Biomedical subjects

Ivan Ovcharenko

Publications and source records attributed to Ivan Ovcharenko.

21 records · Page 2Linked to original sources

PubMed2003

Phylogenetic shadowing of primate sequences to find functional regions of the human genome.

Nonhuman primates represent the most relevant model organisms to understand the biology of Homo sapiens. The recent divergence and associated overall sequence conservation between individual members of this taxon have nonetheless largely precluded the use of primates in comparative sequence studies. We used sequence comparisons of an extensive set of Old World and New World monkeys and hominoids to identify functional regions in the human genome. Analysis of these data enabled the discovery of primate-specific gene regulatory elements and the demarcation of the exons of multiple genes. Much of the information content of the comprehensive primate sequence comparisons could be captured with a small subset of phylogenetically close primates. These results demonstrate the utility of intraprimate sequence comparisons to discover common mammalian as well as primate-specific functional elements in the human genome, which are unattainable through the evaluation of more evolutionarily distant species.

Animals↗

PubMed2003

CREME: a framework for identifying cis-regulatory modules in human-mouse conserved segments.

MOTIVATION: The binding of transcription factors to specific regulatory sequence elements is a primary mechanism for controlling gene transcription. Recent findings suggest a modular organization of binding sites for transcription factors that cooperate in the regulation of genes. In this work we establish a framework for finding recurrent cis-regulatory modules in the promoters of a selected set of genes and scoring their statistical significance. RESULTS: Proceeding from a database of identified binding site motifs and their genomic locations we seek motifs whose frequency in the selected promoters is different than in a background promoter set. We present several statistical tests designed for this purpose. We provide a hashing algorithm for detecting combinations of these motifs that co-occur in clusters within the selected promoters. The significance of such co-occurrences is evaluated using novel statistical scores. Our methods are combined in CREME, a suite of software which includes a browser for viewing the pattern of occurrence of selected cis-regulatory modules. We applied our methodology to find modules within human-mouse conserved promoter segments, focusing on cell cycle regulated genes and stress response related genes. To validate the biological significance of the identified modules we tested whether the associated genes tended to be co-expressed or share similar function. In the cell cycle set five of the seven identified sets of genes were coherently expressed. On the stress response data four of the six detected sets fell predominantly into well-defined functional sub-categories.

Algorithms↗

PubMed2002

rVista for comparative sequence-based discovery of functional transcription factor binding sites.

Identifying transcriptional regulatory elements represents a significant challenge in annotating the genomes of higher vertebrates. We have developed a computational tool, rVista, for high-throughput discovery of cis-regulatory elements that combines clustering of predicted transcription factor binding sites (TFBSs) and the analysis of interspecies sequence conservation to maximize the identification of functional sites. To assess the ability of rVista to discover true positive TFBSs while minimizing the prediction of false positives, we analyzed the distribution of several TFBSs across 1 Mb of the well-annotated cytokine gene cluster (Hs5q31; Mm11). Because a large number of AP-1, NFAT, and GATA-3 sites have been experimentally identified in this interval, we focused our analysis on the distribution of all binding sites specific for these transcription factors. The exploitation of the orthologous human-mouse dataset resulted in the elimination of > 95% of the approximately 58,000 binding sites predicted on analysis of the human sequence alone, whereas it identified 88% of the experimentally verified binding sites in this region.

Animals↗