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2014 ; 15
(ä): 157
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Multidimensional mutual information methods for the analysis of covariation in
multiple sequence alignments
#MMPMID24886131
Clark GW
; Ackerman SH
; Tillier ER
; Gatti DL
BMC Bioinformatics
2014[May]; 15
(ä): 157
PMID24886131
show ga
BACKGROUND: 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. RESULTS: 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?8 Å in the reference X-ray
structures, there was on average less than 65% overlap between the top scoring
pairs detected by methods that are based on different principles. CONCLUSIONS:
Given the large variety of structure and evolutionary history of different
proteins it is possible that a single best method to detect covariation in all
proteins does not exist, and that for each protein family the best information
can be derived by merging/comparing results obtained with different methods. This
approach may be particularly valuable in those cases in which the size of the MSA
is small or the quality of the alignment is low, leading to significant
differences in the pairs detected by different methods.