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E-book: Advancing Disease Modeling in Animal-Based Research in Support of Precision Medicine: Proceedings of a Workshop

  • Format: 138 pages
  • Pub. Date: 29-May-2018
  • Publisher: National Academies Press
  • Language: eng
  • ISBN-13: 9780309471176
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  • Format: 138 pages
  • Pub. Date: 29-May-2018
  • Publisher: National Academies Press
  • Language: eng
  • ISBN-13: 9780309471176
Other books in subject:

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Precision medicine is focused on the individual and will require the rapid and accurate identification and prioritization of causative factors of disease. To move forward and accelerate the delivery of the anticipated benefits of precision medicine, developing predictable, reproducible, and reliable animal models will be essential. In order to explore the topic of animal-based research and its relevance to precision medicine, the National Academies of Sciences, Engineering, and Medicine convened a 2-day workshop on October 5 and 6, 2017. The workshop was designed to focus on the development, implementation, and interpretation of model organisms to advance and accelerate the field of precision medicine. Participants examined the extent to which next-generation animal models, designed using patient data and phenotyping platforms targeted to reveal and inform disease mechanisms, will be essential to the successful implementation of precision medicine. This publication summarizes the presentations and discussions from the workshop.

Table of Contents



Front Matter 1 Introduction to Precision Medicine and Animal Models 2 Existing Precision Medicine Initiatives 3 The Promise and Perils of Animal Models 4 Reproducibility and Predictivity 5 In Vitro Alternatives to Animal Models 6 Assessing Safety and Toxicology 7 Patient Perspectives 8 Reflections on the Workshop References Appendix A: Agenda Appendix B: Planning Committee Biographies Appendix C: Speaker Biographies
1 Introduction to Precision Medicine and Animal Models
1(15)
Introduction
2(1)
Organization of This Proceedings of a Workshop
3(1)
What Is Precision Medicine and How Did We Get Here?
4(2)
Regulation of Precision Medicine
6(3)
Ethical Considerations of Animal-Based Research
9(3)
Gene-Environment
11(1)
Gene-Lifestyle
12(1)
Longitudinal Data
12(1)
Bioethics, Public Opinion, and Community Advisory Boards
12(4)
2 Existing Precision Medicine Initiatives
16(10)
United States: All of Us
16(4)
United Kingdom: 100,000 Genomes, 18 France: The French Plan for Genomic Medicine
20(2)
Japan: Initiative on Rare and Undiagnosed Diseases
22(1)
World Economic Forum: Center for the Fourth Industrial Revolution
23(3)
3 The Promise and Perils of Animal Models
26(25)
Mouse Models
27(9)
Introduction to Model Organisms
27(2)
International Mouse Phenotyping Consortium
29(1)
Essential Genes
30(2)
Precision Mouse Models
32(4)
Unique Animal-Based Approaches
36(10)
Opossum
36(1)
Precision Pathology
37(3)
Mouse Hospital Co-Clinical Trials
40(3)
Pets with Naturally Occurring Tumors
43(3)
Challenges of Using Animal Models for Precision Medicine
46(5)
Big Data
46(2)
The Animal Rule and Appropriate Modeling
48(3)
4 Reproducibility and Predictivity
51(10)
Translational Stroke Research: The "Worst Practices" of Animal Research
52(1)
Systematic Reviews
53(3)
Reproducibility in Large Shared Datasets
56(2)
The Paradoxes of Precision Medicine
58(3)
5 In Vitro Alternatives To Animal Models
61(8)
iPSCs to Model Chemotherapy-Induced Cardiotoxicity
61(2)
In Vitro Cardiac Disease Models
63(1)
Human Microphysiological Systems
64(2)
Organ-on-a-Chip
65(1)
Organoids
65(1)
Quantitative Systems Pharmacology and Microphysiological Systems
66(3)
Human Microphysiological Systems
67(2)
6 Assessing Safety and Toxicology
69(13)
Patient Susceptibilities in Preclinical Drug Safety Assessment
69(2)
Next-Generation Vivaria
71(1)
Alternative Models
71(1)
Co-expressed Gene Network Analysis as a Bridge for Extrapolation Between Species
71(3)
Using Genetically Diverse Mice to Test Susceptibility to Toxins
74(2)
To Identify Specific Polymorphisms Associated with Xenobiotic Toxicity
75(1)
To Evaluate Biomarker Performance Toward Assessing Human Clinical Adverse Outcomes
76(1)
As a Tool for Population-Based Estimates of Chemical Potency for Risk Assessment
76(1)
Integrating Evidence from Animal and Human Studies
76(6)
7 Patient Perspectives
82(5)
Personalized Medicine Coalition
82(2)
Parkinson's Disease
84(3)
8 Reflections on the Workshop
87(3)
REFERENCES
90(5)
APPENDIXES
A Agenda
95(8)
B Planning Committee Biographies
103(5)
C Speaker Biographies
108