Biomarker Qualification – Past, Present and Future

Abstract Against the backdrop of the launch of the Human Genome Project, scientists from a variety of industries, academia and governmental organizations convened in late 1998 under the sponsorship of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) to deliberate on how best to advance the promising field of toxicogenomics. The landmark undertaking to sequence the human genome was enabled by the emergence of a variety of approaches and platforms for measuring changes in the expressions of thousands of genes simultaneously, and there was widespread interest in the toxicology community in applying this knowledge and the emerging technologies to safety assessment. This chapter describes the role played by the Health and Environmental Sciences Institute (HESI) Committee on the Application of Genomics to Mechanism-based Risk Assessment (HESI Genomics Committee) in facilitating a cross-industry, government and academic effort to explore the utility of genomics methods and technologies for improving the understanding of mechanisms of toxicity and advancing risk assessment, and its contributions to the development of multi-site biomarker validation approaches.

[1]  Lee Bennett,et al.  Gene expression analysis reveals chemical-specific profiles. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[2]  R. Ulrich,et al.  Overview of an interlaboratory collaboration on evaluating the effects of model hepatotoxicants on hepatic gene expression. , 2004, Environmental health perspectives.

[3]  Michael D Waters,et al.  Database development in toxicogenomics: issues and efforts. , 2004, Environmental health perspectives.

[4]  J. Waring,et al.  Clofibrate-induced gene expression changes in rat liver: a cross-laboratory analysis using membrane cDNA arrays. , 2004, Environmental health perspectives.

[5]  Jiri Aubrecht,et al.  The utility of DNA microarrays for characterizing genotoxicity. , 2004, Environmental health perspectives.

[6]  P. Bushel,et al.  Discovery in toxicology: Mediation by gene expression array technology , 2001, Journal of biochemical and molecular toxicology.

[7]  Timothy A Bertram,et al.  Identification of putative gene based markers of renal toxicity. , 2004, Environmental health perspectives.

[8]  J. Kleinjans,et al.  Moving Forward in Human Cancer Risk Assessment , 2010, Environmental health perspectives.

[9]  F. Staedtler,et al.  Perturbation of microRNAs in Rat Heart during Chronic Doxorubicin Treatment , 2012, PloS one.

[10]  John Quackenbush,et al.  Sources of variation in baseline gene expression levels from toxicogenomics study control animals across multiple laboratories , 2008, BMC Genomics.

[11]  Kerry Blanchard,et al.  Methapyrilene Toxicity: Anchorage of Pathologic Observations to Gene Expression Alterations , 2002, Toxicologic pathology.

[12]  Shibing Deng,et al.  Characterization and interlaboratory comparison of a gene expression signature for differentiating genotoxic mechanisms. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[13]  William Pennie,et al.  Toxicogenomics in risk assessment: an overview of an HESI collaborative research program. , 2004, Environmental health perspectives.

[14]  Krishna Prasad,et al.  Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium , 2010, Nature Biotechnology.

[15]  Michael L Bittner,et al.  Stress-specific signatures: expression profiling of p53 wild-type and -null human cells , 2005, Oncogene.

[16]  Raegan B O'Lone,et al.  Sources of variance in baseline gene expression in the rodent liver. , 2012, Mutation research.

[17]  P. S. Pine,et al.  Dye bias correction in dual-labeled cDNA microarray gene expression measurements. , 2004, Environmental health perspectives.

[18]  R G Ulrich,et al.  Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles. , 2001, Toxicology and applied pharmacology.

[19]  Quantitative PCR deconstruction of discrepancies between results reported by different hybridization platforms. , 2004, Environmental health perspectives.

[20]  G. Warnes,et al.  Differentiation of DNA reactive and non-reactive genotoxic mechanisms using gene expression profile analysis. , 2004, Mutation research.

[21]  J. Waring,et al.  Interlaboratory evaluation of rat hepatic gene expression changes induced by methapyrilene. , 2004, Environmental health perspectives.

[22]  Ivan Rusyn,et al.  Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans. , 2009, Genome research.

[23]  Zhaomei Zhang,et al.  An integrative genomic analysis identifies Bhmt2 as a diet-dependent genetic factor protecting against acetaminophen-induced liver toxicity. , 2010, Genome research.

[24]  Jiri Aubrecht,et al.  Voluntary exploratory data submissions to the US FDA and the EMA: experience and impact , 2010, Nature Reviews Drug Discovery.

[25]  L. Hood,et al.  Circulating microRNAs, potential biomarkers for drug-induced liver injury , 2009, Proceedings of the National Academy of Sciences.