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Multidimensional mutual information methods for the analysis of covariation in multiple sequence alignments.


ABSTRACT: Several methods are available for the detection of covarying positions from a multiple sequence alignment (MSA). If the MSA contains a large number of sequences, information about the proximities between residues derived from covariation maps can be sufficient to predict a protein fold. However, in many cases the structure is already known, and information on the covarying positions can be valuable to understand the protein mechanism and dynamic properties.In this study we have sought to determine whether a multivariate (multidimensional) extension of traditional mutual information (MI) can be an additional tool to study covariation. The performance of two multidimensional MI (mdMI) methods, designed to remove the effect of ternary/quaternary interdependencies, was tested with a set of 9 MSAs each containing <400 sequences, and was shown to be comparable to that of the newest methods based on maximum entropy/pseudolikelyhood statistical models of protein sequences. However, while all the methods tested detected a similar number of covarying pairs among the residues separated by?

SUBMITTER: Clark GW 

PROVIDER: S-EPMC4046016 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Multidimensional mutual information methods for the analysis of covariation in multiple sequence alignments.

Clark Greg W GW   Ackerman Sharon H SH   Tillier Elisabeth R ER   Gatti Domenico L DL  

BMC bioinformatics 20140522


<h4>Background</h4>Several methods are available for the detection of covarying positions from a multiple sequence alignment (MSA). If the MSA contains a large number of sequences, information about the proximities between residues derived from covariation maps can be sufficient to predict a protein fold. However, in many cases the structure is already known, and information on the covarying positions can be valuable to understand the protein mechanism and dynamic properties.<h4>Results</h4>In t  ...[more]

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