Publications (5)30.41 Total impact
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Article: Current and future applications of toxicogenomics: Results summary of a survey from the HESI Genomics State of Science Subcommittee.
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ABSTRACT: In spite of the application of toxicogenomic (TGx) data to the field of toxicology for the past 10 years, the broad implementation and full impact of TGx for chemical and drug evaluation to improve decision making within organizations and by policy makers has not been achieved. The goal of the Health and Environmental Sciences Institute (HESI) Committee on the Application of Genomics to Mechanism-based Risk Assessment was to construct and summarize a multisector survey, addressing key issues and perspectives on the current and future practical uses and challenges of implementing TGx data to facilitate discussions for decision making within organizations and by policy makers. An online survey to probe the current status and future challenges facing the field of TGx for drug and chemical evaluation in experimental and nonclinical models was taken by scientists and scientific decision/policy makers actively engaged in the field of TGx within industrial, academic, and regulatory sectors of the United States, Europe, and Japan. For this survey, TGx refers specifically to the analysis of gene expression responses to evaluate xenobiotic exposure in experimental and preclinical models. The survey results are summarized from questions covering broad areas including technology used, organizational capacity and resource allocation, experimental approaches, data storage and exchange, perceptions of benefits and hurdles, and future expectations. The survey findings provide valuable information on the current state of the science of TGx applications and identify key areas in which TGx will have an impact as well as the key hurdles in applying TGx data to address issues. The findings serve as a public resource to facilitate discussions on the focus of future TGx efforts to ensure that a maximal benefit can be obtained from toxicogenomic studies.Environmental Health Perspectives 07/2010; 118(7):992-7. · 7.04 Impact Factor -
Article: Toward a checklist for exchange and interpretation of data from a toxicology study.
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ABSTRACT: Data from toxicology and toxicogenomics studies are valuable, and can be combined for meta-analysis using public data repositories such as Chemical Effects in Biological Systems Knowledgebase, ArrayExpress, and Gene Expression Omnibus. In order to fully utilize the data for secondary analysis, it is necessary to have a description of the study and good annotation of the accompanying data. This study annotation permits sophisticated cross-study comparison and analysis, and allows data from comparable subjects to be identified and fully understood. The Minimal Information About a Microarray Experiment Standard was proposed to permit deposition and sharing of microarray data. We propose the first step toward an analogous standard for a toxicogenomics/toxicology study, by describing a checklist of information that best practices would suggest be included with the study data. When the information in this checklist is deposited together with the study data, the checklist information helps the public explore the study data in context of time, or identify data from similarly treated subjects, and also explore/identify potential sources of experimental variability. The proposed checklist summarizes useful information to include when sharing study data for publication, deposition into a database, or electronic exchange with collaborators. It is not a description of how to carry out an experiment, but a definition of how to describe an experiment. It is anticipated that once a toxicology checklist is accepted and put into use, then toxicology databases can be configured to require and output these fields, making it straightforward to annotate data for interpretation by others.Toxicological Sciences 10/2007; 99(1):26-34. · 4.65 Impact Factor -
Article: Chemical effects in biological systems--data dictionary (CEBS-DD): a compendium of terms for the capture and integration of biological study design description, conventional phenotypes, and 'omics data.
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ABSTRACT: A critical component in the design of the Chemical Effects in Biological Systems (CEBS) Knowledgebase is a strategy to capture toxicogenomics study protocols and the toxicity endpoint data (clinical pathology and histopathology). A Study is generally an experiment carried out during a period of time for the purpose of obtaining data, and the Study Design Description captures the methods, timing, and organization of the Study. The CEBS Data Dictionary (CEBS-DD) has been designed to define and organize terms in an attempt to standardize nomenclature needed to describe a toxicogenomics Study in a structured yet intuitive format and provide a flexible means to describe a Study as conceptualized by the investigator. The CEBS-DD will organize and annotate information from a variety of sources, thereby facilitating the capture and display of toxicogenomics data in biological context in CEBS, i.e., associating molecular events detected in highly-parallel data with the toxicology/pathology phenotype as observed in the individual Study Subjects and linked to the experimental treatments. The CEBS-DD has been developed with a focus on acute toxicity studies, but with a design that will permit it to be extended to other areas of toxicology and biology with the addition of domain-specific terms. To illustrate the utility of the CEBS-DD, we present an example of integrating data from two proteomics and transcriptomics studies of the response to acute acetaminophen toxicity (A. N. Heinloth et al., 2004, Toxicol. Sci. 80, 193-202).Toxicological Sciences 01/2006; 88(2):585-601. · 4.65 Impact Factor -
Article: Identification of putative gene based markers of renal toxicity.
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ABSTRACT: This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants--cisplatin, gentamicin, and puromycin--to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for 21 days), gentamicin (2-240 mg/kg/day for 7 days), or a single dose of cisplatin (0.1-5 mg/kg). Groups of rats were sacrificed at various times after administration of these compounds for standard clinical chemistry, urine analysis, and histological evaluation of the kidney. RNA was extracted from the kidney for microarray analysis. Principal component analysis and gene expression-based clustering of compound effects confirmed sample separation based on dose, time, and degree of renal toxicity. In addition, analysis of the profile components revealed some novel changes in the expression of genes that appeared to be associated with injury in specific portions of the nephron and reflected the mechanism of action of these various nephrotoxicants. For example, although puromycin is thought to specifically promote injury of the podocytes in the glomerulus, the changes in gene expression after chronic exposure of this compound suggested a pattern similar to the known proximal tubular nephrotoxicants cisplatin and gentamicin; this prediction was confirmed histologically. We conclude that renal gene expression profiling coupled with analysis of classical end points affords promising opportunities to reveal potential new mechanistic markers of renal toxicity.Environmental Health Perspectives 04/2004; 112(4):465-79. · 7.04 Impact Factor -
Article: Overview on the application of transcription profiling using selected nephrotoxicants for toxicology assessment.
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ABSTRACT: Microarrays allow for the simultaneous measurement of changes in the levels of thousands of messenger RNAs within a single experiment. As such, the potential for the application of transcription profiling to preclinical safety assessment and mechanism-based risk assessment is profound. However, several practical and technical challenges remain. Among these are nomenclature issues, platform-specific data formats, and the lack of uniform analysis methods and tools. Experiments were designed to address biological, technical, and methodological variability, to evaluate different approaches to data analysis, and to understand the application of the technology to other profiling methodologies and to mechanism-based risk assessment. These goals were addressed using experimental information derived from analysis of the biological response to three mechanistically distinct nephrotoxins: cisplatin, gentamicin, and puromycin aminonucleoside. In spite of the technical challenges, the transcription profiling data yielded mechanistically and topographically valuable information. The analyses detailed in the articles from the Nephrotoxicity Working Group of the International Life Sciences Institute Health and Environmental Sciences Institute suggest at least equal sensitivity of microarray technology compared to traditional end points. Additionally, microarray analysis of these prototypical nephrotoxicants provided an opportunity for the development of candidate bridging biomarkers of nephrotoxicity. The potential future extension of these applications for risk assessment is also discussed.Environmental Health Perspectives 04/2004; 112(4):460-4. · 7.04 Impact Factor
