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Recovering motifs from biased genomes: application of signal correction.

Hasan S, Schreiber M - Nucleic Acids Res. (2006)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Novartis Institute for Tropical Diseases (NITD), 10 Biopolis Road, #05-01 Chromos, Singapore 138670.

ABSTRACT
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.

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Related in: MedlinePlus

Eigenvectors of the two major principal components of (a) raw and (b) corrected RBS signals. The co-ordinates on the x-axis correspond to the co-ordinates of the example motif in Figure 2.
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fig7: Eigenvectors of the two major principal components of (a) raw and (b) corrected RBS signals. The co-ordinates on the x-axis correspond to the co-ordinates of the example motif in Figure 2.

Mentions: Performing PCA on the raw signals showed only a weak tendency for the results to be sorted by %GC on the PCA1 axis (linear R2 = 0.53) and this accounted for 51% of the variation (Figure 6a). Comparison of the eigenvectors of these two principal components showed that PCA1 was accounted for by variation in both non-coding and triplet bias whereas PCA2 was accounted for by variation in the SD motif (Figure 7a).


Recovering motifs from biased genomes: application of signal correction.

Hasan S, Schreiber M - Nucleic Acids Res. (2006)

Eigenvectors of the two major principal components of (a) raw and (b) corrected RBS signals. The co-ordinates on the x-axis correspond to the co-ordinates of the example motif in Figure 2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1636444&req=5

fig7: Eigenvectors of the two major principal components of (a) raw and (b) corrected RBS signals. The co-ordinates on the x-axis correspond to the co-ordinates of the example motif in Figure 2.
Mentions: Performing PCA on the raw signals showed only a weak tendency for the results to be sorted by %GC on the PCA1 axis (linear R2 = 0.53) and this accounted for 51% of the variation (Figure 6a). Comparison of the eigenvectors of these two principal components showed that PCA1 was accounted for by variation in both non-coding and triplet bias whereas PCA2 was accounted for by variation in the SD motif (Figure 7a).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Novartis Institute for Tropical Diseases (NITD), 10 Biopolis Road, #05-01 Chromos, Singapore 138670.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus