybridization- and Array-Based Analyses, 74 Flnction Based Analyses of Microbial Communities, 76 Advancing the Field, 77 Sequencing Technology, 77 Gene-Expression Systems, 79 Single-Ceii Analyses, 80 Methods for Culturing Uncultured Species, 82 Basic Microbiology, 83 Understanding Microbial Habitats and Collecting Metadata, 83 Dowrstream Development of Metagenomics, 84 5 DATA MANAGEMENT AND BIOINFORMATICS CHALLENGES OF METAGENOMICS 85 Genomic Data, 85 Metagenomic Data, 88 The Importance of Metadata, 90 Databases for Metagenomic Data, 92 Software, 94 Analysis of Metagenomic Sequence Data, 95 6 THE INSTITUTIONAL LANDSCAPE FOR METAGENOMICS: NEW SCIENCE, NEW CHALLENGES 98 Major Stakeholders in Metagenomics, 98 The Scientific Community, 98 Funding Agencies, 98 international Coordination, 99 Education and Training, 100 Other Institutional Issues, 102 Data Release, 102 Intellectua Property, 103 Metagenomics and the Convention on Biological Diversity, 104 Biosafety, 105 Outreach, 106 A BALANCED PORTFOLIO: MULTI-SCALE PROJECTS IN THE "'GLOBAL METAGENOMICS INITIATIVE" 1 07 The Vision, 107 Characteristics of Successful Large-Scale Projects, 108 Why Metagenomics Needs a "Big Science" Component, 109 What Kind of Large-Scale Projects in the Global Metagenomics Initiative and How Many?, 112 Expected Benefits of Large-Scale Metagenomics Projects, 113 Theory and Principles, 113 Understanding Specific Habitats, 114 Technical Advancement of the Field, 114 International Collaboration and Training, 115 Learning from Previous Large-Scale Genomics Projects, 115 The Human Genome Project, 116 The Arabidopsis Genomne Project, 117 Lessons for Metagenomics, 118 A Preliminary Road Map, 118 Phase 1: Choosing Model Communities, 118 Phase II: Planning and Initial Data-Gathering, 120 Phase II: Implementation, 122 Conclusion, 122