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In recent years, the maturation of microarray technology has allowed the genome-wide analysis of gene expression patterns to identify tissue-specific and ubiquitously expressed ('housekeeping') genes. We have performed a functional and topological analysis of housekeeping and tissue-specific networks to identify universally necessary biological processes,(More)
The challenge of predicting the metabolism or toxicity of a drug in humans has been approached using in vivo animal models, in vitro systems, high throughput genomics and proteomics methods, and, more recently, computational approaches. Understanding the complexity of biological systems requires a broader perspective rather than focusing on just one method(More)
There is an urgent requirement within the pharmaceutical and biotechnology industries, regulatory authorities and academia to improve the success of molecules that are selected for clinical trials. Although absorption, distribution, metabolism, excretion and toxicity (ADME/Tox) properties are some of the many components that contribute to successful drug(More)
Traditionally, gene signatures are statistically deduced from large gene expression and proteomics datasets and have been applied as an experimental molecular diagnostic technique that is sensitive to experimental design and statistical treatment. We have developed and applied the approach of "signature networks" which overcomes some of the drawbacks of(More)
Depletion of endoplasmic reticulum Ca2+ stores leads to the entry of extracellular Ca2+ into the cytoplasm, a process termed capacitative or store-operated Ca2+ entry. Partially purified extracts were prepared from the human Jurkat T lymphocyte cell line and yeast in which Ca2+ stores were depleted by chemical and genetic means, respectively. After(More)
Cellular life can be represented and studied as the 'interactome'--a dynamic network of biochemical reactions and signaling interactions between active proteins. Systemic networks analysis can be used for the integration and functional interpretation of high-throughput experimental data, which are abundant in drug discovery but currently poorly utilized.(More)
We study the propagation of intracellular calcium waves in a model that features Ca2+ release from discrete sites in the endoplasmic reticulum membrane and random spatial distribution of these sites. The results of our simulations qualitatively reproduce the experimentally observed behavior of the waves. When the level of the channel activator inositol(More)
The complexity of human biology requires a systems approach that uses computational approaches to integrate different data types. Systems biology encompasses the complete biological system of metabolic and signaling pathways, which can be assessed by measuring global gene expression, protein content, metabolic profiles, and individual genetic, clinical, and(More)
Many of the drug candidates that fail in clinical trials are withdrawn because of unforeseen effects of human metabolism, such as toxicity and unfavorable pharmacokinetic profiles. Early pre-clinical elimination of such compounds is important but not yet possible. An ideal system would enable researchers to make a confident elimination decision based purely(More)
Exposure to arsenic causes cancer by inducing a variety of responses that affect the expression of genes associated with numerous biological pathways leading to altered cell growth and proliferation, signaling, apoptosis and oxidative stress response. Affymetrix GeneChip arrays were used to detect gene expression changes following dimethylarsinic acid (DMA)(More)