Murine gene expression profiles do not predict human radiation status.

<p>A) A Minority of Murine Radiation Response Genes Are Expressed in Humans. The scatterplot shows –log (P-value) for a Pearson test of correlation between radiation exposure dose and gene expression for each gene with a mouse-human analog. If mouse (y-axis) and human (x-axis) were identifying the same genes, then we would expect that the points would fall on a diagonal line. Approximately 9,000 mouse genes have clear human analogues on the U133A microarray. 3,353 genes have significant association with dose (p-value <.05 after correction for multiple testing). Of those, 109 genes are significantly associated in humans. B) Performance of the Murine Radiation Classifier Against Human PB Samples. We used penalized regression with individual genes as potential independent variables to build a model predicting radiation exposure dose in mice. However, using variable selection to build models that predict radiation in mice does not lead to models that predict radiation exposure in humans. <i>Panel i</i> shows the mean predicted radiation levels (+/− SEM) of human <i>ex vivo</i> irradiated blood samples at 6 hrs and 24 hrs. <i>Panel ii</i> shows the mean predicted radiation levels of human TBI patient samples. The x-axis shows the times after irradiation at which gene expression measurements were taken. Actual radiation doses are displayed by different colors. Note the overlap between predicted mean radiation values in each analysis.</p

A 15-gene classifier can predict radiation dose levels in mice.

<p>A) C57Bl6 mice were irradiated with the TBI dose levels indicated (colors shown) and PB was collected at the times post-irradiation shown on the X axis. The Y axis shows the radiation dose levels predicted by application of the classifier against the irradiated samples. Each dot represents the mean dose level with corresponding 99% confidence intervals about the mean. As shown, at each dose level tested and at every time point through 7 days (168 hrs), the classifier discriminated radiation dose with high accuracy. B) Neither GCSF nor LPS treatments confound the predictive capability of the classifier to predict murine radiation dose levels. The predicted radiation dose levels (y axis) are plotted against time (x axis) of murine PB samples treated with and without GCSF and LPS. C) The RMA normalized gene expression levels of i) IGH-6, ii) LOXL1 and iii) CDKN1A are shown over time following several different radiation dose levels in mice and <i>ex vivo</i> with and without LPS treatment. While IGH-6 expression decreased in response to irradiation, LOXL1 expression increased promptly and CDKN1A was a late responsive gene.</p

Human Radiation Genes.

<p>Human Radiation Genes.</p

CLPA Assay Reagents.

<p>CLPA Assay Reagents.</p

The CLPA assay predicts the radiation status of human PB samples with high accuracy.

<p>A) A schematic representation of the CLPA assay is shown. B) Scatter plots are shown of the predicted radiation dose levels of human PB samples (y axis) which were irradiated <i>ex vivo</i> with the radiation dose levels shown on the x axis. C) Scatter plots are shown of the predicted radiation dose levels of PB samples from human TBI patients (y axis) who were irradiated with the dose levels shown on the x axis. n = 7 patient samples in each group.</p

CLPA Assay Genes.

<p>CLPA Assay Genes.</p