Prediction of signal peptides and signal anchors by a hidden Markov model

A hidden Markov model of signal peptides has been devel-oped. It contains submodels for the N-terminal part, the hy-drophobic region, and the region around the cleavage site. For known signal peptides, the model can be used to assign objec-tive boundaries between these three regions. Applied to our data, the length distributions for the three regions are signifi-cantly different from expectations. For instance, the assigned hydrophobic region is between 8 and 12 residues long in al-most all eukaryotic signal peptides. This analysis also makes obvious the difference between eukaryotes, Gram-positive bacteria, and Gram-negative bacteria. The model can be used to predict the location of the cleavage site, which it finds cor-rectly in nearly 70 % of signal peptides in a cross-validated test—almost the same accuracy as the best previous method. One of the problems for existing prediction methods is the poor discrimination between signal peptides and uncleaved signal anchors, but this is substantially improved by the hid-den Markov model when expanding it with a very simple sig-nal anchor model