PhenoExam

PhenoExam performs phenotype enrichment and differential analysis of gene sets to identify significant phenotypic and disease associations and to compare phenotype similarities across multiple annotation databases for human and mouse genes.

Key Features:

• Phenotype and Disease Enrichment Analysis: Performs enrichment analysis on input gene sets using phenotype and disease annotations to identify significantly associated phenotypic terms and gene-to-disease associations.
• Statistical Phenotype Similarity Measurement: Computes statistical measures of phenotype similarity between gene sets to quantify shared and distinct phenotypic profiles.
• Differential Phenotype Detection: Detects phenotypic and disease terms that differ significantly between gene sets across integrated annotation databases to support differential diagnosis and refinement of genetic panels.

Scientific Applications:

• Gene-to-disease validation: Validates novel gene-to-disease associations using enrichment and phenotypic projection analyses, with validation reported via simulations and real-case applications.
• Differential diagnosis and panel refinement: Identifies differential phenotypes between gene sets to aid differential diagnosis and refine genetic testing panels.
• Comparative disease analysis: Applied to early-onset Parkinson’s disease and dystonia gene sets to reveal phenotype-level similarities and differences.
• Validation of predicted disease genes: Validated computationally predicted candidate genes for epilepsy by uncovering phenotype links across annotation databases.

Methodology:

Integrates multiple annotation databases — Human Phenotype Ontology (HPO), Mouse Genome Database (MGD), CRISPRbrain, Comparative Toxicogenomics Database (CTD), ClinGen, Clinical Genome Resource (CGI), OrphaNET, UniProt, PsyGeNET, and Genomics England Panel App — performs analyses on human and mouse genes, and projects disease-causing genes into their annotation-based phenotypic spaces.