Epigenomics in health and disease / edited by Mario F. Fraga and Agustin F. Fernandez.

Format:

Book

Contributor:

Fraga, Mario.

Fernández, Agustín F.

Series:

Translational epigenetics series

Language:

English

Subjects (All):

Epigenetics.

Medical genetics.

Genre:

Electronic books.

Physical Description:

1 online resource.

Place of Publication:

London : Academic Press, 2015.

System Details:

text file

Summary:

Reviews the technologically-driven study of the oganismal epigenome and associated translational impacts on future prognosis, diagnosis and therapies of disease. With next-generation sequencing technologies shaping our current knowledge of the role of epigenetics in normal development, aging, and disease, Epigenomics in Health and Disease discusses the consequences for diagnostics, prognostics, and disease-based therapies made possible by the study of the complete set of epigenetic modifications to the genetic material of human cells. Chapters also explore the latest findings of epigenome-wade research in disease-based profiling, epidemiological implications, epigenome-wide epigenetic studies, the cancer epigenome, and other pervasive disease categories. With coverage pertinent both to basic biology and translational research, Epigenomics in Health and Disease will be of particular interest for medical and bioscience researches and students seeking current translational knowledge in epigenesis and epigenomics. Key Features Critical reviews provide the means for reviewing and analyzing the epigenome as a whole as well as its translational potential Combines basic epigenomic knowledge with methodological and biostatistical topics related to technology and date analysis Includes coverage of relatively new topics including DNA methylation dynamics during development and differentiation, genome-wide histone post-translational modifications during development and differentiation, and genome-wide DNA methylation changes during aging Book jacket.

Contents:

1 The Role of the Genetic Code in the DNA Methylation Landscape Formation / Holger Heyn Heyn, Holger

1.1 Bringing the Genetic Code to Life 1

1.2 Intrinsic Properties of DNA 3

1.3 Sequence-Pattern-Dependent DNA Methylation Profiles 5

1.4 DNA-Binding Factors Shaping the Epigenetic Landscape 6

1.5 The Dynamics of Transcription-Factor-Mediated DNA hypomethylation 8

1.6 Translational Potential of Demethylation Dynamics 9

1.7 DNA Methylation Quantitative Trait Loci 9

1.8 Genotype-Driven Variance in Human DNA Methylation Profiles 10

1.9 Epigenetic Mediator Function for Human Risk Phenotype Formation 11

1.10 Epitype Association Guiding the interpretation of Cancer Risk Polymorphisms 12

1.11 Closing Remarks 13

References 14

2 DNA Methylation Microarrays / Marina Bibikova Bibikova, Marina

2.1 Introduction 19

2.2 Infinium DNA Methylation Technology 21

2.2.1 BeadArray Platform 21

2.2.2 Infinium Assay 22

2.3 HumanMethylation450 Array Design and Performance 24

2.3.1 Design Challenges 24

2.3.2 Content Selection 25

2.3.3 Gene Coverage 27

2.3.4 CGI Coverage 27

2.3.5 Correlation with WGBS Data 29

2.4 HumanMethylation450 Array Advantages and Limitations 30

2.5 DNA Methylation Data Analysis 30

2.6 Use of Methylation Arrays in Epigenetic Studies 35

2.6.1 DNA Methylation and Cancer 35

2.6.2 DNA Methylation and Aging 35

2.6.3 Epigenome-Wide Association Studies 36

2.7 Conclusion 37

References 39

3 Ultra-Deep Sequencing of Bisulfite-Modified DNA / Tingting Qin Qin, Tingting, Yongseok Park Park, Yongseok, Maria E. Figueroa Figueroa, Maria E., Maureen A. Sartor Sartor, Maureen A.

3.1 Introduction 47

3.2 Sample Preparation and Study Design Considerations for Ultra-Deep Bisulfite Sequencing 49

3.3 Technical Considerations for Ultra-Deep Bisulfite Sequencing Approaches 52

3.3.1 Sequencing Depth 52

3.3.2 Read Length 53

3.3.3 Quality Controls 54

3.3.4 Approaches to Mapping to a Reference Genome 55

3.4 Testing for Differential Methylation 58

3.5 Identifying Enriched or Differentially Methylated Transcription Factor-Binding Sites 62

3.6 Data Visualization and Annotation 62

3.7 Gene Set Enrichment Strategies 64

3.8 Published Applications 65

3.8.1 Using ERRBS to Study Leukemia 65

3.8.2 WGBS in Cancers 66

3.9 Conclusions and Future Directions 67

References 68

4 Bioinformatics Tools in Epigenomics Studies / Gustavo F. Bayón Bayón, Gustavo F., Agustín F. Fernández Fernández, Agustín F., Mario F. Fraga Fraga, Mario F.

4.1 Introduction 74

4.2 Types of Experiments and Data Characteristics 74

4.2.1 DNA Methylation 75

4.2.2 Histone Modifications 77

4.3 Bioinformatics Tools 78

4.3.1 R/Bioconductor 78

4.3.2 Open Bioinformatics Foundation 88

4.3.3 Online Tools 90

4.3.4 Software Tools 93

4.4 Reproducible Research 98

4.4.1 Literate Programming 98

4.4.2 Orthogonal Validation 99

4.4.3 Provenance 100

4.4.4 Open Source 100

4.5 Conclusion 101

References 101

5 Noncoding RNA Regulation of Health and Disease / Nicolas Léveillé Léveillé, Nicolas, Carlos A. Melo Melo, Carlos A., Sonia A. Melo Melo, Sonia A.

5.1 Introduction 109

5.2 Noncoding RNAs 110

5.2.1 Long Noncoding RNAs 111

5.2.2 Mechanisms of Action 112

5.2.3 Enhancer RNAs 116

5.3 Circulating Noncoding RNAs 118

5.4 Exosomes: Biogenesis and Cancer Biomarkers 119

5.5 Conclusion 121

References 121

6 Genome-Wide DNA Methylation Changes During Aging / Kevin C. Johnson Johnson, Kevin C., Brock C. Christensen Christensen, Brock C.

6.1 Introduction 127

6.2 Observed Differences in DNA Methylation Patterns with Aging 128

6.3 Causes of Age-Related DNA Methylation Changes 132

6.4 Tissue-Specific and Tissue-Independent Age-Associated DNA Methylation 133

6.5 Implications: Age-Associated DNA Methylation and Disease Risk 135

6.6 Environmental Factors that Influence DNA Methylation Patterns Over Time 137

6.7 DNA Methylation as an Epigenetic/Biologic Clock 138

6.8 Summary and Future Studies 139

References 140

7 The Dynamics of Histone Modifications During Aging / Anthony J Bainor Bainor, Anthony J, Gregory David David, Gregory

7.1 Introduction 145

7.2 Part 1: Nucleosome Density and Aging 146

7.3 Part 2: Histone Variants 148

7.3.1 Histone H3 148

7.3.2 Histone H2A 149

7.3.3 Senescence and Histone Variants 149

7.4 Part 3: Histone Modifications 150

7.4.1 Activating Histone Marks 151

7.4.2 Repressive Histone Marks 153

7.4.3 Senescence, DNA Damage, and Histone Modifications 154

7.5 Progeria: Accelerated Aging Due to Nuclear Architecture Dysfunction 156

7.6 Conclusion 157

References 157

8 Epigenomic Studies in Epidemiology / Valentina Bollati Bollati, Valentina, Valeria Motta Motta, Valeria, Simona lodice lodice, Simona, Michele Carugno Carugno, Michele

8.1 Introduction: From Classical Epidemiology to Epigenomic Epidemiology 163

8.2 The Choice of an Appropriate Study Design 164

8.2.1 Cohort Studies 164

8.2.2 Birth Cohort Studies 165

8.2.3 Cross-Sectional Studies 166

8.2.4 Case-Control Studies 166

8.2.5 Nested Case-Control Studies 167

8.2.6 Twin Studies 168

8.3 Environmental Epigenetics 169

8.4 Validation of Results 169

8.5 Biologic Sample Selection 170

8.6 Methods Selection 174

8.6.1 DNA Methylation 174

8.6.2 Histone Modifications 176

8.6.3 miRNAs 176

8.7 Extracellular Nucleic Acid Markers 177

8.8 Sample Size Selection and Statistics 178

8.9 Confounding Factors and Effect Modifiers: Dealing with Complex Systems 179

8.10 Conclusions and Perspectives 180

References 180

9 The DNA Methylomes of Cancer / Renée Beekman Beekman, Renée, Marta Kulis Kulis, Marta, José Ignacio Martín-Subero Martín-Subero, José Ignacio

9.1 Introduction to the Epigenetic Language 183

9.2 Definition and Classical Roles of DNA Methylation 184

9.3 DNA Methylation in Cancer: A Historical Perspective 185

9.4 High-Throughput Approaches to Detect DNA Methylation Changes 186

9.5 The Genome-Wide DNA Methylome of Cancer Cells: Overview and General Insights 189

9.6 DNA Methylation Changes Outside Promoters Is a Major Finding in Cancer 191

9.7 Altered DNA Methylation in Cancer Is Biased Toward Particular Chromatin States 193

9.8 Normal Reference Samples of the Cancer Epigenome 195

9.9 DNA Methylation Changes: Cause or Consequence of Cancers 196

9.10 Clinical Use of DNA Methylation in Cancer 198

9.11 Conclusions and Future Directions 200

Acknowledgments 202

References 202

10 Genome-Wide Epigenetic Studies in Neurologic Diseases / Ashwin Woodhoo Woodhoo, Ashwin

10.1 Introduction 209

10.2 Neuroepigenetics in the "OMICS" Era 210

10.2.1 Alzheimer Disease 210

10.2.2 Parkinson Disease 214

10.2.3 Huntington Disease 216

10.2.4 Multiple Sclerosis 219

10.2.5 Major Psychosis 220

10.2.6 Epilepsy 222

10.2.7 Diabetic Neuropathy 223

10.3 Conclusion 223

References 229

11 Epigenetic Deregulation in Autoimmune Disease / Damiana Álvarez-Erríco Álvarez-Erríco, Damiana, Esteban Ballestar Ballestar, Esteban

11.1 The Loss of Immune Tolerance: Breaking Bad 235

11.2 Epigenetic Regulation 237

11.2.1 DNA Methylation 237

11.2.2 Histone Modifications 238

11.3 Local and Systemic Autoimmune Disorders: importance of the Environment 238

11.4 Epigenetic Regulation in Autoimmune Disorders 239

11.4.1 Systemic or Rheumatoid Autoimmune Disorders 239

11.4.2 Tissue-Specific AIDs 246

11.5 Molecular Characterization of Common Pathogenic Routes: Autoimmunity in the Twenty-First Century 248

11.5.1 Toward Accurate Diagnosis 249

11.5.2 Toward Individual-Based Treatment 249

11.6 Conclusions and Perspectives 250

References 250

12 Genome-Wide DNA and Histone Modification Studies in Metabolic Disease / Charlotte Ling Ling, Charlotte, Tina Rönn Rönn, Tina

12.1 Introduction 255

12.2 Type 2 Diabetes and Epigenetic Modifications 257

12.3 Obesity and Epigenetic Modifications 262

12.4 Do Diet and Exercise Interventions Alter the Epigenetic Pattern and Potentially Risk for Metabolic Diseases 263

12.5 Does the Intrauterine Environment Alter the Epigenetic Pattern and Potentially Risk for Metabolic Diseases 265

12.6 Conclusions 265

References 266

13 Clinical Applications of Epigenomics / Michael A. McDevitt McDevitt, Michael A.

13.1 Introduction 272

13.2 Cancer Is an Epigenetic Disease 272

13.2.1 Methylation as Qualitative Disease Markers: Illuminating Disease Biology and Facilitating Accurate Diagnosis 273

13.3 Epigenomics as a Tool to Unravel Cancer Mechanisms 275

13.4 Methylation Profiling in Other Cancers 276

13.5 Methylation Markers as Clinical Predictors of Disease Progression and the Potential Power of Quantitative Biomarkers 277

13.6 Genetic Mutation in Epigenetic Regulators 278

13.7 Other Epigenetic Methylation Patterns in Cancer 279

13.7.1 Gene Body 279

13.7.2 Hypomethylation Regions, LOCKs. and LADs 280

13.7.3 Shores 281

13.8 Other Recurrent Epigenomic Patterns in Cancer (Nonmethylation) 281

13.8.1 Genome-Scale Epigenetic Reprogramming During Epithelial-to-Mesenchymal Transition 281

13.8.2 Polycomb Complexes and Bivalent Chromatin 282

13.8.3 Post-Translaiional Histone Modifications and Nucleosomes 282

13.8.4 RNA-Mediated Epigenetic Regulation 283

13.8.5 miRNA 284

13.8.6 LncRNA 284

13.9 Epigenomics and Epigenetic Therapy 285

13.10 Potential Applications of Epigenetic and Genetic Biomarkers with Epigenetic Therapies 285

13.10.1 TET2 Mutations and AZA Responses 286

13.10.2 MTls and Solid Tumors 286

13.11 Epigenome-Wide Association Studies for Common Human Diseases 287

13.12 Summary and Future Directions Related to Clinical Applications of Epigenomics 288

References 289.

Notes:

Includes index.

Description based on print version record.

Other Format:

Print version: Fraga, Mario. Epigenomics in Health and Disease.

ISBN:

0128004967

9780128004968

OCLC:

925286798

Access Restriction:

Restricted for use by site license.