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An integrative computational approach to effectively guide experimental identification of regulatory elements in promoters

Authors: Deyneko, Igor V; Weiss, Siegfried; Leschner, Sara;

An integrative computational approach to effectively guide experimental identification of regulatory elements in promoters

Abstract

Transcriptional activity of genes depends on many factors like DNA motifs, conformational characteristics of DNA, melting etc. and there are computational approaches for their identification. However, in real applications, the number of predicted, for example, DNA motifs may be considerably large. In cases when various computational programs are applied, systematic experimental knock out of each of the potential elements obviously becomes nonproductive. Hence, one needs an approach that is able to integrate many heterogeneous computational methods and upon that suggest selected regulatory elements for experimental verification.Here, we present an integrative bioinformatic approach aimed at the discovery of regulatory modules that can be effectively verified experimentally. It is based on combinatorial analysis of known and novel binding motifs, as well as of any other known features of promoters. The goal of this method is the identification of a collection of modules that are specific for an established dataset and at the same time are optimal for experimental verification. The method is particularly effective on small datasets, where most statistical approaches fail. We apply it to promoters that drive tumor-specific gene expression in tumor-colonizing Gram-negative bacteria. The method successfully identified a number of potential modules, which required only a few experiments to be verified. The resulting minimal functional bacterial promoter exhibited high specificity of expression in cancerous tissue.Experimental analysis of promoter structures guided by bioinformatics has proved to be efficient. The developed computational method is able to include heterogeneous features of promoters and suggest combinatorial modules for experimental testing. Expansibility and robustness of the methodology implemented in the approach ensures good results for a wide range of problems.

Country
Germany
Keywords

QH301-705.5, Methodology Article, Computer applications to medicine. Medical informatics, R858-859.7, Computational Biology, Gene Expression, Sequence Analysis, DNA, DNA motifs, Biochemistry, Cis-regulatory modules, Computer Science Applications, Transcriptional regulation, Salmonella, Neoplasms, Biology (General), Nucleotide Motifs, Promoter Regions, Genetic, Molecular Biology, Algorithms

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    7
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
7
Average
Average
Average
Green
gold
Related to Research communities
Cancer Research