OMIM explorer

OMIM explorer integrates patient phenotype and genotype data with disease catalogs to prioritize rare variant candidates and support clinical evaluation of human genetic disorders.

Key Features:

• Integration with Disease Catalogs: Leverages the Online Mendelian Inheritance in Man (OMIM) database and the Human Phenotype Ontology (HPO) to map diseases and standardized phenotypes.
• Semantic Similarity and Dimensionality Reduction: Applies semantic similarity methods and multidimensional scaling to transform high-dimensional phenotype and genotype data into low-dimensional graphical disease maps.
• Free-text Clinical Note Translation: Translates free-text clinical notes into standardized HPO terms for incorporation into phenotype-driven analyses.
• Phenotype-driven Variant Ranking: Prioritizes and filters rare variant candidates by integrating phenotype and genotype information and updating variant rankings algorithmically.
• Adaptive Disease Gene Discovery: Implements an adaptive approach that leverages patient phenotype data to assist in identifying disease genes.

Scientific Applications:

• Clinical re-analysis of exome data: In a retrospective pilot cohort study at the Baylor Miraca Genetics Laboratory, OMIM explorer assigned clinically reported variants a median rank of 2 and placed causal variants within the top 1% of filtered candidates for cases with molecular diagnoses in OMIM Morbidmap genes, with superior performance reported relative to Phen-Gen, eXtasy, PhenIX, PHIVE, and hiPHIVE.
• Differential diagnosis generation: Produces algorithmically suggested diagnostic alternatives by contextualizing patient phenotypes within disease maps derived from semantic similarity and catalog data.
• Variant prioritization for genomic medicine: Supports diagnostic workflows by integrating phenotype information, catalog data, and genomic knowledge to prioritize candidate variants.

Methodology:

Collapses high-dimensional phenotype and genotype data into graphical disease maps using semantic similarity and multidimensional scaling; translates free-text clinical notes into HPO terms; integrates OMIM and HPO catalogs; and filters and ranks variants with phenotype-driven, adaptive gene-discovery approaches.