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

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A comprehensive assessment of N-terminal signal peptides prediction methods

Khar Heng Choo12*, Tin Wee Tan2 and Shoba Ranganathan23*

Author Affiliations

1 Institute for Infocomm Research, 1 Fusionopolis Way, #21-01 Connexis, Singapore 138632

2 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597

3 Department of Chemistry and Biomolecular Sciences & ARC Centre of Excellence in Bioinformatics, Macquarie University, Sydney NSW 2109, Australia

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BMC Bioinformatics 2009, 10(Suppl 15):S2  doi:10.1186/1471-2105-10-S15-S2

Published: 3 December 2009



Amino-terminal signal peptides (SPs) are short regions that guide the targeting of secretory proteins to the correct subcellular compartments in the cell. They are cleaved off upon the passenger protein reaching its destination. The explosive growth in sequencing technologies has led to the deposition of vast numbers of protein sequences necessitating rapid functional annotation techniques, with subcellular localization being a key feature. Of the myriad software prediction tools developed to automate the task of assigning the SP cleavage site of these new sequences, we review here, the performance and reliability of commonly used SP prediction tools.


The available signal peptide data has been manually curated and organized into three datasets representing eukaryotes, Gram-positive and Gram-negative bacteria. These datasets are used to evaluate thirteen prediction tools that are publicly available. SignalP (both the HMM and ANN versions) maintains consistency and achieves the best overall accuracy in all three benchmarking experiments, ranging from 0.872 to 0.914 although other prediction tools are narrowing the performance gap.


The majority of the tools evaluated in this study encounter no difficulty in discriminating between secretory and non-secretory proteins. The challenge clearly remains with pinpointing the correct SP cleavage site. The composite scoring schemes employed by SignalP may help to explain its accuracy. Prediction task is divided into a number of separate steps, thus allowing each score to tackle a particular aspect of the prediction.