Example of fitted spline regression models.

<p>The plot shows spline regression models fitted to the measured time-course expression data of an arbitrary chosen gene (BBC3). The blue line represents the fitted model for the control (0 Gy) and read line that for the irradiated group (1 Gy). Blue and red dots represent the measured expression levels of the biological replicates. Vertical lines represent the endpoints and interior knots correspond to the 0.33- and 0.66-quantiles.</p

Comparison of NCSRM and BETR methods with respect to the top 10 pathways after mapping of 5% highest ranked genes from the reconstructed gene association networks.

Comparison of NCSRM and BETR methods with respect to the top 10 pathways after mapping of 5% highest ranked genes from the reconstructed gene association networks.</p

Ionizing radiation biomarkers in epidemiological studies –An update

Recent epidemiology studies highlighted the detrimental health effects of exposure to low dose and low dose rate ionizing radiation (IR): nuclear industry workers studies have shown increased leukaemia and solid tumour risks following cumulative doses of <100mSv and dose rates of <10mGy per year; paediatric patients studies have reported increased leukaemia and brain tumours risks after doses of 30-60mGy from computed tomography scans. Questions arise, however, about the impact of even lower doses and dose rates where classical epidemiological studies have limited power but where subsets within the large cohorts are expected to have an increased risk. Further progress requires integration of biomarkers or bioassays of individual exposure, effects and susceptibility to IR. The European DoReMi (Low Dose Research towards Multidisciplinary Integration) consortium previously reviewed biomarkers for potential use in IR epidemiological studies. Given the increased mechanistic understanding of responses to low dose radiation the current review provides an update covering technical advances and recent studies. A key issue identified is deciding which biomarkers to progress. A roadmap is provided for biomarker development from discovery to implementation and used to summarise the current status of proposed biomarkers for epidemiological studies. Most potential biomarkers remain at the discovery stage and for some there is sufficient evidence that further development is not warranted. One biomarker identified in the final stages of development and as a priority for further research is radiation specific mRNA transcript profiles

Number of genes subjected to GAN reconstruction and properties of resulted GANs.

<p>Number of genes subjected to GAN reconstruction and properties of resulted GANs.</p

Schematic workflow of the analysis of gene expression time-course data.

<p>Samples were collected 0.25, 0.5, 1, 2, 4, 8 and 24 hours after sham or actual irradiation. Transcriptional profiling was performed using Agilent gene expression microarrays and comprises three major steps: the identification of differentially expressed genes from time-course expression data by employing a natural cubic spline regression model; the use of regularized dynamic partial correlation method to infer gene associations networks from differentially expressed genes and the topological identification and functional characterization of the key nodes in the reconstructed networks.</p

Comparison of hub genes in networks resulting from different methods.

<p>Comparison of hub genes in networks resulting from different methods.</p

Number of detected and differentially expressed genes for each dose and cell lines for NCSRM and BETR methods.

<p>Number of detected and differentially expressed genes for each dose and cell lines for NCSRM and BETR methods.</p

γH2AX: Immunohistochemistry.

<p>Using antibodies against γH2AX and Alexa488 (green) as secondary antibody, we demonstrate that γH2AX is expressed, where DNA degradation during terminal differentiation of lens fiber cells occurs; these sites represent DNA double strand breaks. Cell nuclei are counterstained by DAPI (blue); presence of γH2AX in the cell nuclei is indicated by overlapping colors of blue and green resulting in yellow.</p

Confirmation of the <i>Ercc2</i> mutation by restriction digest.

<p>The novel <i>Mwo</i>I restriction site is present in all homozygous mutant mice tested. It is absent in 5 tested wild-type strains indicating that it is a mutation and no widespread polymorphism. The schema above the gels explains the digestion pattern of the fragment.</p

<i>RCO015</i> mutants and identification of the underlying mutation.

<p>a) A heterozygous (left) and homozygous (middle) <i>RCO015</i> mutant mouse at the age of 9 months compared to a wild type (right). The homozygous mutants are smaller and have rough hair and small eyes. b) Haplotype analysis defines the critical interval between the markers <i>116J6</i>.<i>1</i> and <i>D7Mit294</i> at mouse chromosome 7.</p