Implementation of Personalized Precision Medicine

At the heart of precision medicine lies one concept missing from modern medicine – the unique genetic and biochemical make-up of each individual patient. Implementation of Personalized Precision Medicine: Expanding the Clinical Vision towards Prevention, Early Detection, and Precision Treatment of Disease to Drive Extended Healthspan establishes a landscape of precision medicine geared towards implementation of fully personalized approaches within precision medicine to facilitate prevention and early detection of age-related disease in each individual. This reference details how these lofty goals are now achievable with the science of today and tomorrow and provides the context, thought process and beginning blueprint to guide researchers and clinicians in more effectively considering the prevention and treatment of complex chronic disease.

Uniquely organized, this reference provides insight into creating fully personalized precision medical treatments. Chapters include conventionally considered data such as genetic inherited risk, current epigenetic modifications, and current biochemical markers but also include less conventional food for thought such as microbiome, mitochondrial function, and dna repair. This provocative landscape makes this reference a valuable addition to the literature expanding precision medicine towards personalized chronic disease prevention and treatment.

Implementation of Personalized Precision Medicine
Cover image
Title page
Table of Contents
Copyright
Contributors
Editor’s statement
Chapter 1 Epigenetics and methylation risk scores
Abstract
Keywords
Acknowledgments
The evolution of epigenetics in biomedical research
DNA methylation
Epigenetic technology and its application in health and disease
The emerging field of methylation risk scoring
The power of machine learning to develop predictors of disease
ML-based development of disease classifiers in clinical medicine
Applications in nononcological disease
Applications in aging: The biological clock
The clinical application of MRS in the health care setting
Limitations, challenges, and the future of clinical adoption of MRS at the point of care
References
Chapter 2 Polygenic risk scores: A conceptual overview to add PRS to your clinical toolbox
Abstract
Keywords
Introduction
Association, not causation
Polygenic risk scores come in all sizes
Garbage in, garbage out
Ready for clinical use
Better when we’re together
The promise of PRS
References
Chapter 3 The proteomics revolution: Forging a new path to personalized health care
Abstract
Keywords
Introduction: Proteomics as “the one ring to rule them all”
Why protein networks? And if they are so good, why didn’t it happen earlier?
Proving a breakthrough
Interpreting the results: Expertise in proteomics not required
Traditional diagnostic test development vs the new discipline; what's the difference?
Physiology and utility, the chicken made the egg…
Or is it that the egg made the chicken?
Getting comfortable with the unknown
The few vs the many; reductive vs expansive tensions
Eliminate the immutable
From the vein to the lab: Abuse of blood as a living tissue
Why the cardio-metabolic portfolio bias? Why not cancer?
Where can proteomics win in cancer?
Integrated programmatic planning
Where does it go from here? Bumps on the road to widespread adoption
Overcoming the bias against predicting risk: Prognostic vs diagnostic
Countering the religion about “concentration as truth”
How to redefine analytic validation
Translation into clinical utility and reimbursement by insurers
Leading to a challenge to the diagnostics business model
Winds in our favor—What might accelerate the impact of proteomics in personalized medicine?
Invisible personalized medicine: Proteomics in drug development
The future: Unsupervised learning and AI
Conclusions
References
Chapter 4 Pharmacogenetic clinical implementation
Abstract
Keywords
Introduction
Clinical use and considerations
Psychiatric
Gastrointestinal
Cardiovascular
Respiratory
Multimorbidity
Rheumatology
Infectious disease
The implementation of pharmacogenomics into point of care
Challenges to implementation
Cost savings with implementation of PGx
Conclusion
References
Chapter 5 Seeing clearly to treat precisely: Advances in molecular imaging and theranostics in precision health
Abstract
Keywords
Overview
Imaging across a range of scales
The tools of molecular imaging
Imaging anatomy
Imaging cellular and molecular signatures
Imaging metabolic markers
Imaging cell surface markers
Imaging immune cells for diagnosis and monitoring cellular therapeutics
AI in molecular imaging
Reporter genes
Nanomedicine
Imaging earlier in the disease course
Conclusions
References
Chapter 6 Early quantum computing applications on the path towards precision medicine
Abstract
Keywords
A quantum state of mind
Applying quantum computing in medicine
Genomics and clinical research
Diagnostics
Treatments and interventions
Making it practical and useful
References
Chapter 7 Gene therapy: State of the art precision medicine
Abstract
Keywords
Introduction
Current gene therapy studies in rare diseases
Risk factors and challenges of gene therapy
Immune responses
Targeting the wrong cells
Tumor formation
Ethical concern
High cost of gene therapy
Long-term impact of gene therapy
Multifactorial diseases
The future of gene therapy in rare disease
Antisense oligonucleotides, small molecule drugs, and enzyme replacement therapy
Embryo screening and prenatal gene therapy for rare diseases
Conclusions
References
Chapter 8 Precision mitochondrial medicine: Uncovering pathways across diverse diseases
Abstract
Keywords
Introduction
The landscape of mitochondrial dysfunction
Mitochondrial structure and function
Implications of mitochondrial health in chronic diseases
Precision medicine
Addressing current challenges in progressing precision mitochondrial medicine
State-of-the-art technologies facilitating diagnosis of mitochondrial diseases
Conclusions
References
Chapter 9 Antigen-specific immunotherapy: The ultimate precision medicine for the treatment of autoimmune diseases
Abstract
Keywords
Overview
Introduction
Self/nonself-discrimination
Autoimmune diseases
Current treatments for autoimmune diseases
Antigen-specific immune regulation for the treatment of allergy
Lessons learned on delivery of antigens for autoimmune diseases
Therapeutic approaches suitable for the delivery of intact antigens
Therapeutic approaches based on T cell epitopes
Clinical trials of immunotherapy with apitopes
Precision medicine and antigen-specific immunotherapy
Conclusions
References
Chapter 10 The future of precision diabetes: Digital twin
Abstract
Keywords
Overview of diabetes: Prevalence and global impact
Biomarkers in diabetes: Current landscape
Digital twin technology in diabetes management
Digital twin technology overview
Artificial intelligence in diabetes management
Machine learning and healthcare sensor data
Whole body digital twin technology
Predictor implementation
Sensors and data collection
Twin app for personalized recommendations
Operation and support
Patent and operationalization
Data correlation and recommendations
Glycemic improvements
MAFLD improvement
Cardiovascular improvements
Improvements in complications
Additional improvements
Measures of success and future consolidation
Consolidating gains in future diabetes management
Continuous monitoring and feedback
Dynamic adjustments and early interventions
Patient education and engagement
Integration of advanced technologies
Research and development
Future directions in diabetes prevention and reversal
References
Chapter 11 Precision oncology: Indications and challenges in the implementation of high-throughput sequencing in clinical practice
Abstract
Keywords
Introduction
Precision medicine studies in pan-cancer indications
Molecular tumor board: Definition and objectives
Levels of actionability of molecular alterations
High-throughput sequencing: Clinical applications
Challenges in interpreting NGS
Challenges in implementing NGS on a large-scale basis
Integration of big data in clinical practice_ future perspectives
Conclusion
Annex 1: Case studies
References
Chapter 12 Bringing “precision” to psychiatry: Challenges and promises
Abstract
Keywords
Identification of etiological risk factors
Identification of biological mechanisms underlying etiological risk factors using model systems
Human brain imaging and integration with genetic information
Drug discovery efforts and integration of genetic information
Artificial intelligence (AI) in the implementation of precision psychiatry
Conclusion
References
Chapter 13 Precision medicine in cardiovascular disease
Abstract
Keywords
Precision in cholesterol/atherosclerosis/coronary artery disease
Hypertensive heart disease
Cardiomyopathy/arrhythmias
The return to precision and personalization
Precision medicine in cardiovascular disease
Coronary artery disease (CAD)
Myocardial infarction (MI)
Hypertension
Heart failure
Advancements in technology provide the road to prevention
The specific case for type 2 diabetes
References
Chapter 14 Precision bone health: Genetic testing for low bone density
Abstract
Keywords
Acknowledgments
Overview
Osteoporosis is a major health concern
Bone growth is dynamic
How osteoporosis is diagnosed
Most cases of osteoporosis are undiagnosed
Genetic studies on bone mineral density and osteoporosis
Polygenic risk scores for BMD and osteoporosis
DNA testing to diagnose and treat osteoporosis
The future: P4 medicine for osteoporosis
References
Chapter 15 Functional nutrigenomics: A personalized shift in treating inflammation
Abstract
Keywords
Introduction
The role of nutrition in medicine
MTHFR and HNMT
Clinical considerations
COMT
GSH and Gpx
Clinical considerations
NRF2, KEAP1
Clinical considerations
HO-1
Clinical considerations
Histamine
Histamine intolerance
Clinical considerations
Tools for analysis—Where we’re at
Conclusion
References
Chapter 16 Regulating ferroptosis: Toward precision treatment of dysregulated cell death
Abstract
Keywords
Introduction
Short history of ferroptosis
Iron accumulation
Lipid peroxidation
The process of ferroptosis
Ferroptosis and cancer
Initiation of ferroptosis
Repair mechanism
Natural products to regulate ferroptosis
Andrographis (+)
Apigenin (±)
Artemisinin (+)
Astaxanthin (−)
Baicalein (−)
Brusatol (+)
Curcumin (±)
Epigallocatechin-3-gallate (EGCCG) (−)
Erianin (+)
Kaempferol (−)
Melatonin (−)
N-Acetylcysteine (−)
Piperlongumine (+)
Quercetin (±)
Selenium (−)
Sulforaphane (±)
Vitamin D (±)
Vitamin E (−)
Vitamin K (−)
Patient assessment and treatment options
References
Chapter 17 Precision medicine for brain health and prevention of neurodegenerative/neurocognitive decline
Abstract
Keywords
Acknowledgments
Introduction
Blood work and precision medicine: History and limitations
Neuroimaging as part of precision medicine
Genomics as the ultimate “n” of 1 precision tool
Genetic diseases vs genomic contributing factors
A closer look at “what we are calling Alzheimer’s”
A focus on the role of genomics for improving outcomes in cognitive decline
Digging into cognitive decline and neurodegenerative disease
Contributing factors to cognitive decline
Brain ischemia
Oxidative stress
Inflammation
Nutrient deficiencies
Glutathione and detoxification
Infectious contributing factors
APOE4 and Alzheimer’s
Pharmacogenomics vs genomics for clinical decision support
Utilizing genomics for reversal of cognitive decline
Conclusion
References
Chapter 18 The gut microbiome in personalized precision medicine
Abstract
Keywords
Introduction
Human biome in health and disease
Dietary choices and the microbiome
Current clinical knowledge and interventions
Microbiome analysis tools for precision medicine
Community interconnections in the microbiome
Current advances and future challenges for microbiome-mediated precision medicine
References
Chapter 19 Exposome and detoxification
Abstract
Keywords
Introduction
What is exposure?
The age of plastics
BPA
Air pollution
Genetic susceptibility to air pollution
DNA damage from exposure
CYP/PON1 and organophosphate pesticides
Strategies
Xenobiotic detoxification in humans
Phase 1
Phase 2
Glutathione S-transferases Mu 1 (GSTM1) and theta 1 (GSTT1)
Catechol-O-methyltransferase (COMT)
UGT
Current available strategies
Nutritional pharmacology/toxicology
Toward individualized exposome medicine
Large-scale efforts
Exposomics—Lifecyle medicine
References
Chapter 20 Unraveling the threads of time: Longevity and DNA repair mechanisms
Abstract
Keywords
Introduction
DNA damage and aging
Hallmarks of aging
Genomic instability
Telomere attrition
Epigenetic alterations
Impaired proteostasis
Cellular senescence
Longevity pathways
mTOR
AMPK
Sirtuins and NAD+
IIS (insulin/IGF-1)
DNA repair mechanisms
Base excision repair (BER)
Nucleotide excision repair (NER)
Mismatch repair (MMR)
Double-strand break repair (DSBR)
Telomere maintenance
Interplay of longevity pathways with DNA repair mechanisms
Genetic variants in other key DNA repair tumor suppressor genes
TP53 (p53)
ATM (ataxia telangiectasia mutated)
CHEK2 (checkpoint kinase 2)
RAD51
PARP1 (poly(ADP-ribose) polymerase 1)
Modulation of DNA repair mechanisms
Antioxidants in DNA repair
Longevity pathway nutrients and DNA repair
Nicotinamide adenine dinucleotide (NAD+)
Nicotinamide (NAM)
Quercetin
Omega-3 fatty acids
Emerging technologies in longevity medicine
Clinical practice of longevity medicine
Personalized interventions
Comprehensive health assessments
Precision diagnostics
Therapeutic targeting of aging pathways
Regenerative medicine
Clinical translation challenges
Demographic shifts
Economic considerations
Ethical and cultural perspectives
Technological disruption
Policy and governance
Public perception and education
Longevity resources for research
Conclusion
References
Chapter 21 Considering ethics in precision medicine
Abstract
Keywords
Introduction
Equity in precision health research
Equity in precision health clinical medicine
Autonomy and informed consent
Privacy and confidentiality
Conclusion
References
Chapter 22 Personomics: The personalization of precision medicine
Abstract
Keywords
A patient with heart failure: The traditional approach
A patient with heart failure: The personomics approach
How does personomics differ from patient-centered care?
Personomics: The personalization of precision medicine
References
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Implementation of Personalized Precision Medicine

Expanding the Clinical Vision towards Prevention, Early Detection and Precision Treatment of Disease to Drive Extended Healthspan

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William P. Stanford

Laura Kelly

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