Summary of Study ST001891
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.
| Study ID | ST001891 |
| Study Title | Small molecule signatures of mice lacking T-cell p38 alternate activation, a model for immunosuppression conditions, after exposure to total body radiation (part I) |
| Study Summary | Introduction 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 Name | Pannkuk |
| First Name | Evan |
| Address | 3970 Reservoir Rd, NW New Research Building E504 |
| elp44@georgetown.edu | |
| Phone | 2026875650 |
| Submit Date | 2021-07-23 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Waters) |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-07-06 |
| Release Version | 1 |
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Sample Preparation:
| Sampleprep ID: | SP001975 |
| Sampleprep Summary: | Biofluids were prepared as previously described (Pannkuk et al. 2018;2020). Urine (20 μl) was deproteinated with 50% acetonitrile (80 μl) containing internal standards (2 μM debrisoquine sulfate, 30 μM 4-nitrobenzoic acid), incubated on ice for 10 min, vortexed for 30 seconds, and centrifuged for 10 min (10,000 x g, 4°C). Serum (5 μl) was prepared as above but was deproteinated with 66% acetonitrile (195 μl). A quality control (QC) sample was prepared by mixing 1 μl from each sample and prepared as above. |
| Processing Storage Conditions: | -80℃ |
