Skip Navigation


Bioinformatics Advance Access originally published online on March 13, 2009
Bioinformatics 2009 25(16):2103-2109; doi:10.1093/bioinformatics/btp143
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (Print PDF) Freely available
Right arrowOA All Versions of this Article:
25/16/2103    most recent
btp143v1
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
Google Scholar
Right arrow Articles by Pape, U. J.
Right arrow Articles by Vingron, M.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pape, U. J.
Right arrow Articles by Vingron, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Statistical detection of cooperative transcription factors with similarity adjustment

Utz J. Pape 1,2,*, Holger Klein 1 and Martin Vingron 1

1Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestr. 73 and 2Mathematics and Computer Science, Free University of Berlin, Takustr. 9, 14195 Berlin, Germany

*To whom correspondence should be addressed.


  Abstract

Motivation: Statistical assessment of cis-regulatory modules (CRMs) is a crucial task in computational biology. Usually, one concludes from exceptional co-occurrences of DNA motifs that the corresponding transcription factors (TFs) are cooperative. However, similar DNA motifs tend to co-occur in random sequences due to high probability of overlapping occurrences. Therefore, it is important to consider similarity of DNA motifs in the statistical assessment.

Results: Based on previous work, we propose to adjust the window size for co-occurrence detection. Using the derived approximation, one obtains different window sizes for different sets of DNA motifs depending on their similarities. This ensures that the probability of co-occurrences in random sequences are equal. Applying the approach to selected similar and dissimilar DNA motifs from human TFs shows the necessity of adjustment and confirms the accuracy of the approximation by comparison to simulated data. Furthermore, it becomes clear that approaches ignoring similarities strongly underestimate P-values for cooperativity of TFs with similar DNA motifs. In addition, the approach is extended to deal with overlapping windows. We derive Chen–Stein error bounds for the approximation. Comparing the error bounds for similar and dissimilar DNA motifs shows that the approximation for similar DNA motifs yields large bounds. Hence, one has to be careful using overlapping windows. Based on the error bounds, one can precompute the approximation errors and select an appropriate overlap scheme before running the analysis.

Availability: Software to perform the calculation for pairs of position frequency matrices (PFMs) is available at http://mosta.molgen.mpg.de as well as C++ source code for downloading.

Contact: utz.pape{at}molgen.mpg.de

Associate Editor: Trey Ideker

Received on September 29, 2008; revised on February 9, 2009; accepted on March 10, 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.