PhenPath

PhenPath maps human phenotypes to genes, biological functions, and pathways to support molecular characterization of disease-associated phenotypes.

Key Features:

• PhenPathDB: Links human genes to phenotypes from the Human Phenotype Ontology (HPO) and OMIM Clinical Synopses, covering 18 OMIM Clinical synopses, 7,137 HPO phenotypes, 4,292 diseases, and 3,446 genes.
• NET-GE (Network-based Gene Enrichment): Associates phenotypes with biological functions and pathways using a network-based gene enrichment method.
• Functional annotations: Enriches phenotypes with Gene Ontology annotations (Biological Process 87.7%, Molecular Function 86.9%, Cellular Component 73.6%).
• Pathway enrichment: Reports phenotype enrichment for KEGG (58.8%) and Reactome (77.8%) pathways.
• PhenPathTOOL: Analyzes user-defined phenotype sets to retrieve shared diseases, genes, and functional terms among phenotypes.

Scientific Applications:

• Molecular characterization of phenotypes: Map phenotypes to genes and functional annotations to interpret biological underpinnings of clinical features.
• Analysis of co-occurring phenotypes: Identify shared diseases, genes, and functional terms among phenotype sets to investigate co-occurrence in patients.
• Hypothesis generation for complex diseases: Detect molecular features common to multiple phenotypes to suggest potential molecular causes of complex disorders.
• Pathway-level interpretation: Use GO, KEGG, and Reactome enrichment to link phenotypes to biological processes and pathways.

Methodology:

PhenPathDB applies NET-GE (Network-based Gene Enrichment) to associate phenotypes with biological functions and pathways using Gene Ontology, KEGG, and Reactome annotations; PhenPathTOOL retrieves shared diseases, genes, and functional terms among user-defined phenotype sets.