title: AudioGene: predicting hearing loss genotypes from phenotypes to guide genetic screening.
abstract: Autosomal dominant nonsyndromic hearing loss (ADNSHL) is a common and often progressive sensory deficit. ADNSHL displays a high degree of genetic heterogeneity and varying rates of progression. Accurate, comprehensive, and cost-effective genetic testing facilitates genetic counseling and provides valuable prognostic information to affected individuals. In this article, we describe the algorithm underlying AudioGene, a software system employing machine-learning techniques that utilizes phenotypic information derived from audiograms to predict the genetic cause of hearing loss in persons segregating ADNSHL. Our data show that AudioGene has an accuracy of 68% in predicting the causative gene within its top three predictions, as compared with 44% for a majority classifier. We also show that AudioGene remains effective for audiograms with high levels of clinical measurement noise. We identify audiometric outliers for each genetic locus and hypothesize that outliers may reflect modifying genetic effects. As personalized genomic medicine becomes more common, AudioGene will be increasingly useful as a phenotypic filter to assess pathogenicity of variants identified by massively parallel sequencing.
authors.affiliation: Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Taylor
authors.forename: Adam P
authors.initials: AP
authors.lastname: Deluca
authors.forename: A Eliot
authors.initials: AE
authors.lastname: Shearer
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hildebrand
authors.forename: E Ann
authors.initials: EA
authors.lastname: Black-Ziegelbein
authors.forename: V Nikhil
authors.initials: VN
authors.lastname: Anand
authors.forename: Christina M
authors.initials: CM
authors.lastname: Sloan
authors.forename: Robert W
authors.initials: RW
authors.lastname: Eppsteiner
authors.forename: Todd E
authors.initials: TE
authors.lastname: Scheetz
authors.forename: Patrick L M
authors.initials: PL
authors.lastname: Huygen
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.forename: Terry A
authors.initials: TA
authors.lastname: Braun
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Casavant
mesh_terms: D000465:Algorithms; D001299:Audiometry; D005820:Genetic Testing; D005838:Genotype; D034381:Hearing Loss / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D020407:Internet; D010641:Phenotype; D015203:Reproducibility of Results; D012984:Software