Summary of Study ST001892

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001191. The data can be accessed directly via it's Project DOI: 10.21228/M8RM4F This work is supported by NIH grant, U2C- DK119886.


This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001892
Study TitleSmall molecule signatures of mice lacking T-cell p38 alternate activation, a model for immunosuppression conditions, after exposure to total body radiation (part II)
Study SummaryIntroduction Novel biodosimetry assays are needed in the event of radiological/nuclear emergencies for both immediate triage and identifying delayed effects of acute radiation exposure. Genetically engineered mouse models are used to assess how genotypic variation in the general population may affect post-irradiation classification performance. Here, we used a mouse model that lacks the T-cell receptor specific alternative p38 pathway (p38αβY323F, double knock-in [DKI] mice) to determine how attenuated autoimmune and inflammatory responses may affect dose reconstruction. Objectives To determine if deficient alternative p38 activation differentially affects biofluid metabolic signatures post-irradiation compared to wild-type (WT). Methods Untargeted global metabolomics was used to assess biofluid signatures between WT and DKI mice (8 – 10 weeks old) after exposure to total body radiation (0, 2, or 7 Gy). Urine was analyzed in the first week (1, 3, and 7 d) and serum at 1 d. Spectral features of interest were identified using the machine learning algorithm Random Forests and MetaboLyzer. Validated metabolite panels were constructed and classification performance was assessed by determining the area under the receiver operating characteristic curve (AUROC). Results A multidimensional scaling plot showed excellent separation of IR exposed groups in WT with slightly dampened responses in DKI mice. For both urine and serum, excellent sensitivity and specificity (AUROC > 0.90) was observed for 0 Gy vs. 7 Gy groups irrespective of genotype using identical metabolite panels. Similarly, excellent to fair classification (AUROC > 0.75) was observed for ≤ 2 Gy vs. 7 Gy post-irradiation mice for both genotypes, however, model performance declined (AUROC < 0.75) between genotypes post-irradiation. Conclusion Overall, these results suggest less influence of the alternative p38 activation pathway for dose reconstruction compared to other radiosensitive genotypes.
Georgetown University
Last NamePannkuk
First NameEvan
Address3970 Reservoir Rd, NW New Research Building E504
Submit Date2021-07-23
Raw Data AvailableYes
Raw Data File Type(s)raw(Waters)
Analysis Type DetailLC-MS
Release Date2022-07-06
Release Version1
Evan Pannkuk Evan Pannkuk application/zip

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Treatment ID:TR001982
Treatment Summary:WT C57Bl/6 mice (C57BL/6NCrl strain code #027) were obtained from Charles River Laboratories (Frederick, MD) and DKI mice were kindly provided by the Laboratory of Immune Cell Biology, National Cancer Institute (P.I. Jonathan D. Ashwell, M.D.) (Jirmanova et al. 2011). Animals were bred/irradiated (12 h light / 12 h dark cycle conditions) at Georgetown University and water and food (PicoLab Rodent Diet 20 #5053) were provided ad libitum according to Georgetown University Institutional Animal Care and Use Committee (GUACUC) protocols (2016-1152). Before irradiation and biofluid collection the mice were acclimated to metabolic cages for 24 h. Male mice that were 8 – 10 weeks old were exposed to a total body ionization (TBI) x-ray dose (~1.67 Gy/min; X-Rad 320, Precision X-Ray Inc, Branford, CT; filter, 0.75 mm tin/ 0.25 mm copper/1.5 mm aluminum) of 0, 2, or 7 Gy. All urine samples were collected over a 24 h period in a metabolic cage pre-irradiation and at days 1, 3, and 7 d post-irradiation (Figure S1). Blood for metabolomics was collected at 1 d via cheek bleed from the submandibular vein and serum was separated in a BD microtainer serum separator tube and centrifuged for 10 min (10,000 x g, 4°C). Serum samples from sham-irradiated mice were used as a control (Figure S1). All biofluids were flash frozen and stored at -80°C until further use. Seven days post-irradiation, blood was collected in a dipotassium EDTA Tube (BD Cat #365974) via the facial vein from each animal and subjected to a complete blood count by VRL Diagnostics (Gaithersburg, MD, (Figure S2).