In Silico Biology - Volume 3, issue 1-2

Authors: Kolchanov, Nikolay | Hofestädt, Ralf

Article Type: Other

Citation: In Silico Biology, vol. 3, no. 1-2, pp. 1-2, 2003

Authors: Kazakov, Alexei E. | Vassieva, Olga | Gelfand, Mikhail S. | Osterman, Andrei | Overbeek, Ross

Article Type: Research Article

Abstract: PhoH protein is a putative ATPase belonging to the phosphate regulon in Escherichia coli. EC-PhoH homologs are present in different organisms, but it is not clear if they are functionally related, besides nothing is known about their regulation. To distinguish true functional orthologs of EC-PhoH in different classes of bacteria and to identify their functional role in bacterial metabolic network we performed phylogenetic analysis of these proteins and comparative study of position and regulation of the …related genes. Three groups of proteins were identified. Proteins of the first group (BS-PhoH orthologs) are present in most of bacteria and are proposed to be functionally linked to phospholipid metabolism and RNA modification. Proteins of the second group (BS-YlaK orthologs) are present in most of aerobes, and Actinobacterial YlaK orthologs are shown to be members of a fatty acid beta-oxidation regulons. EC-PhoH orthologs are classified in a third group, specific for Enterobacteria. Functional role of PhoH homologs in the lipid and RNA metabolism and proposed interrelation of PhoH paralogs in one organism are discussed. Show more

Keywords: PhoH, regulon, Mycobacterium, phylogenetic analysis, gene clusters, phospholipid

Citation: In Silico Biology, vol. 3, no. 1-2, pp. 3-15, 2003

Authors: Lyubetsky, Vassily A. | V'yugin, Vladimir V.

Article Type: Research Article

Abstract: A new approach for comparative analysis of multiple trees reconstructed for representative protein families is proposed. This approach is based on the hypothesis of gene duplication, gene loss and horizontal gene transfer and makes use of stochastic methods and optimization. We present a species tree of 40 prokaryotic organisms obtained by our algorithm on the basis of 132 clusters of orthologous groups of proteins (COGs) from the GenBank of the National Center for Biotechnology Information (USA). …We also present a computer technology intended to determine horizontally transferred genes. Some application results of the technology, based on comparative analysis of protein and species trees, are given. Show more

Keywords: evolution, phylogenetic trees, consensus trees, horizontal gene transfer, mathematical models of evolution, stochastic optimization

Citation: In Silico Biology, vol. 3, no. 1-2, pp. 17-31, 2003

Authors: Danilova, Ludmila V. | Lyubetsky, Vassily A. | Gelfand, Mikhail S.

Article Type: Research Article

Abstract: We describe an algorithm (IRSA) for identification of common regulatory signals in samples of unaligned DNA sequences. The algorithm was tested on randomly generated sequences of fixed length with implanted signal of length 15 with 4 mutations, and on natural upstream regions of bacterial genes regulated by PurR, ArgR and CRP. Then it was applied to upstream regions of orthologous genes from Escherichia coli and related genomes. Some new palindromic binding and direct repeats signals were …identified. Finally we present a parallel version suitable for computers supporting the MPI protocol. This implementation is not strictly bounded by the number of available processors. The computation speed linearly depends on the number of processors. Show more

Keywords: bioinformatics, regulatory signals, bacterial genomes, orthologous genes, parallel computing, MPI protocol

Citation: In Silico Biology, vol. 3, no. 1-2, pp. 33-47, 2003

Authors: Stavrovskaya, Elena D. | Mironov, Andrey A.

Article Type: Research Article

Abstract: There exist numerous algorithms for identification of regulatory signals in unaligned DNA fragments. Here we present two genetic algorithms for signal identification and describe their implementation and testing on simulated and real data. The first algorithm selects the start position of the signal in a given fragment. The second one builds a "universal" word that is recognized by the transcription factor. We compare these approaches and study the behavior of the genetic algorithm.

Keywords: regulation signal, genetic algorithms

Citation: In Silico Biology, vol. 3, no. 1-2, pp. 49-56, 2003

Authors: Lockwood, Christopher R. | Frayling, Timothy M.

Article Type: Research Article

Abstract: The identification of regulatory elements in silico is an important method for inferring function from sequence data, but it is uncertain which methods are best. We used a novel combination of expression data from a TCF1 knockout mouse (TCF1 codes for the transcription factor HNF1α), and human and mouse genome sequences, to search 2kb upstream of 28 genes downregulated in TCF1 null mice compared to wild type mice. We wrote software (http://www.BindGene.org) to search for and …assign p-values to potential binding sites. This identified 8 genes as candidates for being directly regulated by HNF1α: LIPC, CRP, F13B, PRODH2, HSD17B2, SCL7A9, SLC16A7, PAH. There was evidence for conservation between human and mouse for all these regions identified as containing putative binding sites. For three of the genes identified there was experimental evidence for an HNF1α binding site. For comparison we also examined 25 genes up-regulated in TCF1 null mice; only one gene was selected and there was little evidence for conservation of this putative binding site between human and mouse. This result was consistent with HNF1α being a gene transcription activator. Another 6 up-regulated genes had unexpectedly high p-values, suggesting that possibly HNF1α sites have been suppressed from these genes. In conclusion, gene expression data from transgenic animals lacking a transcription factor can be used to identify DNA binding sites for that factor. Show more

Keywords: HNF1, transcription factor, binding site, knockout mouse, expression data, positional weight matrix, PWM

Citation: In Silico Biology, vol. 3, no. 1-2, pp. 57-70, 2003

Authors: Shelest, Ekaterina | Kel, Alexander | Gößling, Ellen | Wingender, Edgar

Article Type: Research Article

Abstract: Bacterial infections trigger a wide range of host cell responses. For the interaction of Pseudomonas aeruginosa and epithelial cells it is known that transcription factor NF-κB plays a central role, but its effects have to be specified by cooperation with additional factors. NF-κB containing composite elements, e.g. with C/EBP, may be appropriate indicators for new antibacterial response genes. We refined matrix-based search methods for C/EBP, which was necessary because of weak consensi …of the previosly existing C/EBP matrices, established a model for C/EBP / NF-κB composite element, used it for scanning all known human 5'-flanking sequences and identified 135 new candidate genes. The newly constructed C/EBP binding patterns will be available with one of the next releases of the TRANSFAC database (http://www.gene-regulation.de). Show more

Keywords: promoters, regulatory sequence signals, transcription factors, transcription factor binding sites, composite elements, antibacterial response

Citation: In Silico Biology, vol. 3, no. 1-2, pp. 71-79, 2003

Authors: Levitsky, Victor G. | Katokhin, Alexey V.

Article Type: Research Article

Abstract: A new approach to recognizing promoter regions of eukaryotic genes is proposed and illustrated by an example of Drosophila melanogaster. The essence of its novelty is in realizing the genetic algorithm to search for optimal partition of a promoter region into local nonoverlapping fragments and selection of the most significant dinucleotide frequencies for the fragments obtained. The method developed was applied to recognizing TATA-containing (TATA+) and DPE-containing (DPE+) promoters of Drosophila melanogaster genes. …The program for promoter recognition is included into the GeneExpress system, section RegScan (http://wwwmgs.bionet.nsc.ru/mgs/programs/proga/). Show more

Keywords: eukaryotic promoter recognition, genetic algorithml, discriminant analysis, promoter region partition, dinucleotide frequencies, TATA-containing promoters, DPE-containing promoters, nucleosome formation potentia

Citation: In Silico Biology, vol. 3, no. 1-2, pp. 81-87, 2003

Authors: Spirov, Alexander V. | Holloway, David M.

Article Type: Research Article

Abstract: We quantify fluctuations in protein expression for three of the segmentation genes in the fruit fly, Drosophila melanogaster. These proteins are representative members of the first three levels of a signalling hierarchy which determines the segmented body plan: maternal (Bicoid protein); gap (Hunchback protein); and pair-rule (Even-skipped protein). We quantify both inter-embryo and inter-nucleus (within a single embryo) variability in expression, especially with respect to positional specification by concentration gradient reading. Errors …are quantified both early and late in cleavage cycle 14, during which the protein patterns develop, to study the dynamics of error transmission. We find that Bicoid displays very large positional errors, while expression of the downstream genes, Hunchback and Even-skipped, displays far more precise positioning. This is evidence that the pattern formation of the downstream proteins is at least partially independent of maternal signal, i.e. evidence against simple concentration gradient reading. We also find that fractional errors in concentration increase during cleavage cycle 14. Show more

Keywords: morphogens, pattern formation, gradient reading, genetic cascades, positional information, gene networks, signalling hierarchy, concentration noise, embryo segmentation, maternal genes, gap genes, pair-rule genes, embryo-to-embryo variability, nucleus-to-nucleus variability, genetic algorithms, stochastic, error transmission, axis specification, image processing, Drosophila melanogaster

Citation: In Silico Biology, vol. 3, no. 1-2, pp. 89-100, 2003

Authors: Tchuraev, Rustem N. | Galimzyanov, Alexander V.

Article Type: Research Article

Abstract: Using the method of generalized threshold models, the problem is formulated and solved to evaluate the parametric stability of the model of a gene subnetwork controlling the early ontogenesis of the fruit fly Droso-phila melanogaster. Computer experiments have been performed to test the parametric stability of the model. Quan-titative evaluations have been obtained for parametric stability of the Drosophila gene subnetwork in nuclei along the embryo's anterior-posterior axis. The results of computer experiments have been …compared with the previous research data on "sensitivity" of functioning regimes to random changes of the parameters in the models of prokary-otic and eukaryotic systems, namely the system controlling the λ-phage development and the subsystem controlling the flower morphogenesis of Arabidopsis thaliana. The obtained results confirm high parametric stability of gene networks that control the development of organisms. Show more

Keywords: Control gene networks, Drosophila melanogaster, generalised threshold models, computer experiments, parametric stability

Citation: In Silico Biology, vol. 3, no. 1-2, pp. 101-115, 2003