@article{feb66234ec844bcd805a826ffa77f873,
title = "Defining disease, diagnosis, and translational medicine within a homeostatic perturbation paradigm: The National Institutes of Health undiagnosed diseases program experience",
abstract = "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.",
keywords = "Diploid alignment, Distributed cognition, Glycome, Human phenotype ontology, Rare disease",
author = "Timothy Gall and Elise Valkanas and Christofer Bello and Thomas Markello and Christopher Adams and Bone, {William P.} and Brandt, {Alexander J.} and Brazill, {Jennifer M.} and Lynn Carmichael and Mariska Davids and Joie Davis and Zoraida Diaz-Perez and David Draper and Jeremy Elson and Flynn, {Elise D.} and Rena Godfrey and Catherine Groden and Hsieh, {Cheng Kang} and Roxanne Fischer and Golas, {Gretchen A.} and Jessica Guzman and Yan Huang and Kane, {Megan S.} and Elizabeth Lee and Chong Li and Links, {Amanda E.} and Valerie Maduro and Malicdan, {May Christine V.} and Malik, {Fayeza S.} and Michele Nehrebecky and Joun Park and Paul Pemberton and Katherine Schaffer and Dimitre Simeonov and Murat Sincan and Damian Smedley and Zaheer Valivullah and Colleen Wahl and Nicole Washington and Wolfe, {Lynne A.} and Karen Xu and Yi Zhu and Gahl, {William A.} and Tifft, {Cynthia J.} and Camillo Toro and Adams, {David R.} and Miao He and Robinson, {Peter N.} and Haendel, {Melissa A.} and {Grace Zhai}, R. and Boerkoel, {Cornelius F.}",
note = "Publisher Copyright: {\textcopyright} 2017 Gall, Valkanas, Bello, Markello, Adams, Bone, Brandt, Brazill, Carmichael, Davids, Davis, Diaz-Perez, Draper, Elson, Flynn, Godfrey, Groden, Hsieh, Fischer, Golas, Guzman, Huang, Kane, Lee, Li, Links, Maduro, Malicdan, Malik, Nehrebecky, Park, Pemberton, Schaffer, Simeonov, Sincan, Smedley, Valivullah, Wahl, Washington, Wolfe, Xu, Zhu, Gahl, Tifft, Toro, Adams, He, Robinson, Haendel, Zhai and Boerkoel.",
year = "2017",
doi = "10.3389/fmed.2017.00062",
language = "English (US)",
volume = "4",
journal = "Frontiers in Medicine",
issn = "2296-858X",
publisher = "Frontiers Media S. A.",
number = "MAY",
}