Abstract

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.

Highlights

  • The successful completion of many genome sequencing projects has left us with an enormous amount of sequence data

  • After reviewing the basic concept of hidden Markov models (HMMs), we introduce three types of HMM variants, namely, profile-HMMs, pairHMMs, and context-sensitive HMMs, that have been useful in various sequence analysis problems

  • A hidden Markov model (HMM) is a statistical model that can be used to describe the evolution of observable events that depend on internal factors, which are not directly observable

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Summary

INTRODUCTION

The successful completion of many genome sequencing projects has left us with an enormous amount of sequence data. We give a tutorial review of HMMs and their applications in biological sequence analysis. Algorithms for solving these problems are introduced. We show how these models and other types of HMMs can be employed in RNA sequence analysis

HIDDEN MARKOV MODELS
Definition
A Simple HMM for Modeling Eukaryotic Genes
Basic Problems and Algorithms for HMMs
Variants of HMMs
PROFILE HIDDEN MARKOV MODELS
Constructing a Profile-HMM
Applications of Profile-HMMs
PAIR HIDDEN MARKOV MODELS
Pair-HMMs for Modeling Aligned Sequence Pairs
Applications of Pair-HMMs
CONTEXT-SENSITIVE HMMS AND PROFILECSHMMS
Context-Sensitive Hidden Markov Models
Profile Context-Sensitive HMMs
Hidden Markov Models in RNA Sequence Analysis
CONCLUDING REMARKS
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