PXD064125

PXD064125 is an original dataset announced via ProteomeXchange.

Title	Plasma proteomics identifies molecular subtypes in sepsis
Description	Background The heterogeneity of sepsis represents a major problem for the development of personalized sepsis therapies. Thus, sepsis subtyping emerged as an important tool to approach this problem, but little progress was made due to insufficient molecular insights. Modern proteomics techniques allow the identification of subtypes and enable molecular and mechanistical insights. Here, we analyzed a prospective multi-center sepsis cohort using plasma proteomics to describe and characterize sepsis plasma proteome subtypes. Methods Plasma samples from 333 patients collected at days 1 and 4 of sepsis were analyzed using liquid-chromatography coupled to tandem mass spectrometry. Plasma proteome subtypes were identified using K-means clustering and were characterized based on clinical routine data, cytokine measurements and proteomics data. A random forest machine learning (ML) classifier was generated to enable the assignment of patients to the subtypes in future. Results Four subtypes with different sepsis severity were identified. Cluster 0 represented the most severe sepsis with 100 % mortality. Cluster 1, 2 and 3 showed a gradual decrease of the median SOFA score, which was reflected by clinical data and cytokine measurements. On the proteome level, the subtypes were characterized by distinct molecular features. We found an alternating immune response with cluster 1 showing prominent activation of the adaptive immune system as indicated by elevated levels of immunoglobulins (Ig) that were verified using orthogonal measurements. Cluster 2 was characterized by acute inflammation and the lowest Ig levels. Cluster 3 represented the sepsis proteome baseline of the investigated cohort. We generated a ML classifier and optimized it for a minimum number of proteins that could realistically be implemented into routine diagnostics. The final model was based on 10 proteins and Ig quantities and allowed the assignment of patients to clusters 1, 2 and 3 with high confidence. Conclusion The identified plasma proteome subtypes provide insights into immune response and disease mechanisms and allow conclusions on appropriate therapeutic measures. Thus, they represent a step forward in the development of targeted therapies and personalized medicine in sepsis.
HostingRepository	PRIDE
AnnounceDate	2025-09-05
AnnouncementXML	Submission_2025-09-05_00:16:50.303.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thilo Bracht
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-20 15:57:50	ID requested
⏵ 1	2025-09-05 00:16:52	announced

Bracht T, Kappler K, Bayer M, Grell F, Schork K, Palmowski L, Koos B, Rahmel T, Ziehe D, Unterberg M, Bergmann L, Rump K, Broecker-Preuss M, Limper U, Henzler D, Ehrentraut SF, von Groote T, Zarbock A, Pfaender S, Babel N, Marcus-Alic K, Eisenacher M, Adamzik M, Sitek B, Nowak H, Plasma proteomics identifies molecular subtypes in sepsis. Crit Care, 29(1):392(2025) [pubmed]

10.1186/s13054-025-05639-6;

submitter keyword: Machine Learning, Precision Medicine, Subclasses, Plasma, Hierarchical Clustering,Sepsis, Clinical Routine Data

Thilo Bracht
contact affiliation	Medizinisches Proteom-Center, Ruhr University Bochum Clinic for Anesthesiology, Intensive Care and Pain Therapy, Knappschaft Clinics University Hospital Bochum
contact email	thilo.bracht@rub.de
lab head
Thilo Bracht
contact affiliation	Clinical Proteomics
contact email	thilo.bracht@rub.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/09/PXD064125

PRIDE project URI

• PRIDE
  1. PXD064125
     1. Label: PRIDE project
     2. Name: Plasma proteomics identifies molecular subtypes in sepsis