PXD035289

PXD035289 is an original dataset announced via ProteomeXchange.

Title	Temporal proteomics of human cerebrospinal fluid reveals novel differentially-regulated proteins after severe traumatic brain injury
Description	The pathophysiology of traumatic brain injury (TBI) requires further characterization to fully elucidate changes in molecular pathways. Cerebrospinal fluid (CSF) provides a rich repository of brain-associated proteins that may be affected by TBI. Here, we implemented high-resolution mass spectrometry to evaluate changes to the CSF proteome after severe TBI. 91 CSF samples were analyzed with mass spectrometry, collected from 16 patients with severe TBI (mean 32 yrs; 81% male) on day 0, 1, 2, 4, 7 and/or 10 post-injury (8-16 samples/timepoint) and compared to CSF obtained from 11 non-injured controls. We quantified 1152 proteins with mass spectrometry, of which approximately 80% were associated with CSF. 1083 proteins were differentially regulated after TBI compared to control samples. The most highly-upregulated proteins at each timepoint included neutrophil elastase, myeloperoxidase, cathepsin G, matrix metalloproteinase-8, and S100 calcium-binding proteins A8, A9 and A12—all proteins involved in neutrophil activation, recruitment, and degranulation. Pathway enrichment analysis confirmed the robust upregulation of proteins associated with innate immune responses. Conversely, downregulated pathways included those involved in nervous system development, and several proteins not previously identified after TBI such as testican-1 and latrophilin-1. We also identified 7 proteins (GM2A, Calsyntenin 1, FAT2, GANAB, Lumican, NPTX1, SFRP2) positively associated with an unfavorable outcome at 6 months post-injury. These findings highlight the robust innate immune response that occurs after severe TBI, supporting future studies to target neutrophil-related processes. In addition, the novel proteins we identified to be differentially regulated by severe TBI warrant further investigation as potential biomarkers or therapeutic targets.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:39:45.615.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ralf Schittenhelm
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-13 05:54:38	ID requested
1	2023-03-11 01:05:56	announced
⏵ 2	2023-11-14 08:39:46	announced	2023-11-14: Updated project metadata.

Shultz SR, Shah AD, Huang C, Dill LK, Schittenhelm RB, Morganti-Kossmann MC, Semple BD, Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury. J Neuroinflammation, 19(1):291(2022) [pubmed]

submitter keyword: cerebrospinal fluid, secondary injury, inflammation, TBI,proteins, biomarker

Bridgette Semple
contact affiliation	Monash University
contact email	Bridgette.Semple@monash.edu
lab head
Ralf Schittenhelm
contact affiliation	Monash University
contact email	ralf.schittenhelm@monash.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035289
     1. Label: PRIDE project
     2. Name: Temporal proteomics of human cerebrospinal fluid reveals novel differentially-regulated proteins after severe traumatic brain injury