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This article is part of the supplement: Eighth International Conference on Bioinformatics (InCoB2009):Computational Biology

Open Access Proceedings

A sequence-based hybrid predictor for identifying conformationally ambivalent regions in proteins

Yu-Cheng Liu1, Meng-Han Yang2, Win-Li Lin1, Chien-Kang Huang4* and Yen-Jen Oyang235*

Author Affiliations

1 Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, Republic of China

2 Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan, Republic of China

3 Graduate Institutes of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan, Republic of China

4 Department of Engineering Science and Ocean Engineering, National Taiwan University, Taipei 106, Taiwan, Republic of China

5 Center for Systems Biology and Bioinformatics, National Taiwan University, Taipei, Taiwan, Republic of China

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BMC Genomics 2009, 10(Suppl 3):S22  doi:10.1186/1471-2164-10-S3-S22

Published: 3 December 2009

Abstract

Background

Proteins are dynamic macromolecules which may undergo conformational transitions upon changes in environment. As it has been observed in laboratories that protein flexibility is correlated to essential biological functions, scientists have been designing various types of predictors for identifying structurally flexible regions in proteins. In this respect, there are two major categories of predictors. One category of predictors attempts to identify conformationally flexible regions through analysis of protein tertiary structures. Another category of predictors works completely based on analysis of the polypeptide sequences. As the availability of protein tertiary structures is generally limited, the design of predictors that work completely based on sequence information is crucial for advances of molecular biology research.

Results

In this article, we propose a novel approach to design a sequence-based predictor for identifying conformationally ambivalent regions in proteins. The novelty in the design stems from incorporating two classifiers based on two distinctive supervised learning algorithms that provide complementary prediction powers. Experimental results show that the overall performance delivered by the hybrid predictor proposed in this article is superior to the performance delivered by the existing predictors. Furthermore, the case study presented in this article demonstrates that the proposed hybrid predictor is capable of providing the biologists with valuable clues about the functional sites in a protein chain. The proposed hybrid predictor provides the users with two optional modes, namely, the high-sensitivity mode and the high-specificity mode. The experimental results with an independent testing data set show that the proposed hybrid predictor is capable of delivering sensitivity of 0.710 and specificity of 0.608 under the high-sensitivity mode, while delivering sensitivity of 0.451 and specificity of 0.787 under the high-specificity mode.

Conclusion

Though experimental results show that the hybrid approach designed to exploit the complementary prediction powers of distinctive supervised learning algorithms works more effectively than conventional approaches, there exists a large room for further improvement with respect to the achieved performance. In this respect, it is of interest to investigate the effects of exploiting additional physiochemical properties that are related to conformational ambivalence. Furthermore, it is of interest to investigate the effects of incorporating lately-developed machine learning approaches, e.g. the random forest design and the multi-stage design. As conformational transition plays a key role in carrying out several essential types of biological functions, the design of more advanced predictors for identifying conformationally ambivalent regions in proteins deserves our continuous attention.