domainsignatures

domainsignatures performs pathway enrichment analysis for sparsely annotated gene lists by comparing InterPro domain signatures to assign genes to known pathways and functional classifications.

Key Features:

• InterPro Domain Signature Comparison: Uses InterPro-encoded domain architectures to compare domain signatures between candidate gene lists and known gene sets such as KEGG to assign functional annotations.
• Simulation-Based Validation: Validated by simulation studies that generate test gene lists by randomly selecting pathway-associated genes, removing them from their original pathways, and introducing non-pathway genes as noise to assess recovery of pathway membership.
• High Sensitivity: Demonstrates high sensitivity for detecting pathway enrichment in gene lists with sparse annotations based on simulation and biological data analyses.
• R Implementation: Implemented as an R package for integration into computational workflows.

Scientific Applications:

• High-throughput functional genomics: Assigns candidate genes from functional screens and gene expression analyses with limited annotations to KEGG pathways or other functional collections using domain signatures.

Methodology:

Compares InterPro domain architectures of candidate genes to domain signatures of known gene sets (e.g., KEGG pathways) to assign functional annotations and evaluates performance via simulation experiments that randomly select pathway genes, remove them from their pathways, and add non-pathway genes as noise; implemented in R.