Project description:Multiple accidents in nuclear power plants and growing concerns in misuse of radiation exposure in warfare have called for rapid determination of radiation exposure and the chances to survive. Latest findings about circulating microRNA (miRNAs) using several animal models revealed considerable promises, although translating this knowledge to clinics remains a major challenge. To address this issue, we randomly divided 36 non-human primates (NHPs) into six equal groups and each group was exposed to six radiation doses from 6 Gy to 8.5 Gy with 0.5 Gy incremental order. Serum samples were collected pre-total body irradiation (TBI) and three timepoints afterwards namely, day 1, 2 and 6 post-TBI. Global microRNA (miRNA) reads were generated from deep sequencing platform and to increase the translational potential, we diligently aligned the miRNA sequences and functional responses of NHPs to human following an in silico routine. Those miRNAs, which were sequentially and functionally conserved between human and NHPs were curated to meet two primary objectives. First to find the molecular dynamics correlated to radiation dosimetry and second to find putative markers to predict the risk to radiation-induced fatality (RRiF). Multi-variate differential analysis identified dosimetry-miRNA markers that consistently regulated with increasing dose but independent of the time since irradiation (TSI). Likewise, a set of potential TSI-markers were identified that consistently shifted their regulations with increasing TSI, but independent of dosimetry. Functional analysis found a considerable gender bias in low range of dosimetry, but at high dose, when the RRiF increased, the bionetworks across the sexes operated in sync. Bionetworks linked to cell quantity and cell invasion significantly altered between the survived and decedent cohort. Proprietary algorithm identified candidate models with a few miRNAs that can predict RRiF with >80% AUC. An assay could be conceptualized from this putative RRiF panel supplemented with the dose-/TSI-markers to predict RRiF with high confidence.
Project description:This SuperSeries is composed of the following subset Series: GSE6871: Gene expression signatures that predict radiation exposure (human) GSE6873: Gene expression signatures that predict radiation exposure (mouse) Keywords: SuperSeries Refer to individual Series
Project description:Gene expression analysis of peripheral blood leukocytes (PB MNCs) to develop expression profiles that accurately reflect prior radiation exposure. Keywords: Comparative, exposure dosage, C57BI6 Murine Irradiation Studies We have made use of gene expression analysis of peripheral blood mononuclear cells (PB MNCs) to develop expression profiles that accurately reflect prior radiation exposure. Importantly, we demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, ranging from 50 cGy to 1000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from non-irradiated samples with an accuracy of 90%, sensitivity of 85% and specificity of 94%. We further demonstrate that a radiation profile developed in the mouse can correctly distinguish PB samples from irradiated and non-irradiated human patients with an accuracy of 77%, sensitivity of 82% and specificity of 75%. Taken together, these data demonstrate that molecular profiles can be generated which are highly predictive of different levels of radiation exposure in mice and humans. Mouse Dataset only
Project description:Exposure to high-dose radiation causes life-threatening serious intestinal damage. Histological analysis is the most accurate method for judging the extent of intestinal damage after death. However, it is difficult to predict the extent of intestinal damage to body samples. Here we focused on extracellular microRNAs (miRNAs) released from cells and investigated miRNA species that increased or decreased in serum and feces using a radiation-induced intestinal injury mouse model. A peak of small RNA of 25–200 nucleotides was detected in mouse serum and feces 72 h after radiation exposure, and miRNA presence in serum and feces was inferred. MiRNAs expressed in the small intestine and were increased by more than 2.0-fold in serum or feces following a 10 Gy radiation exposure were detected by microarray analysis and were 4 in serum and 19 in feces. In this study, miR-375-3p, detected in serum and feces, was identified as the strongest candidate for a high-dose radiation biomarker in serum and/or feces using a radiation-induced intestinal injury model.
Project description:The extreme radiation resistance of Deinococcus bacteria requires the radiation-stimulated cleavage of protein DdrO by a specific metalloprotease called IrrE. DdrO is the repressor of a predicted radiation/desiccation response (RDR) regulon, composed of radiation-induced genes having a conserved DNA motif (RDRM) in their promoter regions. Here, we showed that addition of zinc ions to purified apo-IrrE, and short exposure of Deinococcus cells to zinc ions, resulted in cleavage of DdrO in vitro and in vivo, respectively. Binding of IrrE to RDRM-containing DNA or interaction of IrrE with DNA-bound DdrO was not observed. The data are in line with IrrE being a zinc peptidase, and indicate that increased zinc availability, caused by oxidative stress, triggers the in vivo cleavage of DdrO unbound to DNA. Transcriptomics and proteomics of Deinococcus deserti confirmed the IrrE-dependent regulation of predicted RDR regulon genes and also revealed additional members of this regulon. Comparative analysis showed that the RDR regulon is largely well conserved in Deinococcus species, but also showed diversity in the regulon composition. Notably, several RDR genes with an important role in radiation resistance in Deinococcus radiodurans, for example pprA, are not conserved in some other radiation-resistant Deinococcus species.
Project description:To investigate whether circRNAs have the potential for being radiation biomarker,we screened the radiation-induced differential expressed circRNAs in the AHH-1 cell line exposed to 60Co γ rays. And we established 4 expression models for radiation dose estimation by use of the validated radiation-induced differential expressed circRNAs.