title: GeneYenta: a phenotype-based rare disease case matching tool based on online dating algorithms for the acceleration of exome interpretation.
abstract: Advances in next-generation sequencing (NGS) technologies have helped reveal causal variants for genetic diseases. In order to establish causality, it is often necessary to compare genomes of unrelated individuals with similar disease phenotypes to identify common disrupted genes. When working with cases of rare genetic disorders, finding similar individuals can be extremely difficult. We introduce a web tool, GeneYenta, which facilitates the matchmaking process, allowing clinicians to coordinate detailed comparisons for phenotypically similar cases. Importantly, the system is focused on phenotype annotation, with explicit limitations on highly confidential data that create barriers to participation. The procedure for matching of patient phenotypes, inspired by online dating services, uses an ontology-based semantic case matching algorithm with attribute weighting. We evaluate the capacity of the system using a curated reference data set and 19 clinician entered cases comparing four matching algorithms. We find that the inclusion of clinician weights can augment phenotype matching.
authors.affiliation: Graduate Program in Bioinformatics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Gottlieb
authors.forename: David J
authors.initials: DJ
authors.lastname: Arenillas
authors.forename: Savanie
authors.initials: S
authors.lastname: Maithripala
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Maurer
authors.forename: Maja
authors.initials: M
authors.lastname: Tarailo Graovac
authors.forename: Linlea
authors.initials: L
authors.lastname: Armstrong
authors.forename: Millan
authors.initials: M
authors.lastname: Patel
authors.forename: Clara
authors.initials: C
authors.lastname: van Karnebeek
authors.forename: Wyeth W
authors.initials: WW
authors.lastname: Wasserman
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D059472:Exome; D063990:Gene Ontology; D056726:Genetic Association Studies / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020407:Internet; D010641:Phenotype; D035583:Rare Diseases / Q000175:diagnosis* / Q000235:genetics*; D012984:Software
keywords: rare genetic disorders; phenotype annotation; case matching; human phenotype ontology