The case for open science: rare diseases

Yaffa R Rubinstein¹, Peter N Robinson², William A Gahl³, Paul Avillach⁴, Gareth Baynam⁵, Helene Cederroth⁶, Rebecca M Goodwin⁷, Stephen C Groft⁸, Mats G Hansson⁹, Nomi L Harris¹⁰, Vojtech Huser¹¹, Deborah Mascalzoni¹², Julie A McMurry¹³, Matthew Might¹⁴, Christoffer Nellaker¹⁵, Barend Mons¹⁶, Dina N Paltoo⁷, Jonathan Pevsner¹⁷, Manuel Posada¹⁸, Alison P Rockett-Frase¹⁹, Marco Roos²⁰, Tamar B Rubinstein²¹, Domenica Taruscio²², Esther van Enckevort²³, Melissa A Haendel¹³

Affiliations

¹ Special Volunteer in the Office of Strategic Initiatives, National Library of Medicine, Bethesda, Maryland, USA.
² The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
³ Undiagnosed Diseases Program and Office of the Clinical Director, National Human Genome Research Institute (NHGRI), National Institutes of Health, Bethesda, Maryland, USA.
⁴ Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.
⁵ Western Australian Register of Developmental Anomalies and Telethon Kids Institute, Perth, Australia.
⁶ Wilhelm Foundation, Brottby, Sweden.
⁷ Department of Health and Human Services, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
⁸ NCATS, National Institutes of Health, Bethesda, Maryland, USA.
⁹ Center for Research Ethics and Bioethics, Uppsala Universitet, Uppsala, Sweden.
¹⁰ Department of Environmental Genomics & System Biology, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
¹¹ Department of Health and Human Services, NCBI, National Institutes of Health, Bethesda, Maryland, USA.
¹² Center for Research Ethics and Bioethics, Uppsala University, Sweden and EURAC Research, Bolzano, Italy.
¹³ Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA.
¹⁴ Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁵ Nuffield Department of Women's and Reproductive Health, Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
¹⁶ Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
¹⁷ Department of Neurology, Kennedy Krieger Institute and Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
¹⁸ Rare Diseases Research Institute & CIBERER, Instituto de Salud Carlos III, Madrid, Spain.
¹⁹ Joshua Frase Foundation, Ponte Vedra Beach, Florida, USA.
²⁰ Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
²¹ Children Hospital at Montefiore/Albert Einstein College of Medicine-Pediatrics, Bronx, New York, USA.
²² National Centre for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy.
²³ Department of Genetics, University Medical Center Groningen, University of Groningen, Leiden, Netherlands.

PMID: 33426479
PMCID: PMC7660964
DOI: 10.1093/jamiaopen/ooaa030

Review

The case for open science: rare diseases

Yaffa R Rubinstein et al. JAMIA Open. 2020.

. 2020 Sep 11;3(3):472-486.

doi: 10.1093/jamiaopen/ooaa030. eCollection 2020 Oct.

Authors

Affiliations

¹ Special Volunteer in the Office of Strategic Initiatives, National Library of Medicine, Bethesda, Maryland, USA.
² The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
³ Undiagnosed Diseases Program and Office of the Clinical Director, National Human Genome Research Institute (NHGRI), National Institutes of Health, Bethesda, Maryland, USA.
⁴ Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.
⁵ Western Australian Register of Developmental Anomalies and Telethon Kids Institute, Perth, Australia.
⁶ Wilhelm Foundation, Brottby, Sweden.
⁷ Department of Health and Human Services, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
⁸ NCATS, National Institutes of Health, Bethesda, Maryland, USA.
⁹ Center for Research Ethics and Bioethics, Uppsala Universitet, Uppsala, Sweden.
¹⁰ Department of Environmental Genomics & System Biology, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
¹¹ Department of Health and Human Services, NCBI, National Institutes of Health, Bethesda, Maryland, USA.
¹² Center for Research Ethics and Bioethics, Uppsala University, Sweden and EURAC Research, Bolzano, Italy.
¹³ Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA.
¹⁴ Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁵ Nuffield Department of Women's and Reproductive Health, Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
¹⁶ Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
¹⁷ Department of Neurology, Kennedy Krieger Institute and Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
¹⁸ Rare Diseases Research Institute & CIBERER, Instituto de Salud Carlos III, Madrid, Spain.
¹⁹ Joshua Frase Foundation, Ponte Vedra Beach, Florida, USA.
²⁰ Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
²¹ Children Hospital at Montefiore/Albert Einstein College of Medicine-Pediatrics, Bronx, New York, USA.
²² National Centre for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy.
²³ Department of Genetics, University Medical Center Groningen, University of Groningen, Leiden, Netherlands.

PMID: 33426479
PMCID: PMC7660964
DOI: 10.1093/jamiaopen/ooaa030

Abstract

The premise of Open Science is that research and medical management will progress faster if data and knowledge are openly shared. The value of Open Science is nowhere more important and appreciated than in the rare disease (RD) community. Research into RDs has been limited by insufficient patient data and resources, a paucity of trained disease experts, and lack of therapeutics, leading to long delays in diagnosis and treatment. These issues can be ameliorated by following the principles and practices of sharing that are intrinsic to Open Science. Here, we describe how the RD community has adopted the core pillars of Open Science, adding new initiatives to promote care and research for RD patients and, ultimately, for all of medicine. We also present recommendations that can advance Open Science more globally.

Keywords: FAIR data; common data elements; data standards; ontology; open science; rare disease patients.

Published by Oxford University Press on behalf of the American Medical Informatics Association 2020.

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Figures

**Figure 1.**
Rare diseases. (A) RDs are individually rare but collectively impact ∼10% of the population. Here, RDs are represented in the classic aphorism, “When you hear hoofbeats, think of horses, not zebras”—in other words, look for the most common disease that matches the symptoms, not the rarest one. It was originally used by Theodore Woodward, professor at the University of Maryland School of Medicine in the 1940s. (B) Defining RDs requires carefully matching a patient’s spectrum of phenotypes with the phenotypic profile of candidate diseases, here represented by a single color-feature. Each zebra (patient) has a constellation of phenotypes that may match none, some (dashed lines), or all (solid lines) of the phenotypes of other zebras. The diagnosis of RDs often involves recognition of phenotypic patterns and is aided by computational phenotype analysis.

**Figure 2.**
Phenopackets provide a mechanism for structured, de-identified, patient-level phenotype data sharing for computational use across the globe and in different information systems. Image credit: GA4GH Communications Team.

See this image and copyright information in PMC

References

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The case for open science: rare diseases

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The case for open science: rare diseases

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