Using phenotypic similarity to improve rare disease identification in PhenomeCentral

<p>Presentation given by Orion Buske at Genome Informatics 2014 in Cambridge, UK. Covers the current performance of patient matching and gene prioritization algorithms in PhenomeCentral.</p

PhenoTips: Patient Phenotyping Software for Clinical and Research Use.

<p>We have developed PhenoTips, a deep phenotyping tool and database, specifically designed for phenotyping patients with genetic disorders. Our tool closely mirrors clinician workflows so as to facilitate the recording of observations made during the patient encounter. Phenotypic information is represented using the Human Phenotype Ontology; however, the complexity of the ontology is hidden behind a user interface, which combines simple selection of common phenotypes with error-tolerant, predictive search of the entire ontology. The software provides a series of features that help reduce the clinician's workload during the clinical examination. Together with standardized phenotypic data, PhenoTips supports entering demographic information, medical history (including prior laboratory results), family history, various measurements, relevant images depicting manifestations of the patient's disorder, genetic tests and their results, as well as additional notes for each of these categories. A pedigree drawing tool which enables the collection of advanced family histories is currently under development. The software automatically plots growth curves for a variety of measurements, selects phenotypes reflecting abnormal measurements, instantly finds Online Mendelian Inheritance in Man (OMIM) diseases that most closely match the phenotypic description, and can suggest additional clinical investigations that can improve the diagnosis.</p> <p>PhenoTips is already used both in research studies and in the clinic, including the phenotyping of patients for the FORGE (Finding Of Rare disease GEnes) Canada project (http://care4rare.ca/), and the Undiagnosed Disease Program at the NIH. Our source code and a demo version of PhenoTips are available at http://phenotips.org.</p

PhenomeCentral: An Integrated Portal for Sharing and Searching Patient Phenotype Data for Rare Genetic Disorders.

<p>The availability of low-cost genome sequencing has allowed for the identification of the molecular cause of hundreds of rare genetic disorders. Solved disorders, however, only represent the “tip of the iceberg”. Because the discovery of disease-causing variants typically requires confirmation of the mutation or gene in multiple unrelated individuals, an even larger number of genetic disorders remain unsolved due to difficulty identifying second families. With many groups now tackling these remaining undiagnosed disorders, which may be present in only a handful of individuals seen at different hospitals and sequenced by different centers, it is critical to establish effective and secure data-sharing techniques that allow clinicians and scientists to identify additional families via phenotype and genotype searches.</p> <p>To address this need, we have developed PhenomeCentral (http://phenomecentral.org), a repository for secure data sharing targeted to the rare disorder community. Each patient record within PhenomeCentral consists of a thorough phenotypic description capturing observed abnormalities as well as relevant absent manifestations, expressed using Human Phenotype Ontology terms. Furthermore, each record can be labeled by the creator as: private ‒ hidden from everyone except the contributor; public ‒ viewable and searchable by all registered users; or matchable ‒ the record cannot be directly viewed or searched, but is reachable via an automated phenotype matching system (following Cafe Variome principles) which informs contributors of the existence of profiles similar to their cases.</p> <p>PhenomeCentral currently incorporates phenotype data for hundreds of patients with rare genetic disorders without a molecular diagnosis, including ongoing submissions from the Canadian CARE for RARE project and the NIH Undiagnosed Diseases Program (UDP). Clinical geneticists and scientists studying rare disorders can request accounts, and new patients can be added either using the PhenoTips User Interface, built into PhenomeCentral, or uploaded in bulk.</p