A visual and curatorial approach to clinical variant prioritization and disease gene discovery in genome-wide diagnostics

Genome Medicine
Regis A JamesChad A Shaw

Abstract

Genome-wide data are increasingly important in the clinical evaluation of human disease. However, the large number of variants observed in individual patients challenges the efficiency and accuracy of diagnostic review. Recent work has shown that systematic integration of clinical phenotype data with genotype information can improve diagnostic workflows and prioritization of filtered rare variants. We have developed visually interactive, analytically transparent analysis software that leverages existing disease catalogs, such as the Online Mendelian Inheritance in Man database (OMIM) and the Human Phenotype Ontology (HPO), to integrate patient phenotype and variant data into ranked diagnostic alternatives. Our tool, "OMIM Explorer" ( http://www.omimexplorer.com ), extends the biomedical application of semantic similarity methods beyond those reported in previous studies. The tool also provides a simple interface for translating free-text clinical notes into HPO terms, enabling clinical providers and geneticists to contribute phenotypes to the diagnostic process. The visual approach uses semantic similarity with multidimensional scaling to collapse high-dimensional phenotype and genotype data from an individual into a graphical ...Continue Reading

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Citations

Dec 3, 2016·Nucleic Acids Research·Sebastian KöhlerPeter N Robinson
Jan 26, 2017·BioTechniques·Mahjoubeh Jalali Sefid Dashti, Junaid Gamieldien
Jan 29, 2018·BMC Bioinformatics·Daniel KoilePatricio Yankilevich
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Jan 1, 2020·BMC Medical Genomics·Dvir DaharySimon Fishilevich
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Jan 22, 2021·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Avi FellnerLina Basel-Salmon
Aug 7, 2020·American Journal of Human Genetics·Peter N RobinsonDamian Smedley

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Methods Mentioned

BETA
genotyping
MDS
exome sequencing

Software Mentioned

RStudio Shiny
Lark
ATO
ClinVar
Node
Shiny
SIFT
Morbidmap
eXtasy
Exomiser

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