Biomedical subjects

E Cheremushkin

Publications and source records attributed to E Cheremushkin.

4 recordsLinked to original sources

PubMed2006

Composite Module Analyst: identification of transcription factor binding site combinations using genetic algorithm.

Composite Module Analyst (CMA) is a novel software tool aiming to identify promoter-enhancer models based on the composition of transcription factor (TF) binding sites and their pairs. CMA is closely interconnected with the TRANSFAC database. In particular, CMA uses the positional weight matrix (PWM) library collected in TRANSFAC and therefore provides the possibility to search for a large variety of different TF binding sites. We model the structure of the long gene regulatory regions by a Boolean function that joins several local modules, each consisting of co-localized TF binding sites. Having as an input a set of co-regulated genes, CMA builds the promoter model and optimizes the parameters of the model automatically by applying a genetic-regression algorithm. We use a multicomponent fitness function of the algorithm which includes several statistical criteria in a weighted linear function. We show examples of successful application of CMA to a microarray data on transcription profiling of TNF-alpha stimulated primary human endothelial cells. The CMA web server is freely accessible at http://www.gene-regulation.com/pub/programs/cma/CMA.html. An advanced version of CMA is also a part of the commercial system ExPlaintrade mark (www.biobase.de) designed for causal analysis of gene expression data.

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PubMed2006

Composite Module Analyst: a fitness-based tool for identification of transcription factor binding site combinations.

MOTIVATION: Functionally related genes involved in the same molecular-genetic, biochemical or physiological process are often regulated coordinately. Such regulation is provided by precisely organized binding of a multiplicity of special proteins [transcription factors (TFs)] to their target sites (cis-elements) in regulatory regions of genes. Cis-element combinations provide a structural basis for the generation of unique patterns of gene expression. RESULTS: Here we present a new approach for defining promoter models based on the composition of TF binding sites and their pairs. We utilize a multicomponent fitness function for selection of the promoter model that fits best to the observed gene expression profile. We demonstrate examples of successful application of the fitness function with the help of a genetic algorithm for the analysis of functionally related or co-expressed genes as well as testing on simulated and permutated data. AVAILABILITY: The CMA program is freely available for non-commercial users. URL http://www.gene-regulation.com/pub/programs.html#CMAnalyst. It is also a part of the commercial system ExPlain (www.biobase.de) designed for causal analysis of gene expression data..

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PubMed2003

MATCH: A tool for searching transcription factor binding sites in DNA sequences.

Match is a weight matrix-based tool for searching putative transcription factor binding sites in DNA sequences. Match is closely interconnected and distributed together with the TRANSFAC database. In particular, Match uses the matrix library collected in TRANSFAC and therefore provides the possibility to search for a great variety of different transcription factor binding sites. Several sets of optimised matrix cut-off values are built in the system to provide a variety of search modes of different stringency. The user may construct and save his/her specific user profiles which are selected subsets of matrices including default or user-defined cut-off values. Furthermore a number of tissue-specific profiles are provided that were compiled by the TRANSFAC team. A public version of the Match tool is available at: http://www.gene-regulation.com/pub/programs.html#match. The same program with a different web interface can be found at http://compel.bionet.nsc.ru/Match/Match.html. An advanced version of the tool called Match Professional is available at http://www.biobase.de.

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PubMed2003

Whole genome human/mouse phylogenetic footprinting of potential transcription regulatory signals.

UNLABELLED: Phylogenetic footprinting is an efficient approach for revealing potential transcription factor binding sites in promoter sequences. The idea is based on an assumption that functional sites in promoters should evolve much slower then other regions that do not bear any conservative function. Therefore, potential transcription factor (TF) binding sites that are found in the evolutionally conservative regions of promoters have more chances to be considered as "real" sites. The most difficult step of the phylogenetic footprinting is alignment of promoter sequences between different organisms (fe. human and mouse). The conventional alignment methods often can not align promoters due to the high level of sequence variability. We have developed a new alignment method that takes into account similarity in distribution of potential binding sites (motif-based alignment). This method has been used effectively for promoter alignment and for revealing new potential binding sites for various transcription factors. We made a systematic phylogenetic footprinting of human/mouse conserved non-coding sequences (CNS). 60 thousand potential binding sites were revealed in human and mouse genomes. We have developed a database of the predicted potential TF binding sites. AVAILABILITY: http://compel.bionet.nsc.ru/FunSite/footprint/; www.gene-regulation.com/.

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