ArticleFrontiers in medicine2017
Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience.
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Article in Frontiers in medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Curation and expansion of Human Phenotype Ontology for defined groups of inborn errors of immunity.The Journal of allergy and clinical immunology · 2022Pooled it
- Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features.Journal of medical genetics · 2019Trial
- Development of self-phenotyping tools to empower patients and improve diagnostics.EBioMedicine · 2025Article
- Leveraging clinical intuition to improve accuracy of phenotype-driven prioritization.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Loss of Fic causes progressive neurodegeneration in a Drosophila model of hereditary spastic paraplegia.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Accelerating rare disease detection: an experience of multidisciplinary team model in undiagnosed diseases program in a children's hospital.Frontiers in public health · 2024Article
- PheNominal: an EHR-integrated web application for structured deep phenotyping at the point of care.BMC medical informatics and decision making · 2022Article
- Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Article
- The practice of genomic medicine: A delineation of the process and its governing principles.Frontiers in medicine · 2022Article
- Advances in mouse genetics for the study of human disease.Human molecular genetics · 2021Review
- The Increasing Impact of Translational Research in the Molecular Diagnostics of Neuromuscular Diseases.International journal of molecular sciences · 2021Review
- The case for open science: rare diseases.JAMIA open · 2020Review
- The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species.Nucleic acids research · 2020Article
- Comparison of Causative Variant Prioritization Tools Using Next-generation Sequencing Data in Japanese Patients with Mendelian Disorders.Yonago acta medica · 2019Article
- Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.Nucleic acids research · 2019Article
- Representing glycophenotypes: semantic unification of glycobiology resources for disease discovery.Database : the journal of biological databases and curation · 2019Review
- Classification, Ontology, and Precision Medicine.The New England journal of medicine · 2018Review
- High-throughput mouse phenomics for characterizing mammalian gene function.Nature reviews. Genetics · 2018Review
- Plain-language medical vocabulary for precision diagnosis.Nature genetics · 2018Article
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Authors and funding
51 authors.
Timothy GallNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Elise ValkanasNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Christofer BelloDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United States.
Thomas MarkelloNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Christopher AdamsNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
William P BoneNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Alexander J BrandtNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Jennifer M BrazillDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United States.
Lynn CarmichaelAppistry, Inc., St. Louis, MO, United States.
Mariska DavidsNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Joie DavisNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Zoraida Diaz-PerezDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United States.
David DraperNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Jeremy ElsonMicroSoft Research, Redmond, WA, United States.
Elise D FlynnNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Rena GodfreyNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Catherine GrodenNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Cheng-Kang HsiehMicroSoft Research, Redmond, WA, United States.
Roxanne FischerNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States.
Gretchen A GolasNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Jessica GuzmanNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Yan HuangNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Megan S KaneNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Elizabeth LeeNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Chong LiDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United States.
Amanda E LinksNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Valerie MaduroNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
May Christine V MalicdanNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Fayeza S MalikDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United States.
Michele NehrebeckyNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Joun ParkDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United States.
Paul PembertonNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Katherine SchafferNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Dimitre SimeonovNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Murat SincanNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Damian SmedleyWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Zaheer ValivullahNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Colleen WahlNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Nicole WashingtonEnvironmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, United States.
Lynne A WolfeNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Karen XuNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Yi ZhuDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United States.
William A GahlNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Cynthia J TifftNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Camillo ToroNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
David R AdamsNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Miao HePalmieri Metabolic Disease Laboratory, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Peter N RobinsonThe Jackson Laboratory for Genomic Medicine, Farmington, CT, United States.
Melissa A HaendelDepartment of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, United States.
R Grace ZhaiDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, United States.
Cornelius F BoerkoelNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, United States.
Funding
NHGRI/DIR Clinical Support ServicesZIDHG200352 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SOLOMON, BENJAMIN · 2009 to 2025
$182.8MHuman Biochemical GeneticsZIAHG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2025
$72.6MThe Monarch Initiative: Linking Diseases to Model Organism ResourcesR24OD011883 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HAENDEL, MELISSA A, MUNGALL, CHRISTOPHER J · 2012 to 2024
$16.0MHuman Biochemical GeneticsZ01HG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM ALLEN · 2003 to 2008
$10.2MFunctional Interaction of GBAS and SLC41A2 in Drosophila models for UDP_755R21GM119018 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ZHAI, RONG GRACE · 2016 to 2019
$675kEXPANDING AND ENHANCING THE GENE EXPRESSION DATABASEF32HG000215 · NHGRI · JACKSON LABORATORY · PI CORRADI, JOHN P · 2000 to 2000
$10kIntramural NIH HHS Z01 HG000215NHGRI NIH HHS F32 HG000215NHGRI NIH HHS HHSN268201300036CNHGRI NIH HHS HHSN268201300038CNHGRI NIH HHS HHSN268201400033CNHLBI NIH HHS HHSN268201600043CNIGMS NIH HHS R21 GM119018NIH HHS R24 OD011883
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.
Indexed as
diploid alignmentdistributed cognitionglycomehuman phenotype ontologyrare disease
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