Gene Expression
Identification of a Gene Expression Pattern as Clinical Predictor of Toxic Exposure
A review of Blood gene expression signatures predict exposure levels.
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
Bushel et al (2007) demonstrate that gene expression data from peripheral blood cells can more accurately predict levels of exposure to a harmful substance than clinical chemistry, hematology or histophathology. By applying classifier prediction algorithms, the authors identified 270 differentially expressed genes between rats exposed to toxic and nontoxic levels of acetaminophen. Using Agilent’s human and rat microarrays, the researchers studied a subset of 66 genes to look for expression signatures between exposure groups. The expression profiles of the predictor genes from the patterns extracted from the blood exhibited remarkable (97% accuracy) transtissue acetaminophen (APAP) exposure prediction when liver gene expression data were used as a test set. Analysis of human samples revealed separation of APAP-intoxicated patients from control individuals based on blood expression levels of human orthologs of the rat discriminatory genes. The results of this study support the use of genomic markers in the blood as surrogates for clinical markers of potential acute liver damage.
Figure 1. Workflow to predict the exposure level of the samples. The steps in the classifier-based and pattern-based approaches are shown.
Figure 2. Differentially expressed genes in blood that discriminate between exposure to subtoxic/nontoxic or toxic dose of APAP. Pictured is a subgroup of genes involved in immune response and inflammation. Gray filling of circles beside genes indicates identification of genes in the list of discriminatory genes (top circle, EPIG; middle circle, k-NN, bottom circle, ANOVA DME and DCE), and coloring of squares signals direction of change (red, up-regulation; green, down-regulation in comparison with mock-treated control).
Title: : Blood gene expression signatures predict exposure levels.
Journal: Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18211-18216.
Authors: Bushel PR, Heinloth AN, Li J, Huang L, Chou JW, Boorman GA, Malarkey DE, Houle CD, Ward SM, Wilson RE, Fannin RD, Russo MW, Watkins PB, Tennant RW, Paules RS
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