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68
Hidden Markov models in computational biology: applications to protein modeling
 JOURNAL OF MOLECULAR BIOLOGY
, 1994
"... Hidden.Markov Models (HMMs) are applied t.0 the problems of statistical modeling, database searching and multiple sequence alignment of protein families and protein domains. These methods are demonstrated the on globin family, the protein kinase catalytic domain, and the EFhand calcium binding moti ..."
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Cited by 524 (35 self)
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Hidden.Markov Models (HMMs) are applied t.0 the problems of statistical modeling, database searching and multiple sequence alignment of protein families and protein domains. These methods are demonstrated the on globin family, the protein kinase catalytic domain, and the EFhand calcium binding motif. In each case the parameters of an HMM are estimated from a training set of unaligned sequences. After the HMM is built, it is used to obtain a multiple alignment of all the training sequences. It is also used to search the. SWISSPROT 22 database for other sequences. that are members of the given protein family, or contain the given domain. The Hi " produces multiple alignments of good quality that agree closely with the alignments produced by programs that incorporate threedimensional structural information. When employed in discrimination tests (by examining how closely the sequences in a database fit the globin, kinase and EFhand HMMs), the '\ HMM is able to distinguish members of these families from nonmembers with a high degree of accuracy. Both the HMM and PROFILESEARCH (a technique used to search for relationships between a protein sequence and multiply aligned sequences) perform better in these tests than PROSITE (a dictionary of sites and patterns in proteins). The HMM appecvs to have a slight advantage over PROFILESEARCH in terms of lower rates of false
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...
Algorithms for Sequential Decision Making
, 1996
"... Sequential decision making is a fundamental task faced by any intelligent agent in an extended interaction with its environment; it is the act of answering the question "What should I do now?" In this thesis, I show how to answer this question when "now" is one of a finite set of states, "do" is one ..."
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Cited by 177 (8 self)
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Sequential decision making is a fundamental task faced by any intelligent agent in an extended interaction with its environment; it is the act of answering the question "What should I do now?" In this thesis, I show how to answer this question when "now" is one of a finite set of states, "do" is one of a finite set of actions, "should" is maximize a longrun measure of reward, and "I" is an automated planning or learning system (agent). In particular,
The Power of Amnesia: Learning Probabilistic Automata with Variable Memory Length
 Machine Learning
, 1996
"... . We propose and analyze a distribution learning algorithm for variable memory length Markov processes. These processes can be described by a subclass of probabilistic finite automata which we name Probabilistic Suffix Automata (PSA). Though hardness results are known for learning distributions gene ..."
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Cited by 172 (16 self)
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. We propose and analyze a distribution learning algorithm for variable memory length Markov processes. These processes can be described by a subclass of probabilistic finite automata which we name Probabilistic Suffix Automata (PSA). Though hardness results are known for learning distributions generated by general probabilistic automata, we prove that the algorithm we present can efficiently learn distributions generated by PSAs. In particular, we show that for any target PSA, the KLdivergence between the distribution generated by the target and the distribution generated by the hypothesis the learning algorithm outputs, can be made small with high confidence in polynomial time and sample complexity. The learning algorithm is motivated by applications in humanmachine interaction. Here we present two applications of the algorithm. In the first one we apply the algorithm in order to construct a model of the English language, and use this model to correct corrupted text. In the second ...
On the learnability of discrete distributions
 In The 25th Annual ACM Symposium on Theory of Computing
, 1994
"... We introduce and investigate a new model of learning probability distributions from independent draws. Our model is inspired by the popular Probably Approximately Correct (PAC) model for learning boolean functions from labeled ..."
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Cited by 93 (11 self)
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We introduce and investigate a new model of learning probability distributions from independent draws. Our model is inspired by the popular Probably Approximately Correct (PAC) model for learning boolean functions from labeled
Markovian Models for Sequential Data
, 1996
"... Hidden Markov Models (HMMs) are statistical models of sequential data that have been used successfully in many machine learning applications, especially for speech recognition. Furthermore, in the last few years, many new and promising probabilistic models related to HMMs have been proposed. We firs ..."
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Cited by 85 (2 self)
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Hidden Markov Models (HMMs) are statistical models of sequential data that have been used successfully in many machine learning applications, especially for speech recognition. Furthermore, in the last few years, many new and promising probabilistic models related to HMMs have been proposed. We first summarize the basics of HMMs, and then review several recent related learning algorithms and extensions of HMMs, including in particular hybrids of HMMs with artificial neural networks, InputOutput HMMs (which are conditional HMMs using neural networks to compute probabilities), weighted transducers, variablelength Markov models and Markov switching statespace models. Finally, we discuss some of the challenges of future research in this very active area. 1 Introduction Hidden Markov Models (HMMs) are statistical models of sequential data that have been used successfully in many applications in artificial intelligence, pattern recognition, speech recognition, and modeling of biological ...
Robust Trainability of Single Neurons
, 1995
"... It is well known that (McCullochPitts) neurons are efficiently trainable to learn an unknown halfspace from examples, using linearprogramming methods. We want to analyze how the learning performance degrades when the representational power of the neuron is overstrained, i.e., if more complex conce ..."
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Cited by 84 (0 self)
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It is well known that (McCullochPitts) neurons are efficiently trainable to learn an unknown halfspace from examples, using linearprogramming methods. We want to analyze how the learning performance degrades when the representational power of the neuron is overstrained, i.e., if more complex concepts than just halfspaces are allowed. We show that the problem of learning a probably almost optimal weight vector for a neuron is so difficult that the minimum error cannot even be approximated to within a constant factor in polynomial time (unless RP = NP); we obtain the same hardness result for several variants of this problem. We considerably strengthen these negative results for neurons with binary weights 0 or 1. We also show that neither heuristical learning nor learning by sigmoidal neurons with a constant reject rate is efficiently possible (unless RP = NP).
Designing Statistical Language Learners: Experiments on Noun Compounds
, 1995
"... Statistical language learning research takes the view that many traditional natural language processing tasks can be solved by training probabilistic models of language on a sufficient volume of training data. The design of statistical language learners therefore involves answering two questions: (i ..."
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Cited by 78 (0 self)
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Statistical language learning research takes the view that many traditional natural language processing tasks can be solved by training probabilistic models of language on a sufficient volume of training data. The design of statistical language learners therefore involves answering two questions: (i) Which of the multitude of possible language models will most accurately reflect the properties necessary to a given task? (ii) What will constitute a sufficient volume of training data? Regarding the first question, though a variety of successful models have been discovered, the space of possible designs remains largely unexplored. Regarding the second, exploration of the design space has so far proceeded without an adequate answer. The goal of this thesis is to advance the exploration of the statistical language learning design space. In pursuit of that goal, the thesis makes two main theoretical contributions: it identifies a new class of designs by providing a novel theory of statistical natural language processing, and it presents the foundations for a predictive theory of data requirements to assist in future design explorations. The first of these contributions is called the meaning distributions theory. This theory
On the Learnability and Usage of Acyclic Probabilistic Finite Automata
 JOURNAL OF COMPUTER AND SYSTEM SCIENCES
, 1995
"... We propose and analyze a distribution learning algorithm for a subclass of Acyclic Probabilistic Finite Automata (APFA). This subclass is characterized by a certain distinguishability property of the automata's states. Though hardness results are known for learning distributions generated by general ..."
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Cited by 71 (3 self)
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We propose and analyze a distribution learning algorithm for a subclass of Acyclic Probabilistic Finite Automata (APFA). This subclass is characterized by a certain distinguishability property of the automata's states. Though hardness results are known for learning distributions generated by general APFAs, we prove that our algorithm can efficiently learn distributions generated by the subclass of APFAs we consider. In particular, we show that the KLdivergence between the distribution generated by the target source and the distribution generated by our hypothesis can be made arbitrarily small with high confidence in polynomial time. We present two applications of our algorithm. In the first, we show how to model cursively written letters. The resulting models are part of a complete cursive handwriting recognition system. In the second application we demonstrate how APFAs can be used to build multiplepronunciation models for spoken words. We evaluate the APFA based pronunciation models...
Variations on Probabilistic Suffix Trees: Statistical Modeling and Prediction of Protein Families
, 2001
"... Motivation: We present a method for modeling protein families by means of probabilistic suffix trees (PSTs). The method is based on identifying significant patterns in a set of related protein sequences. The patterns can be of arbitrary length, and the input sequences do not need to be aligned, nor ..."
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Cited by 58 (6 self)
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Motivation: We present a method for modeling protein families by means of probabilistic suffix trees (PSTs). The method is based on identifying significant patterns in a set of related protein sequences. The patterns can be of arbitrary length, and the input sequences do not need to be aligned, nor is delineation of domain boundaries required. The method is automatic, and can be applied, without assuming any preliminary biological information, with surprising success. Basic biological considerations such as amino acid background probabilities, and amino acids substitution probabilities can be incorporated to improve performance. Results: The PST can serve as a predictive tool for protein sequence classification, and for detecting conserved patterns (possibly functionally or structurally important) within protein sequences. The method was tested on the Pfam database of protein families with more than satisfactory performance. Exhaustive evaluations show that the PST model detects much more related sequences than pairwise methods such as GappedBLAST, and is almost as sensitive as a hidden Markov model that is trained from a multiple alignment of the input sequences, while being much faster. Availability: The programs are available upon request from the authors. Contact: jill@cs.huji.ac.il; golan@cs.cornell.edu