Skip Navigation



Bioinformatics Advance Access published online on March 10, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp135
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow All Versions of this Article:
25/9/1125    most recent
btp135v1
Right arrow Comments: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Comments are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Buslje, C. M.
Right arrow Articles by Nielsen, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buslje, C. M.
Right arrow Articles by Nielsen, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2009). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Correction for phylogeny, small number of observations and data redundancy improves the identification of coevolving amino acid pairs using mutual information.

Cristina Marino Buslje 1,*, Javier Santos 1, Jose Maria Delfino 1 and Morten Nielsen 2,*

1Department of Biological Chemistry and Institute of Biochemistry and Biophysics (IQUIFIB), School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
2Centre for Biological Sequence Analysis, Department of Systems Biology. The Technical University of Denmark, Building 208, DK-2800 Lyngby. Denmark

*To whom correspondence should be addressed., E-mail: cmb{at}qb.ffyb.uba.ar; mniel{at}cbs.dtu.dk


  Abstract

Motivation: Mutual information (MI) theory is often applied to predict positional correlations in a multiple sequence alignment (MSA) to make possible the analysis of those positions structurally or func-tionally important in a given fold or protein family. Accurate identifi-cation of coevolving positions in protein sequences is difficult due to the high background signal imposed by phylogeny and noise. Sev-eral methods have been proposed using MI to identify coevolving amino acids in protein families.

Results: After evaluating two current methods, we demonstrate how the use of sequence-weighting techniques to reduce sequence re-dundancy and low-count corrections to account for small number of observations in limited size sequence families, can significantly im-prove the predictability of MI. The evaluation is made on large sets of both in silico-generated alignments as well as on biological se-quence data. The methods included in the analysis are the APC (average product correction) and RCW (row-column weighting) methods. The best performing method was APC including se-quence-weighting and low-count corrections. The use of sequence permutations to calculate a MI rescaling is shown to significantly improve the prediction accuracy and allows for direct comparison of information values across protein families. Finally, we demonstrate how a lower bound of 400 unique sequences is needed in an MSA in order to achieve meaningful predictive performances. With our contribution, we achieve a noteworthy improvement on the current procedures to determine coevolution and residue contacts, and we believe that this will have potential impacts on the understanding of protein structure, function and folding.

Contact: cmb{at}qb.ffyb.uba.ar; mniel{at}cbs.dtu.dk

Associate Editor: Prof. Dmitrij Frishman

Received on October 14, 2008; revised on March 5, 2009; accepted on March 5, 2009

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.