Hidden Markov Models and their Applications in Biological Sequence Analysis

Hidden Markov models (HMMs) have been extensively used in biological sequence analysis. In this paper, we give a tutorial review of HMMs and their applications in a variety of problems in molecular biology. We especially focus on three types of HMMs: the profile-HMMs, pair-HMMs, and context-sensitive HMMs. We show how these HMMs can be used to solve various sequence analysis problems, such as pairwise and multiple sequence alignments, gene annotation, classification, similarity search, and many others.

• Publication year

  2009

• Venue

  Current Genomics

• Publication date

  2009-08-31

• Fields of study

  Biology, Medicine, Computer Science

• Identifiers
  DOI 10.2174/138920209789177575PMID 20190955PMCID 2766791
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Viterbi Algorithm

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• Computational identification and analysis of noncoding RNAs - Unearthing the buried treasures in the genorne

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• Efficient pairwise RNA structure prediction using probabilistic alignment constraints in Dynalign

  2007influential reference
• HMM-ModE – Improved classification using profile hidden Markov models by optimising the discrimination threshold and modifying emission probabilities with negative training sequences

  2007cited by this paper
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  2006influential reference
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  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
• BMC Bioinformatics BioMed Central Methodology article Efficient pairwise RNA structure prediction and alignment using sequence alignment constraints

  2006cited by this paper
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• ProbCons: Probabilistic consistency-based multiple sequence alignment.

  2005influential reference
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  2005cited by this paper
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  2005cited by this paper
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  2003influential reference
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  2001influential reference
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  2000cited by this paper
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  1999cited by this paper
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  1998cited by this paper
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  1998cited by this paper
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  1997cited by this paper
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  1997cited by this paper
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  1997cited by this paper
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  1995cited by this paper
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  1994cited by this paper
• Stochastic context-free grammars for tRNA modeling.

  1994cited by this paper
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  1993cited by this paper
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