Dataset Information

Lipid Droplet-Enriched Luminogens Enable Adoptive Macrophage Transfer for Treatment of Bacterial Sepsis

ABSTRACT: Lipid Droplet-Enriched Luminogens Enable Adoptive Macrophage Transfer for Treatment of Bacterial Sepsis

PROVIDER: PRJNA1223402 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32332614_1.fastq.gz	Fastqsanger.gz
	SRR32332614_2.fastq.gz	Fastqsanger.gz
	SRR32332615_1.fastq.gz	Fastqsanger.gz
	SRR32332615_2.fastq.gz	Fastqsanger.gz
	SRR32332616_1.fastq.gz	Fastqsanger.gz

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Project 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.

Dataset Information

Lipid Droplet-Enriched Luminogens Enable Adoptive Macrophage Transfer for Treatment of Bacterial Sepsis

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