A Combined Transmembrane Topology and Signal Peptide Prediction Method. Käll, L., Krogh, A., & Sonnhammer, E. L. L Journal of Molecular Biology, 338(5):1027–1036, May, 2004.
A Combined Transmembrane Topology and Signal Peptide Prediction Method [link]Paper  doi  abstract   bibtex   
An inherent problem in transmembrane protein topology prediction and signal peptide prediction is the high similarity between the hydrophobic regions of a transmembrane helix and that of a signal peptide, leading to cross-reaction between the two types of predictions. To improve predictions further, it is therefore important to make a predictor that aims to discriminate between the two classes. In addition, topology information can be gained when successfully predicting a signal peptide leading a transmembrane protein since it dictates that the N terminus of the mature protein must be on the non-cytoplasmic side of the membrane. Here, we present Phobius, a combined transmembrane protein topology and signal peptide predictor. The predictor is based on a hidden Markov model (HMM) that models the different sequence regions of a signal peptide and the different regions of a transmembrane protein in a series of interconnected states. Training was done on a newly assembled and curated dataset. Compared to TMHMM and SignalP, errors coming from cross-prediction between transmembrane segments and signal peptides were reduced substantially by Phobius. False classifications of signal peptides were reduced from 26.1% to 3.9% and false classifications of transmembrane helices were reduced from 19.0% to 7.7%. Phobius was applied to the proteomes of Homo sapiens and Escherichia coli. Here we also noted a drastic reduction of false classifications compared to TMHMM/SignalP, suggesting that Phobius is well suited for whole-genome annotation of signal peptides and transmembrane regions. The method is available at http://phobius.cgb.ki.se/ as well as at http://phobius.binf.ku.dk/
@article{kall_combined_2004,
	title = {A {Combined} {Transmembrane} {Topology} and {Signal} {Peptide} {Prediction} {Method}},
	volume = {338},
	issn = {0022-2836},
	url = {http://www.sciencedirect.com/science/article/pii/S0022283604002943},
	doi = {10.1016/j.jmb.2004.03.016},
	abstract = {An inherent problem in transmembrane protein topology prediction and signal peptide prediction is the high similarity between the hydrophobic regions of a transmembrane helix and that of a signal peptide, leading to cross-reaction between the two types of predictions. To improve predictions further, it is therefore important to make a predictor that aims to discriminate between the two classes. In addition, topology information can be gained when successfully predicting a signal peptide leading a transmembrane protein since it dictates that the N terminus of the mature protein must be on the non-cytoplasmic side of the membrane. Here, we present Phobius, a combined transmembrane protein topology and signal peptide predictor. The predictor is based on a hidden Markov model (HMM) that models the different sequence regions of a signal peptide and the different regions of a transmembrane protein in a series of interconnected states. Training was done on a newly assembled and curated dataset. Compared to TMHMM and SignalP, errors coming from cross-prediction between transmembrane segments and signal peptides were reduced substantially by Phobius. False classifications of signal peptides were reduced from 26.1\% to 3.9\% and false classifications of transmembrane helices were reduced from 19.0\% to 7.7\%. Phobius was applied to the proteomes of Homo sapiens and Escherichia coli. Here we also noted a drastic reduction of false classifications compared to TMHMM/SignalP, suggesting that Phobius is well suited for whole-genome annotation of signal peptides and transmembrane regions. The method is available at http://phobius.cgb.ki.se/ as well as at http://phobius.binf.ku.dk/},
	number = {5},
	urldate = {2017-11-06TZ},
	journal = {Journal of Molecular Biology},
	author = {Käll, Lukas and Krogh, Anders and Sonnhammer, Erik L. L},
	month = may,
	year = {2004},
	keywords = {hidden Markov model, machine learning, signal peptide, topology prediction, transmembrane protein},
	pages = {1027--1036}
}

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