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119
The Infinite Hidden Markov Model
 Machine Learning
, 2002
"... We show that it is possible to extend hidden Markov models to have a countably infinite number of hidden states. By using the theory of Dirichlet processes we can implicitly integrate out the infinitely many transition parameters, leaving only three hyperparameters which can be learned from data. Th ..."
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Cited by 488 (33 self)
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We show that it is possible to extend hidden Markov models to have a countably infinite number of hidden states. By using the theory of Dirichlet processes we can implicitly integrate out the infinitely many transition parameters, leaving only three hyperparameters which can be learned from data. These three hyperparameters define a hierarchical Dirichlet process capable of capturing a rich set of transition dynamics. The three hyperparameters control the time scale of the dynamics, the sparsity of the underlying statetransition matrix, and the expected number of distinct hidden states in a finite sequence. In this framework it is also natural to allow the alphabet of emitted symbols to be infiniteconsider, for example, symbols being possible words appearing in English text.
Exploiting Generative Models in Discriminative Classifiers
 In Advances in Neural Information Processing Systems 11
, 1998
"... Generative probability models such as hidden Markov models provide a principled way of treating missing information and dealing with variable length sequences. On the other hand, discriminative methods such as support vector machines enable us to construct flexible decision boundaries and often resu ..."
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Cited by 398 (10 self)
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Generative probability models such as hidden Markov models provide a principled way of treating missing information and dealing with variable length sequences. On the other hand, discriminative methods such as support vector machines enable us to construct flexible decision boundaries and often result in classification performance superior to that of the model based approaches. An ideal classifier should combine these two complementary approaches. In this paper, we develop a natural way of achieving this combination by deriving kernel functions for use in discriminative methods such as support vector machines from generative probability models. We provide a theoretical justification for this combination as well as demonstrate a substantial improvement in the classification performance in the context of DNA and protein sequence analysis.
Hidden Markov models for detecting remote protein homologies
 Bioinformatics
, 1998
"... A new hidden Markov model method (SAMT98) for nding remote homologs of protein sequences is described and evaluated. The method begins with a single target sequence and iteratively builds a hidden Markov model (hmm) from the sequence and homologs found using the hmm for database search. SAMT98 is ..."
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Cited by 306 (12 self)
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A new hidden Markov model method (SAMT98) for nding remote homologs of protein sequences is described and evaluated. The method begins with a single target sequence and iteratively builds a hidden Markov model (hmm) from the sequence and homologs found using the hmm for database search. SAMT98 is also used to construct model libraries automatically from sequences in structural databases. We evaluate the SAMT98 method with four datasets. Three of the test sets are foldrecognition tests, where the correct answers are determined by structural similarity. The fourth uses a curated database. The method is compared against wublastp and against doubleblast, a twostep method similar to ISS, but using blast instead of fasta. Results SAMT98 had the fewest errors in all tests dramatically so for the foldrecognition tests. At the minimumerror point on the SCOPdomains test, SAMT98 got 880 true positives and 68 false positives, doubleblast got 533 true positives with 71 false positives, and wublastp got 353 true positives with 24 false positives. The method is optimized to recognize superfamilies, and would require parameter adjustment to be used to nd family or fold relationships. One key to the performance of the hmm method is a new scorenormalization technique that compares the score to the score with a reversed model rather than to a uniform null model. Availability A World Wide Web server, as well as information on obtaining the Sequence Alignment and PREPRINT to appear in Bioinformatics, 1999
The Hierarchical Hidden Markov Model: Analysis and Applications
 MACHINE LEARNING
, 1998
"... . We introduce, analyze and demonstrate a recursive hierarchical generalization of the widely used hidden Markov models, which we name Hierarchical Hidden Markov Models (HHMM). Our model is motivated by the complex multiscale structure which appears in many natural sequences, particularly in langua ..."
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Cited by 236 (3 self)
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. We introduce, analyze and demonstrate a recursive hierarchical generalization of the widely used hidden Markov models, which we name Hierarchical Hidden Markov Models (HHMM). Our model is motivated by the complex multiscale structure which appears in many natural sequences, particularly in language, handwriting and speech. We seek a systematic unsupervised approach to the modeling of such structures. By extendingthe standard forwardbackward(BaumWelch) algorithm, we derive an efficient procedure for estimating the model parameters from unlabeled data. We then use the trained model for automatic hierarchical parsing of observation sequences. We describe two applications of our model and its parameter estimation procedure. In the first application we show how to construct hierarchical models of natural English text. In these models different levels of the hierarchy correspond to structures on different length scales in the text. In the second application we demonstrate how HHMMs can b...
A Discriminative Framework for Detecting Remote Protein Homologies
, 1999
"... A new method for detecting remote protein homologies is introduced and shown to perform well in classifying protein domains by SCOP superfamily. The method is a variant of support vector machines using a new kernel function. The kernel function is derived from a generative statistical model for a ..."
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Cited by 193 (4 self)
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A new method for detecting remote protein homologies is introduced and shown to perform well in classifying protein domains by SCOP superfamily. The method is a variant of support vector machines using a new kernel function. The kernel function is derived from a generative statistical model for a protein family, in this case a hidden Markov model. This general approach of combining generative models like HMMs with discriminative methods such as support vector machines may have applications in other areas of biosequence analysis as well.
Hidden Markov models for sequence analysis: extension and analysis of the basic method
, 1996
"... Hidden Markov models (HMMs) are a highly effective means of modeling a family of unaligned sequences or a common motif within a set of unaligned sequences. The trained HMM can then be used for discrimination or multiple alignment. The basic mathematical description of an HMM and its expectationmaxi ..."
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Cited by 164 (20 self)
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Hidden Markov models (HMMs) are a highly effective means of modeling a family of unaligned sequences or a common motif within a set of unaligned sequences. The trained HMM can then be used for discrimination or multiple alignment. The basic mathematical description of an HMM and its expectationmaximization training procedure is relatively straightforward. In this paper, we review the mathematical extensions and heuristics that move the method from the theoretical to the practical. Then, we experimentally analyze the effectiveness of model regularization, dynamic model modification, and optimization strategies. Finally it is demonstrated on the SH2 domain how a domain can be found from unaligned sequences using a special model type. The experimental work was completed with the aid of the Sequence Alignment and Modeling software suite. 1 Introduction Since their introduction to the computational biology community (Haussler et al., 1993; Krogh et al., 1994a), hidden Markov models (HMMs...
Using the Fisher kernel method to detect remote protein homologies
 In Proceedings of the Seventh International Conference on Intelligent Systems for Molecular Biology
, 1999
"... A new method, called the Fisher kernel method, for detecting remote protein homologies is introduced and shown to perform well in classifying protein domains by SCOP superfamily. The method is a variant of support vector machines using a new kernel function. The kernel function is derived from a hid ..."
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Cited by 160 (3 self)
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A new method, called the Fisher kernel method, for detecting remote protein homologies is introduced and shown to perform well in classifying protein domains by SCOP superfamily. The method is a variant of support vector machines using a new kernel function. The kernel function is derived from a hidden Markov model. The general approach of combining generative models like HMMs with discriminative methods such as support vector machines may have applications in other areas of biosequence analysis as well.
Combining pairwise sequence similarity and support vector machines for remote protein homology detection
 Proc. 6th Ann. Int. Conf. Computational Molecular Biology
, 2002
"... One key element in understanding the molecular machinery of the cell is to understand the structure and function of each protein encoded in the genome. A very successful means of inferring the structure or function of a previously unannotated protein is via sequence similarity with one or more prote ..."
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Cited by 144 (18 self)
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One key element in understanding the molecular machinery of the cell is to understand the structure and function of each protein encoded in the genome. A very successful means of inferring the structure or function of a previously unannotated protein is via sequence similarity with one or more proteins whose structure or function is already known. Toward this end, we propose a means of representing proteins using pairwise sequence similarity scores. This representation, combined with a discriminative classi � cation algorithm known as the support vector machine (SVM), provides a powerful means of detecting subtle structural and evolutionary relationships among proteins. The algorithm, called SVMpairwise, when tested on its ability to recognize previously unseen families from the SCOP database, yields signi � cantly better performance than SVMFisher, pro � le HMMs, and PSIBLAST. Key words: pairwise sequence comparison, homology, detection, support vector machines. 1.
Multiple alignment using hidden Markov models
 Proc. Int. Conf. Intell. Syst. Mol. Biol
, 1995
"... eddy~genetics.wustl.edu 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 multipl ..."
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Cited by 142 (0 self)
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eddy~genetics.wustl.edu 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 ClnstalW program. Simulated annealing is better able to find nearglobal 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.
Variational learning for switching statespace models
 Neural Computation
, 1998
"... We introduce a new statistical model for time series which iteratively segments data into regimes with approximately linear dynamics and learns the parameters of each of these linear regimes. This model combines and generalizes two of the most widely used stochastic time series models  hidden Ma ..."
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Cited by 142 (6 self)
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We introduce a new statistical model for time series which iteratively segments data into regimes with approximately linear dynamics and learns the parameters of each of these linear regimes. This model combines and generalizes two of the most widely used stochastic time series models  hidden Markov models and linear dynamical systems  and is closely related to models that are widely used in the control and econometrics literatures. It can also be derived by extending the mixture of experts neural network (Jacobs et al., 1991) to its fully dynamical version, in which both expert and gating networks are recurrent. Inferring the posterior probabilities of the hidden states of this model is computationally intractable, and therefore the exact Expectation Maximization (EM) algorithm cannot be applied. However, we present a variational approximation that maximizes a lower bound on the log likelihood and makes use of both the forwardbackward recursions for hidden Markov models and the Kalman lter recursions for linear dynamical systems. We tested the algorithm both on artificial data sets and on a natural data set of respiration force from a patient with sleep apnea. The results suggest that variational approximations are a viable method for inference and learning in switching statespace models.