Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Medicine |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmed.2017.00062/full |
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| author | Timothy Gall Timothy Gall Elise Valkanas Christofer Bello Thomas Markello Christopher Adams William P. Bone Alexander J. Brandt Jennifer M. Brazill Lynn Carmichael Mariska Davids Joie Davis Zoraida Diaz-Perez David Draper David Draper Jeremy Elson Elise D. Flynn Rena Godfrey Catherine Groden Cheng-Kang Hsieh Roxanne Fischer Gretchen A. Golas Jessica Guzman Yan Huang Megan S. Kane Elizabeth Lee Chong Li Amanda E. Links Valerie Maduro May Christine V. Malicdan Fayeza S. Malik Michele Nehrebecky Joun Park Paul Pemberton Katherine Schaffer Dimitre Simeonov Murat Sincan Damian Smedley Zaheer Valivullah Colleen Wahl Nicole Washington Lynne A. Wolfe Lynne A. Wolfe Karen Xu Yi Zhu William A. Gahl William A. Gahl Cynthia J. Tifft Cynthia J. Tifft Camillo Toro David R. Adams David R. Adams Miao He Miao He Peter N. Robinson Melissa A. Haendel R. Grace Zhai Cornelius F. Boerkoel |
| author_facet | Timothy Gall Timothy Gall Elise Valkanas Christofer Bello Thomas Markello Christopher Adams William P. Bone Alexander J. Brandt Jennifer M. Brazill Lynn Carmichael Mariska Davids Joie Davis Zoraida Diaz-Perez David Draper David Draper Jeremy Elson Elise D. Flynn Rena Godfrey Catherine Groden Cheng-Kang Hsieh Roxanne Fischer Gretchen A. Golas Jessica Guzman Yan Huang Megan S. Kane Elizabeth Lee Chong Li Amanda E. Links Valerie Maduro May Christine V. Malicdan Fayeza S. Malik Michele Nehrebecky Joun Park Paul Pemberton Katherine Schaffer Dimitre Simeonov Murat Sincan Damian Smedley Zaheer Valivullah Colleen Wahl Nicole Washington Lynne A. Wolfe Lynne A. Wolfe Karen Xu Yi Zhu William A. Gahl William A. Gahl Cynthia J. Tifft Cynthia J. Tifft Camillo Toro David R. Adams David R. Adams Miao He Miao He Peter N. Robinson Melissa A. Haendel R. Grace Zhai Cornelius F. Boerkoel |
| author_sort | Timothy Gall |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T08:50:47Z |
| format | Article |
| id | doaj.art-af6f4d04ca6b42d0ad0634041b7f5a4c |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-11T08:50:47Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-af6f4d04ca6b42d0ad0634041b7f5a4c2022-12-22T01:14:01ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2017-05-01410.3389/fmed.2017.00062261607Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program ExperienceTimothy Gall0Timothy Gall1Elise Valkanas2Christofer Bello3Thomas Markello4Christopher Adams5William P. Bone6Alexander J. Brandt7Jennifer M. Brazill8Lynn Carmichael9Mariska Davids10Joie Davis11Zoraida Diaz-Perez12David Draper13David Draper14Jeremy Elson15Elise D. Flynn16Rena Godfrey17Catherine Groden18Cheng-Kang Hsieh19Roxanne Fischer20Gretchen A. Golas21Jessica Guzman22Yan Huang23Megan S. Kane24Elizabeth Lee25Chong Li26Amanda E. Links27Valerie Maduro28May Christine V. Malicdan29Fayeza S. Malik30Michele Nehrebecky31Joun Park32Paul Pemberton33Katherine Schaffer34Dimitre Simeonov35Murat Sincan36Damian Smedley37Zaheer Valivullah38Colleen Wahl39Nicole Washington40Lynne A. Wolfe41Lynne A. Wolfe42Karen Xu43Yi Zhu44William A. Gahl45William A. Gahl46Cynthia J. Tifft47Cynthia J. Tifft48Camillo Toro49David R. Adams50David R. Adams51Miao He52Miao He53Peter N. Robinson54Melissa A. Haendel55R. Grace Zhai56Cornelius F. Boerkoel57NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United StatesAppistry, Inc., St. Louis, MO, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United StatesMicroSoft Research, Redmond, WA, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesMicroSoft Research, Redmond, WA, United StatesNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesEnvironmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United StatesPalmieri Metabolic Disease Laboratory, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, PA, United States0The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States1Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, United StatesDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United StatesNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United StatesTraditionally, 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.http://journal.frontiersin.org/article/10.3389/fmed.2017.00062/fullrare diseasehuman phenotype ontologydistributed cognitiondiploid alignmentglycome |
| spellingShingle | Timothy Gall Timothy Gall Elise Valkanas Christofer Bello Thomas Markello Christopher Adams William P. Bone Alexander J. Brandt Jennifer M. Brazill Lynn Carmichael Mariska Davids Joie Davis Zoraida Diaz-Perez David Draper David Draper Jeremy Elson Elise D. Flynn Rena Godfrey Catherine Groden Cheng-Kang Hsieh Roxanne Fischer Gretchen A. Golas Jessica Guzman Yan Huang Megan S. Kane Elizabeth Lee Chong Li Amanda E. Links Valerie Maduro May Christine V. Malicdan Fayeza S. Malik Michele Nehrebecky Joun Park Paul Pemberton Katherine Schaffer Dimitre Simeonov Murat Sincan Damian Smedley Zaheer Valivullah Colleen Wahl Nicole Washington Lynne A. Wolfe Lynne A. Wolfe Karen Xu Yi Zhu William A. Gahl William A. Gahl Cynthia J. Tifft Cynthia J. Tifft Camillo Toro David R. Adams David R. Adams Miao He Miao He Peter N. Robinson Melissa A. Haendel R. Grace Zhai Cornelius F. Boerkoel Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience Frontiers in Medicine rare disease human phenotype ontology distributed cognition diploid alignment glycome |
| title | Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience |
| title_full | Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience |
| title_fullStr | Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience |
| title_full_unstemmed | Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience |
| title_short | Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience |
| title_sort | defining disease diagnosis and translational medicine within a homeostatic perturbation paradigm the national institutes of health undiagnosed diseases program experience |
| topic | rare disease human phenotype ontology distributed cognition diploid alignment glycome |
| url | http://journal.frontiersin.org/article/10.3389/fmed.2017.00062/full |
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