title: PhenomeCentral: a portal for phenotypic and genotypic matchmaking of patients with rare genetic diseases.
abstract: The discovery of disease-causing mutations typically requires confirmation of the variant or gene in multiple unrelated individuals, and a large number of rare genetic diseases remain unsolved due to difficulty identifying second families. To enable the secure sharing of case records by clinicians and rare disease scientists, we have developed the PhenomeCentral portal (https://phenomecentral.org). Each record includes a phenotypic description and relevant genetic information (exome or candidate genes). PhenomeCentral identifies similar patients in the database based on semantic similarity between clinical features, automatically prioritized genes from whole-exome data, and candidate genes entered by the users, enabling both hypothesis-free and hypothesis-driven matchmaking. Users can then contact other submitters to follow up on promising matches. PhenomeCentral incorporates data for over 1,000 patients with rare genetic diseases, contributed by the FORGE and Care4Rare Canada projects, the US NIH Undiagnosed Diseases Program, the EU Neuromics and ANDDIrare projects, as well as numerous independent clinicians and scientists. Though the majority of these records have associated exome data, most lack a molecular diagnosis. PhenomeCentral has already been used to identify causative mutations for several patients, and its ability to find matching patients and diagnose these diseases will grow with each additional patient that is entered.
authors.affiliation: Department of Computer Science, University of Toronto, Toronto, Canada.|Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada.|Centre for Computational Medicine, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Orion J
authors.initials: OJ
authors.lastname: Buske
authors.affiliation: Department of Computer Science, University of Toronto, Toronto, Canada.|Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada.|Centre for Computational Medicine, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Marta
authors.initials: M
authors.lastname: Girdea
authors.affiliation: Centre for Computational Medicine, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Sergiu
authors.initials: S
authors.lastname: Dumitriu
authors.affiliation: Centre for Computational Medicine, The Hospital for Sick Children, Toronto, Canada.|Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Bailey
authors.initials: B
authors.lastname: Gallinger
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
authors.forename: Taila
authors.initials: T
authors.lastname: Hartley
authors.affiliation: Centre for Computational Medicine, The Hospital for Sick Children, Toronto, Canada.|Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: Trang
authors.affiliation: Centre for Computational Medicine, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Andriy
authors.initials: A
authors.lastname: Misyura
authors.affiliation: Department of Computer Science, University of Toronto, Toronto, Canada.
authors.forename: Tal
authors.initials: T
authors.lastname: Friedman
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
authors.forename: Chandree
authors.initials: C
authors.lastname: Beaulieu
authors.affiliation: Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland.
authors.forename: William P
authors.initials: WP
authors.lastname: Bone
authors.affiliation: Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Links
authors.affiliation: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Washington
authors.affiliation: Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Haendel
authors.affiliation: Institute for Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Robinson
authors.affiliation: Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland.
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
authors.affiliation: Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Adams
authors.affiliation: Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland.
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.affiliation: Department of Computer Science, University of Toronto, Toronto, Canada.|Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada.|Centre for Computational Medicine, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Brudno
mesh_terms: D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D033181:Information Dissemination / Q000379:methods*; D010641:Phenotype; D035583:Rare Diseases / Q000235:genetics*; D012984:Software; D014584:User-Computer Interface; D064878:Web Browser
keywords: HPO; Matchmaker Exchange; deep phenotyping; patient matchmaking; semantic similarity