Nucleic Acids Research Advance Access originally published online on September 20, 2006
Nucleic Acids Research 2006 34(18):5124-5132; doi:10.1093/nar/gkl676
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Nucleic Acids Research, 2006, Vol. 34, No. 18 5124-5132
© 2006 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.
Computational Biology |
Recovering motifs from biased genomes: application of signal correction
Novartis Institute for Tropical Diseases (NITD) 10 Biopolis Road, #05-01 Chromos, Singapore 138670
*To whom correspondence should be addressed. Tel: +65 6722 2900; Fax: +65 6722 2910; Email: mark.schreiber{at}novartis.com
Received July 27, 2006. Revised August 30, 2006. Accepted August 30, 2006.
A significant problem in biological motif analysis arises when the background symbol distribution is biased (e.g. high/low GC content in the case of DNA sequences). This can lead to overestimation of the amount of information encoded in a motif. A motif can be depicted as a signal using information theory (IT). We apply two concepts from IT, distortion and patterned interference (a type of noise), to model genomic and codon bias respectively. This modeling approach allows us to correct a raw signal to recover signals that are weakened by compositional bias. The corrected signal is more likely to be discriminated from a biased background by a macromolecule. We apply this correction technique to recover ribosome-binding site (RBS) signals from available sequenced and annotated prokaryotic genomes having diverse compositional biases. We observed that linear correction was sufficient for recovering signals even at the extremes of these biases. Further comparative genomics studies were made possible upon correction of these signals. We find that the average Euclidian distance between RBS signal frequency matrices of different genomes can be significantly reduced by using the correction technique. Within this reduced average distance, we can find examples of class-specific RBS signals. Our results have implications for motif-based prediction, particularly with regards to the estimation of reliable inter-genomic model parameters.