Summary of Study ST003334

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 PR002073. The data can be accessed directly via it's Project DOI: 10.21228/M8NR71 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 IDST003334
Study TitleImpact of partial body shielding from very high dose rates on untargeted metabolomics in biodosimetry
Study SummaryA realistic exposure to ionizing radiation (IR) from an improvised nuclear device will likely include individuals that are partially shielded from the initial blast delivered at a very high-dose rate (VHDR). As different tissues have varying levels of radiosensitivity, e.g. hematopoietic vs. gastrointestinal tissues, the effects of shielding on radiation biomarkers needs to be addressed. Here, we explore how biofluid (urine and serum) metabolite signatures from male and female C57BL/6 mice exposed to VHDR (5 – 10 Gy/sec) total body irradiation (TBI, 0, 4, and 8 Gy) compare to individuals exposed to partial body irradiation (PBI) (lower body irradiated [LBI] or upper body irradiated [UBI] at an 8 Gy dose) using a data-independent acquisition untargeted metabolomics approach. Although sex differences were observed in the spatial groupings of urine signatures from TBI and PBI mice, a metabolite signature (N6,N6,N6-trimethyllysine, carnitine, propionylcarnitine, hexosamine-valine-isoleucine, taurine, and creatine) previously developed from variable dose rate experiments was able to identify individuals with high sensitivity and specificity irrespective of radiation shielding. A panel of serum metabolites composed from previous untargeted studies on nonhuman primates had excellent performance for separating irradiated cohorts; however, a multi-omic approach to complement the metabolome could increase dose estimation confidence intervals. Overall, these results support the inclusion of small molecule markers in biodosimetry assays without substantial interference from upper or lower body shielding.
Institute
Georgetown University
Last NamePannkuk
First NameEvan
Address3970 Reservoir Rd, NW New Research Build, washington dc, District of Columbia, 20057, USA
Emailelp44@georgetown.edu
Phone2026875650
Submit Date2024-07-11
Analysis Type DetailLC-MS
Release Date2024-12-02
Release Version1
Evan Pannkuk Evan Pannkuk
https://dx.doi.org/10.21228/M8NR71
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002073
Project DOI:doi: 10.21228/M8NR71
Project Title:Impact of partial body shielding from very high dose rates on untargeted metabolomics in biodosimetry
Project Summary:A realistic exposure to ionizing radiation (IR) from an improvised nuclear device will likely include individuals that are partially shielded from the initial blast delivered at a very high-dose rate (VHDR). As different tissues have varying levels of radiosensitivity, e.g. hematopoietic vs. gastrointestinal tissues, the effects of shielding on radiation biomarkers needs to be addressed. Here, we explore how biofluid (urine and serum) metabolite signatures from male and female C57BL/6 mice exposed to VHDR (5 – 10 Gy/sec) total body irradiation (TBI, 0, 4, and 8 Gy) compare to individuals exposed to partial body irradiation (PBI) (lower body irradiated [LBI] or upper body irradiated [UBI] at an 8 Gy dose) using a data-independent acquisition untargeted metabolomics approach. Although sex differences were observed in the spatial groupings of urine signatures from TBI and PBI mice, a metabolite signature (N6,N6,N6-trimethyllysine, carnitine, propionylcarnitine, hexosamine-valine-isoleucine, taurine, and creatine) previously developed from variable dose rate experiments was able to identify individuals with high sensitivity and specificity irrespective of radiation shielding. A panel of serum metabolites composed from previous untargeted studies on nonhuman primates had excellent performance for separating irradiated cohorts; however, a multi-omic approach to complement the metabolome could increase dose estimation confidence intervals. Overall, these results support the inclusion of small molecule markers in biodosimetry assays without substantial interference from upper or lower body shielding.
Institute:Georgetown University
Last Name:Pannkuk
First Name:Evan
Address:3970 Reservoir Rd, NW New Research Build, washington dc, District of Columbia, 20057, USA
Email:elp44@georgetown.edu
Phone:2026875650

Subject:

Subject ID:SU003455
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Gender:Male and female
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id Sex Exposure Irradiation
SA362560POS_028F LB 8Gy
SA362561POS_083F LB 8Gy
SA362562POS_076F LB 8Gy
SA362563POS_071F LB 8Gy
SA362564POS_070F LB 8Gy
SA362565POS_068F LB 8Gy
SA362566POS_065F LB 8Gy
SA362567POS_063F LB 8Gy
SA362568POS_010F LB 8Gy
SA362569POS_009F LB 8Gy
SA362570POS_043F No exposure 0Gy
SA362571POS_106F No exposure 0Gy
SA362572POS_027F No exposure 0Gy
SA362573POS_022F No exposure 0Gy
SA362574POS_031F No exposure 0Gy
SA362575POS_080F No exposure 0Gy
SA362576POS_011F No exposure 0Gy
SA362577POS_040F No exposure 0Gy
SA362578POS_098F No exposure 0Gy
SA362579POS_013F No exposure 0Gy
SA362580POS_023F TB 4Gy
SA362581POS_012F TB 4Gy
SA362582POS_078F TB 4Gy
SA362583POS_017F TB 4Gy
SA362584POS_058F TB 4Gy
SA362585POS_049F TB 4Gy
SA362586POS_072F TB 4Gy
SA362587POS_097F TB 4Gy
SA362588POS_038F TB 4Gy
SA362589POS_037F TB 4Gy
SA362590POS_050F TB 8Gy
SA362591POS_052F TB 8Gy
SA362592POS_053F TB 8Gy
SA362593POS_091F TB 8Gy
SA362594POS_057F TB 8Gy
SA362595POS_036F TB 8Gy
SA362596POS_079F TB 8Gy
SA362597POS_029F TB 8Gy
SA362598POS_067F TB 8Gy
SA362599POS_094F TB 8Gy
SA362600POS_099F UB 8Gy
SA362601POS_082F UB 8Gy
SA362602POS_081F UB 8Gy
SA362603POS_103F UB 8Gy
SA362604POS_104F UB 8Gy
SA362605POS_056F UB 8Gy
SA362606POS_015F UB 8Gy
SA362607POS_042F UB 8Gy
SA362608POS_055F UB 8Gy
SA362609POS_051F UB 8Gy
SA362610POS_045M LB 8Gy
SA362611POS_026M LB 8Gy
SA362612POS_064M LB 8Gy
SA362613POS_096M LB 8Gy
SA362614POS_090M LB 8Gy
SA362615POS_085M No exposure 0Gy
SA362616POS_039M No exposure 0Gy
SA362617POS_066M No exposure 0Gy
SA362618POS_024M No exposure 0Gy
SA362619POS_077M No exposure 0Gy
SA362620POS_084M TB 4Gy
SA362621POS_054M TB 4Gy
SA362622POS_092M TB 4Gy
SA362623POS_044M TB 4Gy
SA362624POS_041M TB 4Gy
SA362625POS_069M TB 8Gy
SA362626POS_093M TB 8Gy
SA362627POS_105M TB 8Gy
SA362628POS_014M TB 8Gy
SA362629POS_095M UB 8Gy
SA362630POS_018M UB 8Gy
SA362631POS_016M UB 8Gy
SA362632POS_030M UB 8Gy
SA362633POS_025M UB 8Gy
Showing results 1 to 74 of 74

Collection:

Collection ID:CO003448
Collection Summary:Serum samples were prepared using BD Microtainer Tube (REF 365967) with ~100 µL of whole blood added to each tube, kept at room temperature for 30 min, then spun at 1300× g at 4 °C for 10 min. Serum was stored at −80 °C and then shipped on dry ice to Georgetown University Medical Center
Sample Type:Blood (serum)
Storage Conditions:-80℃

Treatment:

Treatment ID:TR003464
Treatment Summary:All animal experiments were approved by the Columbia University Institutional Animal Care and Use Committee (IACUC, protocol #AABA9603) and were conducted under all relevant federal and state guidelines. Male (n=5) and female (n=10) C57BL/6 mice (ages 12 – 14 weeks) were purchased from Charles River Laboratories (Frederick, MD) and randomly assigned to the zero-dose sham (0 Gy) and irradiated (4 and 8 Gy, total and partial body exposure) cohorts. Samples were collected at 1 day.

Sample Preparation:

Sampleprep ID:SP003462
Sampleprep Summary:A 5 μl aliquot of serum was mixed with 195 μl of cold 66% acetonitrile containing internal standards (2 μM debrisoquine [M+H]+ = 176.1188; 5 μM chlorpropamide [M+H]+ = 277.0414, [M-H]- = 275.0257; 30 μM 4-nitrobenzoic acid [M-H]- = 166.0141). The samples were vortexed and then incubated on ice for 10 min. Residual solids were pelleted to the bottom by centrifugation for 10 min (10,000 x g, 4°C), and then an aliquot was placed in a liquid chromatography (LC) vial.

Chromatography:

Chromatography ID:CH004148
Chromatography Summary:The LC and MS conditions for serum was as follows: LC solvent A (water/0.1% formic acid [FA]), solvent B (acetonitrile/0.1% FA), and solvent C (isopropanol/0.1% FA). Operating conditions for ESI were, capillary voltage 3 kV, cone voltage 30 V, desolvation temperature 500°C, desolvation gas flow 600 L/Hr. The gradient for serum was: 4 min 98% A 2% B, 4 min 40% A 60% B, 1.5 min 2% A 98% B, 2 min 11.8% B 88.2% C, 0.5 min 50% A 50% B, and 1 min 98% A 2% B at a flow rate of 0.5 ml/min, column temp 60 °C.
Instrument Name:Waters Acquity
Column Name:Waters ACQUITY UPLC BEH C18 (50 x 2.1mm,1.7um)
Column Temperature:60
Flow Gradient:4 min 98% A 2% B, 4 min 40% A 60% B, 1.5 min 2% A 98% B, 2 min 11.8% B 88.2% C, 0.5 min 50% A 50% B, and 1 min 98% A 2% B
Flow Rate:0.5 ml/min
Solvent A:100% water; 0.1% formic acid
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase
Solvent C:100% isopropanol; 0.1% formic acid

Analysis:

Analysis ID:AN005462
Analysis Type:MS
Chromatography ID:CH004148
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003334_AN005462_Results.txt
Units:peak area
  
Analysis ID:AN005463
Analysis Type:MS
Chromatography ID:CH004148
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003334_AN005463_Results.txt
Units:peak area
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