Biomedical subjects

A B Goryachev

Publications and source records attributed to A B Goryachev.

3 recordsLinked to original sources

PubMed2005

Systems analysis of a quorum sensing network: design constraints imposed by the functional requirements, network topology and kinetic constants.

Understanding the relationship between the structural organization of intracellular decision networks and the observable phenotypes they control is one of the exigent problems of modern systems biology. Here we perform a systems analysis of a prototypic quorum sensing network whose operation allows bacterial populations to activate certain patterns of gene expression cooperatively. We apply structural perturbations to the model and analyze the resulting changes in the network behavior with the aim to identify the contribution of individual network elements to the functional fitness of the whole network. Specifically, we demonstrate the importance of the dimerization of the transcription factor and the presence of the auxiliary positive feedback loop on the switch-like behavior of the network and the stability of its "on" and "off" states under the influence of molecular noise.

Bacterial Proteins↗

PubMed2001

Unfolding of microarray data.

The use of DNA microarrays for the analysis of complex biological samples is becoming a mainstream part of biomedical research. One of the most commonly used methods compares the relative abundance of mRNA in two different samples by probing a single DNA microarray simultaneously. The simplicity of this concept sometimes masks the complexity of capturing and processing microarray data. On the basis of the analysis of many of our microarray experiments, we identified the major causes of distortion of the microarray data and the sources of noise. In this study, we provide a systematic statistical approach for extraction of true expression ratios from raw microarray data, which we describe as an unfolding process. The results of this analysis are presented in the form of a model describing the relationship between the measured fluorescent intensities and the concentrations of mRNA transcripts. We developed and tested several algorithms for inference of the model parameters for the microarray data. Special emphasis is given to the statistical robustness of these algorithms, in particular resistance to outliers. We also provide methods for measurement of noise and reproducibility of the microarray experiments.

Computational Biology↗

PubMed2001

Herpes simplex virus triggers and then disarms a host antiviral response.

Virus infection induces an antiviral response that is predominantly associated with the synthesis and secretion of soluble interferon. Here, we report that herpes simplex virus type 1 virions induce an interferon-independent antiviral state in human embryonic lung cells that prevents plaquing of a variety of viruses. Microarray analysis of 19,000 human expressed sequence tags revealed induction of a limited set of host genes, the majority of which are also induced by interferon. Genes implicated in controlling the intracellular spread of virus and eliminating virally infected cells were among those induced. Induction of the cellular response occurred in the absence of de novo cellular protein synthesis and required viral penetration. In addition, this response was only seen when viral gene expression was inhibited, suggesting that a newly synthesized viral protein(s) may function as an inhibitor of this response.

Animals↗