GUILDify

GUILDify prioritizes disease-gene associations and characterizes gene phenotypes by applying guilt-by-association analyses on protein-protein interaction networks.

Key Features:

• Network Topology-Based Prioritization: Integrates four distinct network-based disease-gene prioritization algorithms that score gene products based on interaction network topology and relevance to keywords or phenotypic traits.
• Integration with BIANA knowledge base: Queries the BIANA knowledge base to retrieve aggregated data from major public repositories for initial phenotype-gene associations.
• Free-text phenotype retrieval: Uses free text searches across biological databases to obtain gene products associated with user-specified keywords or phenotypes.
• Species-specific and user-specified gene support: Operates on species-specific interaction networks and accepts user-specified genes rather than restricting to predefined phenotypes.
• Seed-protein initialization: Employs retrieved gene products as seed proteins within species-specific protein-protein interaction networks to drive network propagation and prioritization.
• Drug-target ranking for repurposing: Ranks drug targets within the network to identify potential links between existing pharmaceuticals and new disease contexts.
• Detection of genes in complex disorders: Highlights genes implicated in complex genetic disorders that may not coincide with known linkage intervals by leveraging network topology.

Scientific Applications:

• Phenotype-wide disease-gene analysis: Applied to analyze dozens of disease phenotypes to identify and prioritize candidate disease-associated genes.
• Identification of non-obvious associations: Reveals disease-gene associations that were not part of the initial seed set used in the analysis.
• Case studies in specific diseases: Has been used to investigate top-ranking genes in Alzheimer's disease (AD), diabetes, and AIDS.
• Drug repurposing investigations: Supports linking existing drug targets to new disease contexts through network-based ranking.

Methodology:

GUILDify queries integrated biological databases (via free text searches in the BIANA knowledge base) to retrieve gene products that serve as seed proteins in species-specific protein-protein interaction networks, and then calculates gene relevance using four network-based prioritization algorithms that apply guilt-by-association principles based on proximity and interactions within the network.