Biomedical subjects

O Kel-Margoulis

Publications and source records attributed to O Kel-Margoulis.

3 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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PubMed1999

Recognition of NFATp/AP-1 composite elements within genes induced upon the activation of immune cells.

Composite elements are regulatory modules of promoters or enhancers that consist of binding sites of two different but synergizing transcription factors. A well-studied example is nuclear factors of activated T-cell (NFAT) sites which are composite elements of a NFATp/c and an activating protein 1 (AP-1) binding site. We have developed a computational approach to identify potential NFAT target genes which (a) comprises an improved method to scan for individual NFAT composite elements; (b) considers positional effects relative to transcription start sites; and (c) involves cluster analysis of potential NFAT composite elements. All three steps progressively helpX?ed to discriminate T-cell-specific promoter sequences against other functional regions (coding and intronic sequences) of the same genes, against promoters of muscle-specific genes or against random sequences. Using this approach, we identified potential NFAT composite elements in promoters of cytokine genes and their receptors as well as in promoters of genes for AP-1 family members, Ca2+-binding proteins and some other components of the regulatory network operating in activated T-cells and other immune cells. The method developed can be adapted to characterize and identify other composite elements as well. The program for recognition NFAT composite elements is available through the World Wide Web (http://compel.bionet.nsc.ru/FunSite/CompelScan. html and http://transfac.gbf.de/dbsearch/funsitep/s _comp.html).

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