Principles of Genetics and Molecular Epidemiology

Foreword
References
Preface
Acknowledgements
Contents
Contributors
1: Principles of Modern Epidemiology and Public Health
Introduction
Life-Course Epidemiology
Principles of Life-Course Research
Development over Time
Time and Place
Timing
Linked Lives
Free Will or Agency
Challenges for Life-Course Epidemiology
Translational Epidemiology
Postmodern Epidemiology
Need for a Refocus on Postmodern Epidemiology
Analysis Levels to be Considered in Postmodern Epidemiology
Postmodern Epidemiology Perspective
Final Considerations
References
2: Molecular Tools for Modern Epidemiology: From the Concepts to Clinical Applications
Introduction
PCR
Types of PCR
Multiplex PCR
Real-Time PCR
Reverse Transcription PCR
Digital PCR
Lamp
Principles of Karyotyping
FISH
Microarray
Immunoassays
Enzyme-Linked Immunosorbent Assay (ELISA)
Direct ELISA (Antigen-Coated Plate, Screening Antibody)
Indirect ELISA (Antigen-Coated Plate; Screening Antigen/Antibody)
Sandwich ELISA (Antibody-Coated Plate; Screening Antigen)
Competitive ELISA (Screening Antibody)
New Methods
Clinical Significance
Western Blot
Multiplex Western Blot (MWB)
Capillary Electrophoresis (CE) and Capillary Western Blotting (CWB)
Microfluidic Western Blotting
Single-Cell Western Blotting
Dot Blot
Far-Western Blotting
Clinical Significance
Flow Cytometry
Clinical Applications
Phenotypic Characterization of Blood Cells
Intracellular Antigen Expression
Characterization of Antigen-Specific Responses
Cell Cycle Analysis
Apoptosis
Proteomics
Studying the Proteome
Concluding Remarks
References
3: Genomic Tools in Clinical Epidemiology
Introduction
NGS in the Study of Relevant SNVs and SNPs for Epidemiological Surveillance
Implication of NGS Technologies on the Control of SARS-CoV-2 Pandemic
The Influence of Genomic Tools on the Management of Helicobacter pylori Infection
General Applications of NGS Technologies in Oncology Practices
Advances on the Pathogenesis and Treatment Knowledge of Rheumatoid Arthritis by Using NGS
Concluding Remarks
References
4: Epigenetics in Epidemiology
Introduction
Epigenetic Process
Epigenetic Technology Analysis
Overview of Bioinformatic Analysis of Epigenome
Epigenetic Biomarkers
Epigenetics in Pharmacology
Conclusions
References
5: Principles of Clinical Transcriptomics and Splicing
Introduction
The Leap From Classic Gene Expression Studies to Transcriptomics
General Overview of Transcriptomic Technologies
SAGE-Derived Sequencing Technologies
Microarrays
RNA-seq
Bulk Transcriptomics Profiling and Single-Cell Transcriptomics
Splicing and Alternative Splicing
Implications of Alternative Splicing in Clinics
Applications of Transcriptomics in Clinical Disease
Concluding Remarks
References
6: Proteomics Principles and Clinical Applications
Introduction
Proteome
Proteomics
Proteomics Databases and Tools
Proteomics Technologies
Proteomics in Health and Disease
Proteomics for the Diagnosis of Neurodegenerative Diseases
Alzheimer’s Disease (AD) and Related Dementias Diagnosis
Proteomic Studies in Parkinson’s Disease
Huntington’s Disease
Cancer
Mitochondria and Proteomics
Proteomics of Infectious Diseases
Viral Infections
Bacterial Infections
Parasitic Infections
Aging, Frailty, and Skeletal Muscle Wasting
Conclusions
References
7: Metabolomics: From Scientific Research to the Clinical Diagnosis
Introduction
The “Omics Science” in Human Health
Toward Personalized Medicine
Predictive Technologies in Human Diseases
How to Implement Clinical Analysis Through Metabolomics
Instrumentation in the Metabolomic Clinic
Mass Spectral Library and Bioinformatics
Conclusions
References
8: Microscopy Principles in the Diagnosis of Epidemic Diseases
Introduction
Brief History of the Development of the Microscope
Photonic Microscope
The Use of Microscopy in the Life Sciences
Generalities
Components of the Photon Microscope
Types of Photon Microscopes
Bright-Field Microscope
Dark-Field Microscope
Phase Contrast Microscope
Staining of Biological Samples, for Use in Different Types of Photon Microscopy
The Use of the Photon Microscope in Clinical Diagnosis
Microscopy as a Diagnostic Method
The Use of the Photon Microscope in Histopathology for the Diagnosis of Diseases
Diagnosis of Viral Infections
Diagnosis of Bacterial Infections
Diagnosis of Parasitic Infections
Use of the Microscope in Examination of Urine Sediment
Fluorescence Microscopy
Fluorophores
Excitation Spectrum
The Fluorescence Microscope
Confocal Microscopy
Architecture of the Confocal Microscope
Confocal Microscopy in Molecular Epidemiology: Clinical Applications and Further Directions
Confocal Microscopy in Ophthalmology
Confocal Microscopy in Dermatology
Rare Diseases and Confocal Microscopy
Electron Microscopy
Wave Particle Duality
Components of the TEM
Sample Preparation
The Role of the Electron Microscopy in Virus Diagnostic
The Role of the TEM in Viral Gastrointestinal Diseases
The Norovovirus
The Rotavirus
The Role of TEM in Viral Respiratory Diseases
The Influenza Virus
The Role of Electron Microscopy and the Last Pandemic
Concluding Remarks
References
9: Physiomics and Phenomics
Physiomics
Practical Applications of Physiomics
Drug Research
Organ Models
“The Human Physiome Project”
Phenomics
Practical Applications of Phenomics
Closing Remarks
References
10: Digital Health and Physiomics
Introduction
Digital Health
Wearables and Biosensors
Social Media and Health
Social Media in Healthcare
Monitoring and Retrieval of Official Information
Disease Detection
Timely Estimates and Forecasts of Disease Incidence
Situational Awareness During Emergency Response
Communication Surveillance
Global Awareness
Reaction to Public Health Campaigns and Messages
Applications
Digital Health and Physiome
Conclusion
References
11: Principles of Imaging for Epidemiologists
Introduction to Imaging Methods in Epidemiology
Imaging Applications in Neurological and Psychiatric Research
Illustrative Example: Population Imaging in Alzheimer’s Disease
Imaging Applications in Cardiovascular Research
Imaging Applications in Cardio-Metabolic Research
Imaging Applications in Cancer Research
Use of Imaging in Population-Based Epidemiological Studies
Study of Health in Pomerania (SHIP)
Cooperative Health Research in the Region Augsburg (KORA)
Generation R
Imaging Biobanks for Epidemiological Research
Analysis of Imaging Data from Population-Based Studies
Big Data Challenges
Multivariate Analysis in Imaging
Artificial Intelligence: Machine Learning and Deep Learning
Bayesian Statistics in Imaging
Limitations and Biases in Imaging Studies
Anatomical and Incidental Findings
Nonrepresentative Samples
Establishing Causal Relationships
Costs in Population Imaging
Concluding Remarks
References
12: Bioinformatics and Genomics for Epidemiologists
Introduction: Bioinformatics Applied to Modern Epidemiology
Applications of Bioinformatics in Modern Epidemiology
The Need for Clinical Bioinformaticians in the Era of Big Data in Epidemiology
Technical and Conceptual Limitations in Bioinformatics
Genome-Wide Association Studies
A Primer on GWAS and its Applications to Epidemiology
How Is the GWAS Approach Applied to Epidemiology?
Incorporating GWAS Findings into Epidemiology
Analyzing GWAS Data
Epigenome-Wide Association Studies
Methods for Conducting EWAS
Application of EWAS in Epidemiological Studies
Polygenic Risk Scores
Polygenic Risk Scores in Personalized Medicine
First Approaches within the Estimation of GRS
Determination of Genetic Risk Scores
Limitations of Polygenic Risk Scores when Applied to a Real-World Scenario
Perspectives for Bioinformatics and Genomics Using Systems Biology
Conclusions
References
13: Spatial Statistics and Health Sciences: Methods and Applications
Introduction
Descriptive Statistics
Global and Local Spatial Autocorrelation
Neighbours
Spatial Weights
Interpolation and Geostatistics
Variogram
Spatial Interpolation
Inverse Distance Weight
Kriging
Linear Models for Spatial Data
Spatial Lag Model
Spatial Autoregressive and Spatial Error Models
Inference with the Models
Other Spatial Models
Simultaneous Moving Average
Geographically Weighted Regression
Conclusion
References
14: Principles of Network Models and Systems Epidemiology
Introduction
Systems Epidemiology
Network Models
Probabilistic Graphical Models (PGM)
Neural Networks
Social Network Analysis (SNA)
Perspectives
Conclusions
References
15: Molecular Pharmacological Tools Applied to Epidemiology
Introduction
Drug Discovery
Target Identification
Validation of the Target
Lead Identification
Lead Optimization
Clinical Trials
Phase I
Phase II
Phase III
Phase IV
In Silico vs In vitro
Sources of Pharmacologically Active Compounds
Natural Products
Quantitative Structure Relationship (QSAR)
Docking
Global Docking
Network Pharmacology and Drug Repurposing
Quantitative Systems Pharmacology
Conclusions
References
16: Systems Medicine Applied to Epidemiology
Bioinformatic Tools for Medicine
What Is Systems Biology?
Principles of Network Biology
Systems Medicine, a Novel Branch
Applications of Systems Medicine to Clinical Research
Future Directions and Conclusion
References
17: Genomic Surveillance in Public Health
Genomics in Public Health
Genomic Tools for Epidemiological Surveillance
Genomic and Molecular Research Tools
Culture Methods for Virus
Imaging
High-Performance Sequencing
Virus Outbreaks and Genomic Surveillance
Bacterial Outbreaks and Genomic Surveillance
Mycobacterium Tuberculosis
Clostridium Perfringens
Mycobacterium Leprae
Genomic Surveillance over Other Infectious Diseases
Chronic Diseases and Genomic Surveillance
Cancer
Neurodegenerative Diseases
Cardiovascular Diseases
Other Chronic Diseases
Concluding Remarks
References
Index