Hidden Markov Models (HMMs) are probabilistic models widely used in computational molecular biology. However, the Markovian assumption regarding transition probabilities which dictates that the observed symbol depends only on the current state may not be sufficient for some biological problems. In order to overcome the limitations of the first order HMM, a number of extensions have been proposed in the literature to incorporate past information in HMMs conditioning either on the hidden states, or on the observations, or both. Here, we implement a simple extension of the standard HMM in which the current observed symbol (amino acid residue) depends both on the current state and on a series of observed previous symbols. The major advantage of the method is the simplicity in the implementation, which is achieved by properly transforming the observation sequence, using an extended alphabet. Thus, it can utilize all the available algorithms for the training and decoding of HMMs. We investigated the use of several encoding schemes and performed tests in a number of important biological problems previously studied by our team (prediction of transmembrane proteins and prediction of signal peptides). The evaluation shows that, when enough data are available, the performance increased by 1.8%-8.2% and the existing prediction methods may improve using this approach. The methods, for which the improvement was significant (PRED-TMBB2, PRED-TAT and HMM-TM), are available as web-servers freely accessible to academic users at www.compgen.org/tools/ .
Keywords: Hidden Markov models; biological sequence analysis; prediction methods.