Biomedical subjects

Ekaterina Shelest

Publications and source records attributed to Ekaterina Shelest.

3 recordsLinked to original sources

PubMed2005

Evaluating phylogenetic footprinting for human-rodent comparisons.

MOTIVATION: 'Phylogenetic footprinting' is a widely applied approach to identify regulatory regions and potential transcription factor binding sites (TFBSs) using alignments of non-coding orthologous regions from two or more organisms. A systematic evaluation of its validity and usability based on known TFBSs is needed to use phylogenetic footprinting most effectively in the identification of unknown TFBSs. RESULTS: In this paper we use 2678 human, mouse and rat TFBSs from the TRANSFAC database for this evaluation. To ensure the retrieval of correct orthologous sequences, we combine gene annotation and sequence homology searches. Demanding a sequence identity of at least 65% is most effective in discriminating TFBSs from non-functional sequence parts, while different alignment algorithms only have a minor influence on TFBS identification by human-rodent comparisons. With this threshold approximately 72% of the known TFBSs are found conserved, a number which varies significantly between different transcription factors and also depends on the function of the regulated gene. TFBSs for certain transcription factors do not require strict sequence conservation but instead may show a high pattern conservation, limiting somewhat the validity of purely sequence-based phylogenetic footprinting.

Animals↗

PubMed2005

Construction of predictive promoter models on the example of antibacterial response of human epithelial cells.

BACKGROUND: Binding of a bacteria to a eukaryotic cell triggers a complex network of interactions in and between both cells. P. aeruginosa is a pathogen that causes acute and chronic lung infections by interacting with the pulmonary epithelial cells. We use this example for examining the ways of triggering the response of the eukaryotic cell(s), leading us to a better understanding of the details of the inflammatory process in general. RESULTS: Considering a set of genes co-expressed during the antibacterial response of human lung epithelial cells, we constructed a promoter model for the search of additional target genes potentially involved in the same cell response. The model construction is based on the consideration of pair-wise combinations of transcription factor binding sites (TFBS). It has been shown that the antibacterial response of human epithelial cells is triggered by at least two distinct pathways. We therefore supposed that there are two subsets of promoters activated by each of them. Optimally, they should be "complementary" in the sense of appearing in complementary subsets of the (+)-training set. We developed the concept of complementary pairs, i.e., two mutually exclusive pairs of TFBS, each of which should be found in one of the two complementary subsets. CONCLUSIONS: We suggest a simple, but exhaustive method for searching for TFBS pairs which characterize the whole (+)-training set, as well as for complementary pairs. Applying this method, we came up with a promoter model of antibacterial response genes that consists of one TFBS pair which should be found in the whole training set and four complementary pairs. We applied this model to screening of 13,000 upstream regions of human genes and identified 430 new target genes which are potentially involved in antibacterial defense mechanisms.

Algorithms↗

PubMed2002

Prediction of potential C/EBP/NF-kappaB composite elements using matrix-based search methods.

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-kappaB plays a central role, but its effects have to be specified by cooperation with additional factors. NF-B 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 previously existing C/EBP matrices, established a model for C/EBP/ NF-kappaB 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).

Base Sequence↗