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Bioinformatics Advance Access published online on February 2, 2005
Bioinformatics, doi:10.1093/bioinformatics/bti303
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Bioinformatics © Oxford University Press 2005; all rights reserved.
Received November 15, 2004
Revised January 7, 2005
Accepted January 27, 2005

Article

An improved hidden Markov model for transmembrane protein detection and topology prediction and its applications to complete genomes

Robel Y. Kahsay 1, Guang Gao 1, and Li Liao 2*

1 Delaware Biotechnology Institute, Newark, DE 19715
2 Delaware Biotechnology Institute, Newark, DE 19715; Department of Computer & Information Sciences, University of Delaware, 103 Smith Hall, Newark, DE 19716

* To whom correspondence should be addressed.
Li Liao, E-mail: lliao{at}cis.udel.edu


  Abstract

Motivation: Knowledge of the transmembrane helical topology can help identify binding sites and infer functions for membrane proteins. However, because membrane proteins are hard to solubilize and purify, only a very small amount of membrane proteins have structure and topology experimentally determined. This has motivated various computational methods for predicting the topology of membrane proteins.

Results: We present an improved hidden Markov model, TMMOD, for the identification and topology prediction of transmembrane proteins. Our model uses TMHMM (Sonnhammer et al., 1998) as a prototype, but differs from TMHMM by the architecture of the submodels for loops on both sides of the membrane and also by the model training procedure. In cross-validation experiments using a set of 83 transmembrane proteins with known topology, TMMOD outperformed TMHMM and other existing methods, with an accuracy of 89% for both topology and locations. In another experiment using a separate set of 160 transmembrane proteins, TMMOD has 84% for topology and 89% for locations. When utilized for identifying transmembrane proteins from non-transmembrane proteins, particularly signal peptides, TMMOD has consistently fewer false positives than TMHMM does. Application of TMMOD to a collection of complete genomes shows that the number of predicted membrane proteins accounts for roughly 20-30% of all genes in those genomes, and that the topology where both the N and C termini are in the cytoplasm is dominant in these organisms except for C. elegans.

Availability: http://liao.cis.udel.edu/website/servers/TMMOD/.


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