Use Of Omics Technologies Research Articles

Insulin-producing cells and their regulation in physiology and behavior ofDrosophila1This review is part of a virtual symposium on recent advances in understanding a variety of complex regulatory processes in insect physiology and endocrinology, including development, metabolism, cold hardiness, food intake and digestion, and diuresis, through the use of omics technologies in the postgenomic era.

Insulin-like peptide signaling regulates development, growth, reproduction, metabolism, stress resistance, and life span in a wide spectrum of animals. Not only the peptides, but also their tyrosine kinase receptors and the downstream signaling pathways are conserved over evolution. This review summarizes roles of insulin-like peptides (DILPs) in physiology and behavior of Drosophila melanogaster Meigen, 1830. Seven DILPs (DILP1–7) and one receptor (dInR) have been identified in Drosophila. These DILPs display cell and stage specific expression patterns. In the adult, DILP2, 3, and 5 are expressed in insulin-producing cells (IPCs) among the median neurosecretory cells of the brain, DILP7 in 20 neurons of the abdominal ganglion, and DILP6 in the fat body. The DILPs of the IPCs regulate starvation resistance, responses to oxidative and temperature stress, and carbohydrate and lipid metabolism. Furthermore, the IPCs seem to regulate feeding, locomotor activity, sleep and ethanol sensitivity, but the mechanisms are not elucidated. Insulin also alters the sensitivity in the olfactory system that affects food search behavior, and regulates peptidergic neurons that control aspects of feeding behavior. Finally, the control of insulin production and release by humoral and neuronal factors is discussed. This includes a fat body derived factor and the neurotransmitters GABA, serotonin, octopamine, and two neuropeptides.

Systems Pharmacology: Network Analysis to Identify Multiscale Mechanisms of Drug Action

Systems approaches have long been used in pharmacology to understand drug action at the organ and organismal levels. The application of computational and experimental systems biology approaches to pharmacology allows us to expand the definition of systems pharmacology to include network analyses at multiple scales of biological organization and to explain both therapeutic and adverse effects of drugs. Systems pharmacology analyses rely on experimental "omics" technologies that are capable of measuring changes in large numbers of variables, often at a genome-wide level, to build networks for analyzing drug action. A major use of omics technologies is to relate the genomic status of an individual to the therapeutic efficacy of a drug of interest. Combining pathway and network analyses, pharmacokinetic and pharmacodynamic models, and a knowledge of polymorphisms in the genome will enable the development of predictive models of therapeutic efficacy. Network analyses based on publicly available databases such as the U.S. Food and Drug Administration's Adverse Event Reporting System allow us to develop an initial understanding of the context within which molecular-level drug-target interactions can lead to distal effectors in a process that results in adverse phenotypes at the organ and organismal levels. The current state of systems pharmacology allows us to formulate a set of questions that could drive future research in the field. The long-term goal of such research is to develop polypharmacology for complex diseases and predict therapeutic efficacy and adverse event risk for individuals prior to commencement of therapy.

Systems Biology in a Commercial Quality Study of the JapaneseAngelicaRadix: Toward an Understanding of Traditional Medicinal Plants

The commercial quality of Japanese Angelica radices -- Angelica acutiloba Kitagawa (Yamato-toki) and A. acutiloba Kitagawa var. sugiyama Hikino (Hokkai-toki) -- used in Kampo traditional herbal medicines, was studied by use of omics technologies. Complementary and alternative medical providers have observed in their clinical experience that differences in radix commercial quality reflect the differences in pharmacological responses; however, there has been little scientific examination of this phenomenon. The approach of omics, including metabolomics, transcriptomics, genomics, and informatics revealed a distinction between the radix-quality grades based on their metabolites, gene expression in human subjects, and plant genome sequences. Systems biology, constructing a network of omics data used to analyze this complex system, is expected to be a powerful tool for enhancing the study of radix quality and furthering a comprehensive understanding of all medicinal plants.

Exploring In Vitro/In Vivo Correlation: Lessons Learned from Analyzing Phase I Results of the US EPA's ToxCast Project

The research on alternative toxicological methods provides, among other things, a privileged viewpoint on one of the central issues of modern biomedical research—the relationship between (a) biological phenomena observed at the level of tissues and organisms and (b) their cellular and molecular bases as studied in isolated systems in vitro. The newly released ToxCast Phase 1 results, subject to initial analysis, converge with evidence from other fields (e.g., research on drug design with intensive use of omics technologies, traditional research on alternative tests) in indicating a low degree of the in vitro/in vivo correlation overall. In addition, this and other approaches point to the need for combining biological and chemical information in exploring the in vitro to in vivo connection.

“Omics” Technologies and the Immune System

Recent advances in genomics-based identification of gene families and gene polymorphisms associated with immune system dysfunction have answered basic questions in immunology and have begun to move forward our understanding of immune-related disease processes. In toxicology, “omic” technologies have the potential to replace or supplement current immunotoxicological screening procedures, to provide insight into potential mode or mechanisms of action, and to provide data suitable for risk assessment. The application of omic technologies to the study of the immune system also has great potential to appreciably impact the diagnosis and treatment of immune-related diseases. This review focuses on the use of omic technologies in immunopharmacology and immunotoxicology, specifically considering the potential for these technologies to impact chemical hazard identification, risk characterization and risk assessment, and the development and application of novel therapeutics. The state of the science of omics technologies and the immune system is addressed in terms of a continuum of understanding of how omics technologies can and cannot yet be applied in the various aspects of immunopharmacology and immunotoxicology. Additionally, information gaps are identified that, once addressed, will move each area further down the continuum of understanding.

Joint EFPIA/CHMP SWP workshop: the Emerging Use of Omic Technologies for Regulatory Non-Clinical Safety Testing

A workshop was held on October 26-27, 2004, in Bonn, Germany, to discuss the potential use of omic technologies for regulatory non-clinical safety testing of pharmaceuticals. The meeting was hosted by the European Federation of Pharmaceutical Industries and Associations (EFPIA). The workshop was held in conjunction with the 6th European preclinical assessors meeting, which was organized in Bonn by the German Federal Institute for Drugs and Medical Devices (BfArM) and the Safety Working Party (SWP) of the Committee for Medicinal Products for Human Use (CHMP). Approximately 100 scientists, roughly half from the European pharmaceutical industry and half from European regulatory authorities, attended the workshop. The authors of this report constitute the organizing committee members.