DECO

DECO integrates de novo mutations, rare case/control variants, and omics data within a gene-set framework to identify enriched biological pathways or cell types and to prioritize additional risk genes underlying complex diseases.

Key Features:

• Joint Analysis Framework: Integrates de novo mutations, rare case/control variants, and omics data within gene-sets for combined analysis.
• Gene-Set Enrichment Testing: Tests enrichment of gene-sets directly within its statistical model to identify pathways or cell types enriched for rare damaging variants.
• Risk Gene Prioritization: Leverages identified enriched gene-sets to rank existing genes and prioritize additional risk genes.
• Comparative Performance: Simulation studies demonstrated improved performance compared to methods that rely solely on variant data.
• Application to Complex Diseases: Applied to diverse disorders, including neuropsychiatric disorders, to enhance candidate gene discovery.

Scientific Applications:

• Complex disease genetics: Identifies enriched biological pathways and prioritizes risk genes contributing to complex genetic architectures.
• Neuropsychiatric disorder studies: Integrates multi-source rare variant and omics data to highlight pathways and candidate genes relevant to neuropsychiatric conditions.
• Schizophrenia research: Prioritizes new candidate genes associated with schizophrenia through gene-set-aware analysis of rare variants and omics information.

Methodology:

Combines de novo mutations, rare case/control variants, and omics data within a gene-set-aware statistical model that tests gene-set enrichment and ranks/prioritizes genes.