Gene expression signatures that predict radiation exposure in mice and humans.
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BACKGROUND: The capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation. METHODS AND FINDINGS: We have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. 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 1,000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from nonirradiated 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 nonirradiated 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 that are highly predictive of different levels of radiation exposure in mice and humans. CONCLUSIONS: We suggest that this approach, with additional refinement, could provide a method to assess the effects of various environmental inputs into biological phenotypes as well as providing a more practical application of a rapid molecular screening test for the diagnosis of radiation exposure.
Dose-Response Relationship, Radiation
Gene Expression Profiling
Gene Regulatory Networks
Mice, Inbred C57BL
Oligonucleotide Array Sequence Analysis
Radiation Injuries, Experimental
Sensitivity and Specificity
Published Version (Please cite this version)10.1371/journal.pmed.0040106
Publication InfoChao, Nelson J; Chute, JP; Dressman, HK; Ginsburg, Geoffrey Steven; Marshall, D; Meadows, Sarah K; ... Nevins, JR (2007). Gene expression signatures that predict radiation exposure in mice and humans. PLoS Med, 4(4). pp. e106. 10.1371/journal.pmed.0040106. Retrieved from http://hdl.handle.net/10161/11574.
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Donald D. and Elizabeth G. Cooke Cancer Research Professor
My research interests are in two broad areas, clinical hematopoietic stem cell and cord blood transplantation and in the laboratory studies related to graft vs. host disease and immune reconstitution. On the clinical side we are currently conducting approximately 50 different clinical protocols ranging from preparatory regimens, supportive care studies and disease specific protocols. Most of these clinical studies are centered around studies of the sources of stem cells and the methods to
Professor of Medicine
Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.
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Akleyev, AV; Akushevich, Igor; Arbeev, Konstantin; Dimov, GP; Ukraintseva, Svetlana; Veremeyeva, Galina A; Yashin, Anatoli I (Radiat Environ Biophys, 2011-05)A new model of the hematopoietic system response in humans chronically exposed to ionizing radiation describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the four blood cell ...
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Gene expression signatures of radiation response are specific, durable and accurate in mice and humans. Chao, Nelson J; Chute, JP; Dressman, HK; Ginsburg, Geoffrey Steven; Himburg, Heather; Meadows, Sarah K; Muramoto, Garrett G; ... (10 authors) (PLoS One, 2008-04-02)BACKGROUND: Previous work has demonstrated the potential for peripheral blood (PB) gene expression profiling for the detection of disease or environmental exposures. METHODS AND FINDINGS: We have sought to determine the ...