A frequency-based gene selection method to identify robust biomarkers for radiation dose prediction

Boldt, Sonja; Knops, Katja; Kriehuber, Ralf; Wolkenhauer, Olaf

doi:10.3109/09553002.2012.638358

Cited by 39 publications

(42 citation statements)

References 37 publications

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“…All non-irradiated samples were correctly classified as unirradiated controls by the KNN method. Overall, the obtained dose estimations obtained by KNN classification were very satisfying keeping in mind that the classification is not based on the calibration sample data but on microarray data from 2008-2011 derived from cultured peripheral blood lymphocytes from six nonrelated blood donors (for more detail, see Boldt et al 2012).…”

Section: Dose Estimationmentioning

confidence: 63%

“…It has been reported many times that the quantification of gene expression in response to radiation exposure by microarray technology is robust and reliable (Paul & Amundson 2008;Boldt et al 2012;Knops et al 2012), and the obtained gene signatures derived in ex situ irradiated blood are shown to be predictive for the radiation dose in vitro as well as in vivo (Paul et al 2011). The gene signature developed by Boldt et al (2012) was reported to be robust in terms of dose prediction.…”

Section: Discussionmentioning

confidence: 97%

“…Donor variability and variability among male and females has been previously addressed in human blood Afterwards, the test sample was assigned to the most frequent radiation dose among its three nearest neighbours. The training samples were derived from ex-situ irradiated blood from six non-related healthy donors (three males and three females of three age classes; Boldt et al 2012). Gene expression of FDXR and TNFSF4 are given as Log2 values.…”

Section: Discussionmentioning

confidence: 99%

“…Dose assessment in irradiated blood samples can be obtained by either using dose predictive gene or exon signatures (Paul & Amundson 2008;Kabacik et al 2011;Boldt et al 2012;Knops et al 2012;Lucas et al 2014;Macaeva et al 2016) or by monitoring the modification of transcription of single radiation-responsive genes like ferredoxin reductase (FDXR) (Manning et al 2013;Abend et al 2016).…”

Section: Introductionmentioning

confidence: 99%

“…In ex vivo studies, several protocols have been used such as cultured peripheral blood mononuclear cells (PBMC) (Dressman et al 2007;Meadows et al 2008Meadows et al , 2010Sprung et al 2011;Boldt et al 2012;Knops et al 2012;Riecke et al 2012;Macaeva et al 2016), cultured whole blood diluted with media Brzoska andKruszewski 2015, Abend et al 2016) or undiluted whole blood (Manning et al 2013). However, none of these studies have addressed the role of blood culture methods during the incubation time at 37 C following radiation exposure.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Comparable dose estimates of blinded whole blood samples are obtained independently of culture conditions and analytical approaches. Second RENEB gene expression study

Manning

Macaeva

Majewski

et al. 2016

International Journal of Radiation Biology

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Purpose: This collaboration of five established European gene expression labs investigated the potential impact of culture conditions on the transcriptional response of peripheral blood to radiation exposure. Materials and methods: Blood from one healthy donor was exposed ex vivo to a Cobalt 60 source to produce a calibration curve in addition to four unknown doses. After exposure, the blood samples were either diluted with RPMI medium or left untouched. After 24-h incubation at 37 C the diluted blood samples were lysed, while the undiluted samples were mixed with the preservative RNALater and all samples were shipped frozen to the participating labs. Samples were processed by each lab using microarray (one lab) and QRT-PCR (four labs). Results: We show that although culture conditions affect the total amount of RNA recovered (p < .0001) and its integrity (p < .0001), it does not significantly affect dose estimates (except for the true dose at 1.1 Gy). Most importantly, the different analysis approaches provide comparable mean absolute difference of estimated doses relative to the true doses (p ¼ .9) and number of out of range (>0.5 Gy) measurements (p ¼ .6). Conclusion: This study confirms the robustness of gene expression as a method for biological dosimetry. ARTICLE HISTORY

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Section: Dose Estimationmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Comparable dose estimates of blinded whole blood samples are obtained independently of culture conditions and analytical approaches. Second RENEB gene expression study

Manning

Macaeva

Majewski

et al. 2016

International Journal of Radiation Biology

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Effect of irradiation on the expression of DNA repair genes studied in human fibroblasts by real-time qPCR using three methods of reference gene validation

Reuther

Reiter

Raabe

et al. 2013

Radiat Environ Biophys

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The aim of this study was to determine the effects of ionizing radiation on gene expression by using for a first time a qPCR platform specifically established for the detection of 94 DNA repair genes but also to test the robustness of these results by using three analytical methods (global pattern recognition, ΔΔCq/Normfinder and ΔΔCq/Genorm). Study was focused on these genes because DNA repair is known primarily to determine the radiation response. Six strains of normal human fibroblasts were exposed to 2 Gy, and changes in gene expression were analyzed 24 h thereafter. A significant change in gene expression was found for only few genes, but the genes detected were mostly different for the three analytical methods used. For GPR, a significant change was found for four genes, in contrast to the eight or nine genes when applying ΔΔCq/Genorm or ΔΔCq/Normfinder, respectively. When using all three methods, a significant change in expression was only seen for GADD45A and PCNA. These data demonstrate that (1) the genes identified to show an altered expression upon irradiation strongly depend on the analytical method applied, and that (2) overall GADD45A and PCNA appear to play a central role in this response, while no significant change is induced for any of the other DNA repair genes tested.

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Toward the development of transcriptional biodosimetry for the identification of irradiated individuals and assessment of absorbed radiation dose

Brzóska

Kruszewski

2015

Radiat Environ Biophys

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The most frequently used and the best established method of biological dosimetry at present is the dicentric chromosome assay, which is poorly suitable for a mass casualties scenario. This gives rise to the need for the development of new, high-throughput assays for rapid identification of the subjects exposed to ionizing radiation. In the present study, we tested the usefulness of gene expression analysis in blood cells for biological dosimetry. Human peripheral blood from three healthy donors was X-irradiated with doses of 0 (control), 0.6, and 2 Gy. The mRNA level of 16 genes (ATF3, BAX, BBC3, BCL2, CDKN1A, DDB2, FDXR, GADD45A, GDF15, MDM2, PLK3, SERPINE1, SESN2, TNFRSF10B, TNFSF4, and VWCE) was assessed by reverse transcription quantitative PCR 6, 12, 24, and 48 h after exposure with ITFG1 and DPM1 used as a reference genes. The panel of radiation-responsive genes was selected comprising GADD45A, CDKN1A, BAX, BBC3, DDB2, TNFSF4, GDF15, and FDXR. Cluster analysis showed that ΔCt values of the selected genes contained sufficient information to allow discrimination between irradiated and non-irradiated blood samples. The samples were clearly grouped according to the absorbed doses of radiation and not to the time interval after irradiation or to the blood donor.Electronic supplementary materialThe online version of this article (doi:10.1007/s00411-015-0603-8) contains supplementary material, which is available to authorized users.

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A frequency-based gene selection method to identify robust biomarkers for radiation dose prediction

Abstract: The genes identified are potential robust biomarkers, which are particularly suitable for dose level discrimination at a window of time that would be appropriate for life-saving medical triage.

Cited by 39 publications

References 37 publications

Comparable dose estimates of blinded whole blood samples are obtained independently of culture conditions and analytical approaches. Second RENEB gene expression study

Comparable dose estimates of blinded whole blood samples are obtained independently of culture conditions and analytical approaches. Second RENEB gene expression study

Effect of irradiation on the expression of DNA repair genes studied in human fibroblasts by real-time qPCR using three methods of reference gene validation

Toward the development of transcriptional biodosimetry for the identification of irradiated individuals and assessment of absorbed radiation dose

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