NegGOA: negative GO annotations selection using ontology structure.
Predicting the biological functions of proteins is one of the key challenges in the post-genomic era. Computational models have demonstrated the utility of applying machine learning methods to predict protein function. Most prediction methods explicitly require a set of negative examples-proteins that are known not carrying out a particular function. However, Gene Ontology (GO) almost always only provides the knowledge that proteins carry out a particular function, and functional annotations of proteins are incomplete. GO structurally organizes more than tens of thousands GO terms and a protein is annotated with several (or dozens) of these terms. For these reasons, the negative examples of a protein can greatly help distinguishing true positive examples of the protein from such a large candidate GO space.



In this paper, we present a novel approach (called NegGOA) to select negative examples. Specifically, NegGOA takes advantage of the ontology structure, available annotations and potentiality of additional annotations of a protein to choose negative examples of the protein. We compare NegGOA with other negative examples selection algorithms and find that NegGOA produces much fewer false negatives than them. We incorporate the selected negative examples into an efficient function prediction model to predict the functions of proteins in Yeast, Human, Mouse and Fly. NegGOA also demonstrates improved accuracy than these comparing algorithms across various evaluation metrics. In addition, NegGOA is less suffered from incomplete annotations of proteins than these comparing methods.



The Matlab and R codes are available at https://sites.google.com/site/guoxian85/neggoa



gxyu@swu.edu.cn



Supplementary data are available at Bioinformatics online.
College of Computer and Information Science, Southwest University, Chongqing 400715, China.
Guangyuan
G
Fu
College of Computer and Information Science, Southwest University, Chongqing 400715, China.
Jun
J
Wang
Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, Changchun 130012, China.
Bo
B
Yang
College of Computer and Information Science, Southwest University, Chongqing 400715, China Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, Changchun 130012, China.
Guoxian
G
Yu
D000465:Algorithms; D000818:Animals; D019295:Computational Biology; D063990:Gene Ontology; D006801:Humans; D051379:Mice; D011506:Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae
D011506:Proteins