Hidden Markov models for sequence analysis: extension and analysis of the basic method

Hidden Markov models (HMMs) are a highly effective means of modeling a family of unalignedsequences or a common motif within a set of unaligned sequences. The trained HMM can then beused for discrimination or multiple alignment. The basic mathematical description of an HMMand its expectation-maximization training procedure is relatively straight-forward. In this paper,we review the mathematical extensions and heuristics that move the method from the theoreticalto the practical. Then, we experimentally analyze the effectiveness of model regularization,dynamic model modification, and optimization strategies. Finally it is demonstrated on the SH2domain how a domain can be found from unaligned sequences using a special model type. Theexperimental work was completed with the aid of the Sequence Alignment and Modeling softwaresuite.