Summary of Study ST001892

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, 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.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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.
Institute
Georgetown University
Last NamePannkuk
First NameEvan
Address3970 Reservoir Rd, NW New Research Building E504
Emailelp44@georgetown.edu
Phone2026875650
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
https://dx.doi.org/10.21228/M8RM4F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype_irradiation
SA17595326dki_2Gy
SA17595424dki_2Gy
SA17595527dki_2Gy
SA17595629dki_2Gy
SA17595731dki_2Gy
SA17595830dki_2Gy
SA17595925dki_2Gy
SA17596028dki_2Gy
SA17596133dki_7Gy
SA17596237dki_7Gy
SA17596336dki_7Gy
SA17596435dki_7Gy
SA17596534dki_7Gy
SA17596632dki_7Gy
SA17596742dki_7Gy
SA17596843dki_7Gy
SA17596944dki_7Gy
SA17597038dki_7Gy
SA17597141dki_7Gy
SA17597240dki_7Gy
SA17597339dki_7Gy
SA17597423dki_sham
SA17597517dki_sham
SA17597616dki_sham
SA17597718dki_sham
SA17597819dki_sham
SA17597921dki_sham
SA17598020dki_sham
SA17598122dki_sham
SA1759386WT_2Gy
SA1759398WT_2Gy
SA17594010WT_2Gy
SA1759417WT_2Gy
SA1759429WT_2Gy
SA17594312WT_7Gy
SA17594414WT_7Gy
SA17594513WT_7Gy
SA17594611WT_7Gy
SA17594715WT_7Gy
SA1759482WT_sham
SA1759491WT_sham
SA1759505WT_sham
SA1759513WT_sham
SA1759524WT_sham
Showing results 1 to 44 of 44
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