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Published on: July 14, 2015
DEPCOD: a tool to detect and visualize co-evolution of protein domains
Fei Ji1,2, Gracia Bonilla1,2, Rustem Krykbaev1
1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
Analyzing protein domain conservation patterns reveals functional links between non-homologous proteins. The new DEPCOD web server (DEtection of Phylogenetically COrrelated Domains) aids in discovering these evolutionary relationships.
Area of Science:
- Evolutionary biology
- Bioinformatics
- Computational biology
Background:
- Proteins with similar evolutionary conservation patterns often share cellular functions or interactions.
- Previous methods analyzed whole proteins, overlooking domain-specific evolutionary pressures.
- Protein domains, rather than whole proteins, may provide a more accurate unit for detecting functional associations.
Purpose of the Study:
- To develop and present a novel web server, DEPCOD (DEtection of Phylogenetically COrrelated Domains), for identifying functional relationships between protein domains.
- To leverage phylogenetic sequence profiling at the domain level for enhanced detection of functional associations.
- To provide an interactive tool for exploring evolutionary conservation patterns of protein domains.
Main Methods:
- Analysis of sequence conservation patterns across the entire tree of life for individual protein domains from various organisms.
- Development of the DEPCOD web server to accept pre-defined domains or user sequences as queries.
- Comparison of conservation patterns on evolutionary scales including the whole tree of life and eukaryotic genomes.
Main Results:
- DEPCOD successfully detects functional relationships between non-homologous protein domains that were missed by whole-protein analysis.
- The web server displays top similarities, known protein interactions, shared complexes, and pathway enrichment for detected domains.
- Detailed visualization of the sources contributing to detected similarities is provided.
Conclusions:
- Analyzing protein domains as units of evolution significantly improves the detection of functional associations.
- DEPCOD offers a powerful, interactive platform for discovering novel functional links between protein domains based on phylogenetic profiles.
- The tool facilitates a deeper understanding of protein function and evolution by focusing on domain-level conservation patterns.
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