Predicting the phosphorylation sites using hidden Markov models and machine learning methods

Accurately predicting phosphorylation sites in proteins is an important issue in postgenomics, for which how to efficiently extract the most predictive features from amino acid sequences for modeling is still challenging. Although both the distributed encoding method and the bio-basis function method work well, they still have some limits in use. The distributed encoding method is unable to code the biological content in sequences efficiently, whereas the bio-basis function method is a nonparametric method, which is often computationally expensive. As hidden Markov models (HMMs) can be used to generate one model for one cluster of aligned protein sequences, the aim in this study is to use HMMs to extract features from amino acid sequences, where sequence clusters are determined using available biological knowledge. In this novel method, HMMs are first constructed using functional sequences only. Both functional and nonfunctional training sequences are then inputted into the trained HMMs to generate functional and nonfunctional feature vectors. From this, a machine learning algorithm is used to construct a classifier based on these feature vectors. It is found in this work that (1) this method provides much better prediction accuracy than the use of HMMs only for prediction, and (2) the support vector machines (SVMs) algorithm outperforms decision trees and neural network algorithms when they are constructed on the features extracted using the trained HMMs.