Defining disease, diagnosis, and translational medicine within a homeostatic perturbation paradigm

The National Institutes of Health undiagnosed diseases program experience

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, Jeremy Elson, Elise D. Flynn, Rena Godfrey, Catherine Groden, Cheng Kang Hsieh, Roxanne Fischer, Gretchen A. Golas & 31 others 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, Karen Xu, Yi Zhu, William A. Gahl, Cynthia J. Tifft, Camillo Toro, David R. Adams, Miao He, Peter N. Robinson, Melissa Haendel, R. Grace Zhai, Cornelius F. Boerkoel

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Article number62
JournalFrontiers in Medicine
Volume4
Issue numberMAY
DOIs
StatePublished - Jan 1 2017

Fingerprint

Translational Medical Research
National Institutes of Health (U.S.)
Genetic Association Studies
Patient Care
Genotype
Phenotype

Keywords

  • Diploid alignment
  • Distributed cognition
  • Glycome
  • Human phenotype ontology
  • Rare disease

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Defining disease, diagnosis, and translational medicine within a homeostatic perturbation paradigm : The National Institutes of Health undiagnosed diseases program experience. / Gall, Timothy; Valkanas, Elise; Bello, Christofer; Markello, Thomas; Adams, Christopher; Bone, William P.; Brandt, Alexander J.; Brazill, Jennifer M.; Carmichael, Lynn; Davids, Mariska; Davis, Joie; Diaz-Perez, Zoraida; Draper, David; Elson, Jeremy; Flynn, Elise D.; Godfrey, Rena; Groden, Catherine; Hsieh, Cheng Kang; Fischer, Roxanne; Golas, Gretchen A.; Guzman, Jessica; Huang, Yan; Kane, Megan S.; Lee, Elizabeth; Li, Chong; Links, Amanda E.; Maduro, Valerie; Malicdan, May Christine V.; Malik, Fayeza S.; Nehrebecky, Michele; Park, Joun; Pemberton, Paul; Schaffer, Katherine; Simeonov, Dimitre; Sincan, Murat; Smedley, Damian; Valivullah, Zaheer; Wahl, Colleen; Washington, Nicole; Wolfe, Lynne A.; Xu, Karen; Zhu, Yi; Gahl, William A.; Tifft, Cynthia J.; Toro, Camillo; Adams, David R.; He, Miao; Robinson, Peter N.; Haendel, Melissa; Grace Zhai, R.; Boerkoel, Cornelius F.

In: Frontiers in Medicine, Vol. 4, No. MAY, 62, 01.01.2017.

Research output: Contribution to journalArticle

Gall, T, Valkanas, E, Bello, C, Markello, T, Adams, C, Bone, WP, Brandt, AJ, Brazill, JM, Carmichael, L, Davids, M, Davis, J, Diaz-Perez, Z, Draper, D, Elson, J, Flynn, ED, Godfrey, R, Groden, C, Hsieh, CK, Fischer, R, Golas, GA, Guzman, J, Huang, Y, Kane, MS, Lee, E, Li, C, Links, AE, Maduro, V, Malicdan, MCV, Malik, FS, Nehrebecky, M, Park, J, Pemberton, P, Schaffer, K, Simeonov, D, Sincan, M, Smedley, D, Valivullah, Z, Wahl, C, Washington, N, Wolfe, LA, Xu, K, Zhu, Y, Gahl, WA, Tifft, CJ, Toro, C, Adams, DR, He, M, Robinson, PN, Haendel, M, Grace Zhai, R & Boerkoel, CF 2017, 'Defining disease, diagnosis, and translational medicine within a homeostatic perturbation paradigm: The National Institutes of Health undiagnosed diseases program experience', Frontiers in Medicine, vol. 4, no. MAY, 62. https://doi.org/10.3389/fmed.2017.00062
Gall, Timothy ; Valkanas, Elise ; Bello, Christofer ; Markello, Thomas ; Adams, Christopher ; Bone, William P. ; Brandt, Alexander J. ; Brazill, Jennifer M. ; Carmichael, Lynn ; Davids, Mariska ; Davis, Joie ; Diaz-Perez, Zoraida ; Draper, David ; Elson, Jeremy ; Flynn, Elise D. ; Godfrey, Rena ; Groden, Catherine ; Hsieh, Cheng Kang ; Fischer, Roxanne ; Golas, Gretchen A. ; Guzman, Jessica ; Huang, Yan ; Kane, Megan S. ; Lee, Elizabeth ; Li, Chong ; Links, Amanda E. ; Maduro, Valerie ; Malicdan, May Christine V. ; Malik, Fayeza S. ; Nehrebecky, Michele ; Park, Joun ; Pemberton, Paul ; Schaffer, Katherine ; Simeonov, Dimitre ; Sincan, Murat ; Smedley, Damian ; Valivullah, Zaheer ; Wahl, Colleen ; Washington, Nicole ; Wolfe, Lynne A. ; Xu, Karen ; Zhu, Yi ; Gahl, William A. ; Tifft, Cynthia J. ; Toro, Camillo ; Adams, David R. ; He, Miao ; Robinson, Peter N. ; Haendel, Melissa ; Grace Zhai, R. ; Boerkoel, Cornelius F. / Defining disease, diagnosis, and translational medicine within a homeostatic perturbation paradigm : The National Institutes of Health undiagnosed diseases program experience. In: Frontiers in Medicine. 2017 ; Vol. 4, No. MAY.
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