Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience

Frontiers in Medicine

R. Grace Zhai¹  Peter N. Robinson²  Melissa A. Haendel³  Lynn Carmichael⁴  Joun Park⁵  Yi Zhu⁵  Chong Li⁵  Christofer Bello⁵  Zoraida Diaz-Perez⁵  Jennifer M. Brazill⁵  Cornelius F. Boerkoel⁵  Fayeza S. Malik⁵  Miao He⁶  Nicole Washington⁷  Cheng-Kang Hsieh⁸  Jeremy Elson⁸  Yan Huang⁹  Elise D. Flynn⁹  Camillo Toro⁹  Valerie Maduro⁹  Michele Nehrebecky⁹  Rena Godfrey⁹  Jessica Guzman⁹  Thomas Markello⁹  Christopher Adams⁹  Alexander J. Brandt⁹  Gretchen A. Golas⁹  Karen Xu⁹  Katherine Schaffer⁹  Catherine Groden⁹  Elizabeth Lee⁹  Paul Pemberton⁹  Zaheer Valivullah⁹  Murat Sincan⁹  Megan S. Kane⁹  Colleen Wahl⁹  May Christine V. Malicdan⁹  Amanda E. Links⁹  Mariska Davids⁹  Dimitre Simeonov⁹  William P. Bone⁹  Elise Valkanas⁹  Joie Davis⁹  Timothy Gall^1,10  David Draper^1,10  Lynne A. Wolfe^1,10  David R. Adams^1,10  William A. Gahl^1,10  Cynthia J. Tifft^1,10  Roxanne Fischer^1,10  Damian Smedley^1,12 

[1] Science University, Portland, OR, United States;0The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States;;1Department of Medical Informatics and Clinical Epidemiology, Oregon Health &Appistry, Inc., St. Louis, MO, United States;Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United States;Department of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, PA, United States;Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, United States;MicroSoft Research, Redmond, WA, United States;NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States;National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States;Palmieri Metabolic Disease Laboratory, Children’s Hospital of Philadelphia, Philadelphia, PA, United States;William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom;

关键词: rare disease;    human phenotype ontology;    distributed cognition;    diploid alignment;    glycome;   

DOI  :  10.3389/fmed.2017.00062

来源: DOAJ

【 摘 要 】

Traditionally, the use of genomic information for personalized medical decisions relies on prior discovery and validation of genotype–phenotype associations. This approach constrains care for patients presenting with undescribed problems. The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) hypothesized that defining disease as maladaptation to an ecological niche allows delineation of a logical framework to diagnose and evaluate such patients. Herein, we present the philosophical bases, methodologies, and processes implemented by the NIH UDP. The NIH UDP incorporated use of the Human Phenotype Ontology, developed a genomic alignment strategy cognizant of parental genotypes, pursued agnostic biochemical analyses, implemented functional validation, and established virtual villages of global experts. This systematic approach provided a foundation for the diagnostic or non-diagnostic answers provided to patients and serves as a paradigm for scalable translational research.

【 授权许可】

Unknown