DEPCOD

DEPCOD detects co-evolutionary relationships between protein domains by using normalized phylogenetic sequence profiling to identify functional associations among non-homologous proteins across the tree of life and within eukaryotic genomes.

Key Features:

• Normalized Phylogenetic Sequence Profiling: Employs normalized phylogenetic sequence profiling to analyze sequence conservation patterns at the domain level.
• Domain-Level Analysis: Uses protein domains as the primary unit of analysis to account for differential selective pressures on multi-domain proteins.
• Evolutionary Scales: Performs analyses across the entire tree of life and specifically within eukaryotic genomes to detect scale-dependent conservation patterns.
• Similarity Scoring and Annotation: Identifies top similarity hits between domain profiles and annotates hits with known protein interactions, shared complexes, and pathway enrichment.
• Functional Relationship Detection: Reveals potential functional associations and co-evolutionary links among often non-homologous domains based on shared evolutionary trajectories.

Scientific Applications:

• Functional association discovery: Detects co-evolving domains to infer functional associations between non-homologous proteins.
• Protein interaction and complex inference: Highlights domains that co-evolve with known interaction partners or components of shared complexes.
• Comparative genomics: Identifies conserved domains and lineage-specific conservation or loss across diverse organisms.
• Pathway enrichment and functional module analysis: Supports pathway enrichment analyses by linking co-evolving domains to biological pathways and modules.

Methodology:

Computes normalized phylogenetic sequence profiles by analyzing domain-level sequence conservation patterns across a comprehensive set of organisms, compares profiles across the tree of life and within eukaryotes to identify domains with similar evolutionary trajectories, and reports top similarity scores annotated with known protein interactions, shared complexes, and pathway enrichment.