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Large scale cerebrospinal fluid proteomics reveals biomarkers of Multiple Sclerosis

ABSTRACT: Cerebrospinal fluid (CSF) plays critical roles in clinical diagnostics, offers a window into neuropathological mechanisms and is available at scale. To enable its large-scale proteomics characterization, we developed a high-throughput mass spectrometry-based workflow based on the Orbitrap Astral. This workflow quantifies about 2100 proteins per sample at a throughput of 100 samples per day. We measured 2600 CSF samples across a discovery and replication cohort from patients with multiple sclerosis and related inflammatory CNS conditions as well as neurological controls. Analysis of CSF proteomes yielded a panel of 29 protein biomarkers to identify MS with better diagnostic performance than established clinical CSF markers (QIgG, QAlb, leukocyte count) amongst patients presenting with MS-like symptoms but without CSF-specific oligoclonal bands. To verify this biomarker panel and provide an assay format compatible with routine diagnostics, we have built a targeted assay on the Stellar mass spectrometer. With this assay, we have remeasured the discovery and replication cohort, confirming the diagnostic performance. This repository entry pertains to the targeted assay data only, the discovery proteomics data is deposited separately, see methods section of the publication.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD064513 | Pride | 2025-12-10

REPOSITORIES: Pride

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			Action	DRS
	DIA_library_for_targeting_analysis.zip	Other
	PL01_Stellar.zip	Other
	PL02_Stellar.zip	Other
	PL03_Stellar.zip	Other
	PL04_Stellar.zip	Other

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