ArticlePloS one2010
Accurate protein structure annotation through competitive diffusion of enzymatic functions over a network of local evolutionary similarities.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Variants inGenes & diseases · 2026Article
- Functional variants identify sex-specific genes and pathways in Alzheimer's Disease.Nature communications · 2023Article
- Graph-based information diffusion method for prioritizing functionally related genes in protein-protein interaction networks.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2020Article
- Multimodal network diffusion predicts future disease-gene-chemical associations.Bioinformatics (Oxford, England) · 2019Article
- Article
- Prediction and experimental validation of enzyme substrate specificity in protein structures.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Accounting for epistatic interactions improves the functional analysis of protein structures.Bioinformatics (Oxford, England) · 2013Article
- Recent advances in functional region prediction by using structural and evolutionary information - Remaining problems and future extensions.Computational and structural biotechnology journal · 2013Review
- Function prediction from networks of local evolutionary similarity in protein structure.BMC bioinformatics · 2013Article
- ETAscape: analyzing protein networks to predict enzymatic function and substrates in Cytoscape.Bioinformatics (Oxford, England) · 2012Article
- The use of evolutionary patterns in protein annotation.Current opinion in structural biology · 2012Review
- Mapping the mutual information network of enzymatic families in the protein structure to unveil functional features.PloS one · 2012Article
- Evolutionary trace for prediction and redesign of protein functional sites.Methods in molecular biology (Clifton, N.J.) · 2012Article
- Protein function prediction: towards integration of similarity metrics.Current opinion in structural biology · 2011Review
- Prediction and redesign of protein-protein interactions.Progress in biophysics and molecular biologyReview
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6 authors.
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Abstract
High-throughput Structural Genomics yields many new protein structures without known molecular function. This study aims to uncover these missing annotations by globally comparing select functional residues across the structural proteome. First, Evolutionary Trace Annotation, or ETA, identifies which proteins have local evolutionary and structural features in common; next, these proteins are linked together into a proteomic network of ETA similarities; then, starting from proteins with known functions, competing functional labels diffuse link-by-link over the entire network. Every node is thus assigned a likelihood z-score for every function, and the most significant one at each node wins and defines its annotation. In high-throughput controls, this competitive diffusion process recovered enzyme activity annotations with 99% and 97% accuracy at half-coverage for the third and fourth Enzyme Commission (EC) levels, respectively. This corresponds to false positive rates 4-fold lower than nearest-neighbor and 5-fold lower than sequence-based annotations. In practice, experimental validation of the predicted carboxylesterase activity in a protein from Staphylococcus aureus illustrated the effectiveness of this approach in the context of an increasingly drug-resistant microbe. This study further links molecular function to a small number of evolutionarily important residues recognizable by Evolutionary Tracing and it points to the specificity and sensitivity of functional annotation by competitive global network diffusion. A web server is at http://mammoth.bcm.tmc.edu/networks.
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