Phen2Gene

Phen2Gene prioritizes candidate disease genes from patient phenotypes using Human Phenotype Ontology (HPO) terms to support genetic diagnosis of rare diseases.

Key Features:

• Probabilistic Model Integration: Integrates HPO annotations with gene-disease associations and gene-gene interactions within a probabilistic framework to compute gene prioritization scores.
• HPO2Gene Knowledgebase (H2GKB): Accesses the HPO2Gene Knowledgebase (H2GKB) which provides weighted and ranked gene lists corresponding to each HPO term.
• PhenoPackets Support: Accepts PhenoPackets phenotype descriptions conforming to GA4GH standards as input for prioritization.
• Real-Time Prioritization: Performs rapid ranking of candidate causal genes from patient-specific HPO terms or PhenoPacket descriptions.
• Benchmarking Data: Validated with benchmarking datasets including 197 patients from 76 publications and de-identified HPO-term data from 85 patients at CHOP.

Scientific Applications:

• Rare disease diagnosis: Supports clinical identification of candidate causal genes for rare and undiagnosed diseases using phenotype-driven prioritization.
• Gene-disease research: Aids researchers in exploring and prioritizing gene-disease associations derived from patient phenotypes.
• Phenotype-driven genetic interpretation: Enables rapid analysis of complex phenotype data encoded as HPO terms or PhenoPackets for downstream genetic interpretation.

Methodology:

Accesses H2GKB to retrieve weighted and ranked gene lists for input HPO terms or PhenoPacket descriptions and applies a probabilistic model that integrates HPO annotations, gene-disease associations, and gene-gene interactions to calculate and rank candidate genes.