GeneBridge

GeneBridge annotates gene functions and predicts module-module associations using Gene-Module Association Determination (G-MAD) and Module-Module Association Determination (M-MAD) applied to multispecies expression compendia.

Key Features:

• Gene-Module Association Determination (G-MAD): Associates genes with specific biological processes or modules using multispecies expression data.
• Module-Module Association Determination (M-MAD): Predicts associations between biological modules to reveal module connectivity, including mitochondria with proteasome functions, histone demethylation pathways, and ribosomes with lipid biosynthesis.
• Multispecies expression compendia: Integrates expression data encompassing over 300,000 samples from humans, mice, rats, flies, worms, and yeast.
• Novel function and module component discovery: Identifies novel gene functions (for example, DDT in mitochondrial respiration and WDFY4 in T cell activation) and suggests new components for modules such as cholesterol biosynthesis.
• Tissue-specific functional delineation: Resolves tissue-specific gene roles, exemplified by EHHADH in liver and kidney and SLC6A1 in brain and liver.
• Systems-level integration: Combines G-MAD and M-MAD outputs to link genes, modules, phenotypes, and diseases for systems biology analyses.

Scientific Applications:

• Gene function annotation: Assigns genes to biological processes and modules across species using expression compendia.
• Module interaction mapping: Maps module-module associations to uncover networks of cellular processes.
• Novel discovery: Enables discovery of previously uncharacterized gene functions and additional module components.
• Tissue-specific inference: Infers context-dependent gene roles in specific tissues such as liver, kidney, and brain.
• Comparative functional genomics: Facilitates cross-species analyses by leveraging large multispecies datasets.
• Linking to phenotypes and diseases: Supports identification of connections among genes, biological modules, phenotypes, and diseases.

Methodology:

Applies G-MAD to associate genes with modules and M-MAD to predict module-module associations using multispecies expression compendia validated across over 300,000 samples from humans, mice, rats, flies, worms, and yeast.