DAR

DAR maps disease-associated enzymes onto Reactome pathways to link genes, variants, and diseases for analysis of molecular mechanisms of human genetic diseases.

Key Features:

• Data integration: Integrates variant- and disease-associated entries from OMIM, Humsavar, ClinVar, and Monarch to link enzymes with genetic disease annotations.
• Coverage: Associates 1,494 human enzymes with 2,539 genetic diseases, 75% of which are classified as rare using Orphanet codes.
• Ontology standardization: Uses the Mondo ontology to standardize disease names into specific codes to enable computational associations.
• Reactome mapping: Maps disease-associated enzymes onto Reactome pathways to create enzyme–pathway–disease associations.
• Disease categorization: Enables categorization of monogenic and polygenic diseases based on specific pathway interactions.
• Molecular context: Identifies other molecules involved in affected pathways to provide molecular context for disease mechanisms.
• Computational associations: Establishes associations between genes, variants, diseases, and their impacts on biological processes.

Scientific Applications:

• Mechanistic interpretation: Elucidate links between genetic diseases and Reactome-defined biological processes to investigate molecular mechanisms.
• Disease landscape analysis: Dissect the landscape of human genetic diseases by mapping enzyme-disease relationships across pathways.
• Pathway-centered classification: Provide a pathway-centered classification of monogenic and polygenic diseases.
• Identification of molecular players: Highlight additional molecules in pathways that may contribute to disease etiology or progression.

Methodology:

Integrates data from OMIM, Humsavar, ClinVar, and Monarch; standardizes disease terms using the Mondo ontology; maps enzymes onto Reactome pathways; and computes associations among genes, variants, diseases, and biological processes.