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Series GSE252430 Query DataSets for GSE252430
Status Public on Jan 03, 2024
Title Comparison of Proteomic Expression Profiles after Radiation Exposure across Four Different Species
Platform organism Homo sapiens
Sample organisms Macaca mulatta; Homo sapiens; Sus scrofa; Mus musculus
Experiment type Other
Summary There is a need to identify biomarkers of radiation exposure for use in development of circulating biodosimeters for radiation exposure and for clinical use as markers of radiation injury. Most research approaches for biomarker discovery rely on a single animal model. The current study sought to take advantage of a novel aptamer-based proteomic assay which has been validated for use in many species to characterize changes to the blood proteome after total-body irradiation (TBI) across four different mammalian species including humans. Plasma was collected from C57BL6 mice, Sinclair minipigs, and Rhesus non-human primates (NHPs) receiving a single dose of TBI at a range of 3.3 Gy to 4.22 Gy at 24 h postirradiation. NHP and minipig models were irradiated using a 60Co source at a dose rate of 0.6 Gy/min, the C57BL6 mouse model using an X-ray source at a dose rate of 2.28 Gy/min and clinical samples from a photon source at 10 cGy/min. Plasma was collected from human patients receiving a single dose of 2 Gy TBI collected 6 h postirradiation. Plasma was screened using the aptamer-based SomaLogic SomaScan® proteomic assay technology to evaluate changes in the expression of 1,310 protein analytes. Confirmatory analysis of protein expression of biomarker HIST1H1C, was completed using plasma from C57BL6 mice receiving a 2, 3.5 or 8 Gy TBI collected at days 1, 3, and 7 postirradiation by singleplex ELISA. Summary of key pathways with altered expression after radiation exposure across all four mammalian species was determined using Ingenuity Pathway Analysis (IPA). Detectable values were obtained for all 1,310 proteins in all samples included in the SomaScan assay. A subset panel of protein biomarkers which demonstrated significant (p < 0.05) changes in expression of at least 1.3-fold after radiation exposure were characterized for each species. IPA of significantly altered proteins yielded a variety of top disease and biofunction pathways across species with the organismal injury and abnormalities pathway held in common for all four species. The HIST1H1C protein was shown to be radiation responsive within the human, NHP and murine species within the SomaScan dataset and was shown to demonstrate dose dependent upregulation at 2, 3.5 and 8 Gy at 24 h postirradiation in a separate murine cohort by ELISA. The SomaScan proteomics platform is a useful screening tool to evaluate changes in biomarker expression across multiple mammalian species. In our study, we were able to identify a novel biomarker of radiation exposure, HIST1H1C, and characterize panels of radiation responsive proteins and functional proteomic pathways altered by radiation exposure across murine, minipig, NHP and human species. Our study demonstrates the efficacy of using a multispecies approach for biomarker discovery.
 
Overall design For this study Rhesus monkeys (Macaca mulatta) between 5–8 years of age received a single dose of TBI between 3.85 and 4.22 Gy. Plasma samples were collected at 24 h postirradiation using venipuncture collection. Pre- and postirradiation samples were matched for each individual animal. Animal care was conducted according to the Standard Operating Procedures of CiToxLAB North America under Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) standards.
Web link https://pubmed.ncbi.nlm.nih.gov/35073400/
 
Contributor(s) Sproull M
Citation(s) 35073400
Submission date Jan 03, 2024
Last update date Jan 03, 2024
Contact name Uma T Shankavaram
E-mail(s) uma@mail.nih.gov
Phone 301-496-6718
Organization name NIH
Department NCI
Lab Radiation Oncology Branch
Street address 9000 Rockville Pike
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL33741 SomaScan version 1.3k
Samples (26)
GSM8001279 SAMPLE 1 control NHP
GSM8001280 SAMPLE 2 Day1postIR NHP
GSM8001281 SAMPLE 3 control NHP
Relations
BioProject PRJNA1060639

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE252430_data.txt.gz 132.0 Kb (ftp)(http) TXT
GSE252430_multisp.DiffExp.xlsx 549.6 Kb (ftp)(http) XLSX

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