a statistical model of protein sequence similarity and function similarity reveals overly-specific function predictions一个统计模型的蛋白质序列相似性和功能相似揭示过于具体功能预测.pdfVIP

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a statistical model of protein sequence similarity and function similarity reveals overly-specific function predictions一个统计模型的蛋白质序列相似性和功能相似揭示过于具体功能预测.pdf

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a statistical model of protein sequence similarity and function similarity reveals overly-specific function predictions一个统计模型的蛋白质序列相似性和功能相似揭示过于具体功能预测

A Statistical Model of Protein Sequence Similarity and Function Similarity Reveals Overly-Specific Function Predictions Brenton Louie1,2., Roger Higdon1,2., Eugene Kolker1,2,3* 1 Bioinformatics and High-throughput Analysis Laboratory, Seattle Children’s Research Institute, Seattle, Washington, United States of America, 2 Predictive Analytics, Seattle Children’s Hospital, University of Washington School of Medicine, Seattle, Washington, United States of America, 3 Biomedical and Health Informatics Division, Department of Medical Education and Biomedical Informatics, University of Washington School of Medicine, Seattle, Washington, United States of America Abstract Background: Predicting protein function from primary sequence is an important open problem in modern biology. Not only are there many thousands of proteins of unknown function, current approaches for predicting function must be improved upon. One problem in particular is overly-specific function predictions which we address here with a new statistical model of the relationship between protein sequence similarity and protein function similarity. Methodology: Our statistical model is based on sets of proteins with experimentally validated functions and numeric measures of function specificity and function similarity derived from the Gene Ontology. The model predicts the similarity of function between two proteins given their amino acid sequence similarity measured by statistics from the BLAST sequence alignment algorithm. A novel aspect of our model is that it predicts the degree of function similarity shared between two proteins over a continuous range of sequence similarity, facilitating prediction of function with an appropriate level of specificity. Significance: Our model shows nearly exact function similarity for proteins with high sequence similarity (bit score .244.7, e-value .1e262, non-redundant NCBI protein d