title: Multiple alignment using hidden Markov models.
abstract: A simulated annealing method is described for training hidden Markov models and producing multiple sequence alignments from initially unaligned protein or DNA sequences. Simulated annealing in turn uses a dynamic programming algorithm for correctly sampling suboptimal multiple alignments according to their probability and a Boltzmann temperature factor. The quality of simulated annealing alignments is evaluated on structural alignments of ten different protein families, and compared to the performance of other HMM training methods and the ClustalW program. Simulated annealing is better able to find near-global optima in the multiple alignment probability landscape than the other tested HMM training methods. Neither ClustalW nor simulated annealing produce consistently better alignments compared to each other. Examination of the specific cases in which ClustalW outperforms simulated annealing, and vice versa, provides insight into the strengths and weaknesses of current hidden Markov model approaches.
authors.affiliation: Dept. of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Eddy
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001483:Base Sequence; D016384:Consensus Sequence; D004247:DNA / Q000737:chemistry*; D004815:Epidermal Growth Factor / Q000737:chemistry; D008390:Markov Chains; D008969:Molecular Sequence Data; D016017:Odds Ratio; D011336:Probability; D011506:Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D011506:Proteins; D004815:Epidermal Growth Factor; D004247:DNA