Automatic annotation of protein motif function with Gene Ontology terms

BackgroundConserved protein sequence motifs are short stretches of amino acid sequence patterns that potentially encode the function of proteins. Several sequence pattern searching algorithms and programs exist foridentifying candidate protein motifs at the whole genome level. However, amuch needed and importanttask is to determine the functions of the newly identified protein motifs. The Gene Ontology (GO) project is an endeavor to annotate the function of genes or protein sequences with terms from a dynamic, controlled vocabulary and these annotations serve well as a knowledge base.ResultsThis paperpresents methods to mine the GO knowledge base and use the association between the GO terms assigned to a sequence and the motifs matched by the same sequence as evidence for predicting the functions of novel protein motifs automatically. The task of assigning GO terms to protein motifsis viewed as both a binary classification and information retrieval problem, where PROSITE motifs are used as samples for mode training and functional prediction. The mutual information of a motif and aGO term association isfound to be a very useful feature. We take advantageof the known motifs to train a logistic regression classifier, which allows us to combine mutual information with other frequency-based features and obtain a probability of correctassociation. The trained logistic regression model has intuitively meaningful and logically plausible parameter values, and performs very well empirically according to our evaluation criteria.ConclusionsIn this research, different methods for automatic annotation of protein motifs have been investigated. Empirical result demonstrated that the methods have a great potential for detecting and augmenting information about thefunctions of newly discovered candidate protein motifs.

[1]  Andrea Califano,et al.  SPLASH: structural pattern localization analysis by sequential histograms , 2000, Bioinform..

[2]  I. Rigoutsos,et al.  Dictionary-driven protein annotation. , 2002, Nucleic acids research.

[3]  David R. Gilbert,et al.  Approaches to the Automatic Discovery of Patterns in Biosequences , 1998, J. Comput. Biol..

[4]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[5]  Amos Bairoch,et al.  The PROSITE database, its status in 2002 , 2002, Nucleic Acids Res..

[6]  Aris Floratos,et al.  Combinatorial pattern discovery in biological sequences: The TEIRESIAS algorithm [published erratum appears in Bioinformatics 1998;14(2): 229] , 1998, Bioinform..

[7]  Andrew P. Bradley,et al.  The use of the area under the ROC curve in the evaluation of machine learning algorithms , 1997, Pattern Recognit..

[8]  Jun S. Liu,et al.  Detecting subtle sequence signals: a Gibbs sampling strategy for multiple alignment. , 1993, Science.

[9]  Jeffrey T. Chang,et al.  Associating genes with gene ontology codes using a maximum entropy analysis of biomedical literature. , 2002, Genome research.

[10]  John B. Anderson,et al.  CDD: a curated Entrez database of conserved domain alignments , 2003, Nucleic Acids Res..

[11]  Jérôme Gouzy,et al.  ProDom and ProDom-CG: tools for protein domain analysis and whole genome comparisons , 2000, Nucleic Acids Res..

[12]  J Schultz,et al.  SMART, a simple modular architecture research tool: identification of signaling domains. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[13]  David W. Hosmer,et al.  Applied Logistic Regression , 1991 .

[14]  Thomas M. Cover,et al.  Elements of Information Theory , 2005 .

[15]  Eric R. Ziegel,et al.  The Elements of Statistical Learning , 2003, Technometrics.

[16]  Avi Shoshan,et al.  Large-scale protein annotation through gene ontology. , 2002, Genome research.

[17]  J. Schug,et al.  Predicting gene ontology functions from ProDom and CDD protein domains. , 2002, Genome research.

[18]  Yiming Yang,et al.  An Evaluation of Statistical Approaches to Text Categorization , 1999, Information Retrieval.

[19]  Shmuel Pietrokovski,et al.  Increased coverage of protein families with the Blocks Database servers , 2000, Nucleic Acids Res..

[20]  J. Blake,et al.  Creating the Gene Ontology Resource : Design and Implementation The Gene Ontology Consortium 2 , 2001 .

[21]  C. Patten,et al.  Finding Patterns in Biological Sequences , 2000 .