Development of phenotypic and transcriptional biomarkers to evaluate relative activity of potentially estrogenic chemicals in ovariectomized mice.

Background: Concerns regarding potential endocrine-disrupting chemicals (EDCs) have led to a need for methods to evaluate candidate estrogenic chemicals. Our previous evaluations of two such EDCs revealed a response similar to that of estradiol (E2) at 2 hr, but a less robust response at 24 hr, similar to the short-acting estrogen estriol (E3).

Objectives: Microarray analysis using tools to recognize patterns of response have been utilized in the cancer field to develop biomarker panels of transcripts for diagnosis and selection of treatments most likely to be effective.

Transcriptional responses to loss of RNase H2 in Saccharomyces cerevisiae.

We report here the transcriptional responses in Saccharomyces cerevisiae to deletion of the RNH201 gene encoding the catalytic subunit of RNase H2. Deleting RNH201 alters RNA expression of 349 genes by ≥1.5-fold (q-value <0.

The impact of classification of interest on predictive toxicogenomics.

The era of toxicogenomics has introduced a new way of monitoring the effect of environmental stressors and toxicants on biological systems via quantification of changes in gene expression. Because the liver is one of the major organs for synthesis and secretion of substances which metabolize endogenous and exogenous materials, there has been a great deal of interest in elucidating predictive and mechanistic genomic markers of hepatotoxicity. This mini-review will bring context to a limited number of toxicogenomics studies which used genomics to evaluate the transcriptional changes in blood and liver in response to acetaminophen (APAP) or other liver toxicants, but differed according to the classification of interest (COI), i.

Principal component analysis-based filtering improves detection for Affymetrix gene expression arrays.

Gene expression array technology has reached the stage of being routinely used to study clinical samples in search of diagnostic and prognostic biomarkers. Due to the nature of array experiments, which examine the expression of tens of thousands of genes simultaneously, the number of null hypotheses is large. Hence, multiple testing correction is often necessary to control the number of false positives.

Microarray analysis of ethanol-induced changes in gene expression.

DNA microarray studies offer a robust method for nonbiased analysis of whole genome messenger ribonucleic acid expression patterns. A growing number of studies have applied this experimental approach to studies on ethanol either in cell culture of animal models of ethanol exposure or self-administration. Expression profiling has identified novel gene networks responding to ethanol or differing across animal strains with differing responses to ethanol.

SScore: an R package for detecting differential gene expression without gene expression summaries.

Summary: SScore is an R package that facilitates the comparison of gene expression between Affymetrix GeneChips using the S-score algorithm. The S-score algorithm uses probe level data directly to assess differences in gene expression, without requiring a preliminary separate step of probe set expression summary estimation. Therefore, the algorithm avoids introduction of error associated with the expression summary estimation process and has been demonstrated to improve the accuracy of identifying differentially expressed genes.

DNA microarray and proteomic strategies for understanding alcohol action.

This article summarizes the proceedings of a symposium presented at the 2005 annual meeting of the Research Society on Alcoholism in Santa Barbara, California. The organizer was James M. Sikela, and he and Michael F.

Identification of DHBcAg as a potent carrier protein comparable to KLH for augmenting MUC1 antigenicity.

MUC1 is expressed at the cell surface of epithelial cancers. We have shown previously that MUC1 conjugated to keyhole limpet hemocyanin (KLH) plus the saponin immunological adjuvant QS-21 induces consistent high titer IgM and IgG antibodies in patients after treatment of their primary or metastatic cancers. KLH however is poorly soluble and heterogeneous making it difficult to work with, and we hypothesize that changing carrier proteins mid-way through a vaccination schedule would further increase antibody titers.

Ethanol-responsive brain region expression networks: implications for behavioral responses to acute ethanol in DBA/2J versus C57BL/6J mice.

Activation of the mesolimbic dopamine reward pathway by acute ethanol produces reinforcement and changes in gene expression that appear to be crucial to the molecular basis for adaptive behaviors and addiction. The inbred mouse strains DBA/2J and C57BL/6J exhibit contrasting acute behavioral responses to ethanol. We used oligonucleotide microarrays and bioinformatics methods to characterize patterns of gene expression in three brain regions of the mesolimbic reward pathway of these strains.

Alcohol effects on central nervous system gene expression in genetic animal models.

This article summarizes the proceedings of a symposium presented at the 2004 annual meeting of the Research Society on Alcoholism in Vancouver, British Columbia, Canada. The organizers and chairs were William J. McBride and Michael F.

Application of the S-score algorithm for analysis of oligonucleotide microarrays.

In the past several years, oligonucleotide microarrays have emerged as a widely used tool for the simultaneous, non-biased measurement of expression levels for thousands of genes. Several challenges exist in successfully utilizing this biotechnology; principal among these is analysis of microarray data. An experiment to measure differential gene expression can consist of a dozen microarrays, each consisting of over a hundred thousand data points.