PhenoDis

PhenoDis provides a curated database for phenotype-dependent analysis and diagnosis in precision medicine focusing on rare cardiac diseases.

Key Features:

• Disease coverage: Integrates 214 rare cardiac diseases from Orphanet and 94 diseases from OMIM (Online Mendelian Inheritance in Man).
• Manual literature annotation: Each disease entry is manually annotated using biomedical literature to provide detailed symptom descriptions.
• Human Phenotype Ontology: Employs 2247 distinct Human Phenotype Ontology (HPO) terms for precise phenotypic characterization.
• Symptom spectrum: Captures a broad spectrum of symptoms with cardiovascular manifestations comprising 28%, neurological 11.5%, and metabolic 6% of annotated symptoms.
• Symptom frequency documentation: Records the frequency of each symptom within specific diseases and notes that 71% of annotated symptoms occur in less than half of affected patients.
• Genetic and imprinting information: Documents disease-associated genes and imprinting information for annotated diseases.
• ClinVar variant annotations: Includes pathogenic and likely pathogenic genetic variant annotations from ClinVar for 206 diseases.
• Support for computational prediction: Provides detailed phenotypic and genetic annotations to support computer-based prediction models for disease and causal gene identification.

Scientific Applications:

• Phenotype-driven diagnosis: Enables phenotype-dependent analysis and diagnosis in precision medicine for rare cardiac diseases.
• Variant interpretation and gene discovery: Supports identification and interpretation of disease-causing genes and ClinVar-listed pathogenic and likely pathogenic variants.
• Computational model development: Serves as a reference dataset for developing and evaluating computer-based prediction models and decision support systems for inherited diseases.

Methodology:

Integration of disease entries from Orphanet and OMIM, manual annotation from biomedical literature using 2247 HPO terms, documentation of symptom frequencies and disease-associated genes and imprinting, and inclusion of ClinVar pathogenic and likely pathogenic variant annotations for 206 diseases.