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A novel method for characterizing cell-cell interactions at single-cell resolution reveals unique signatures in blood T cell-monocyte complexes during infection

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE273019 | GEO | 2024/11/06

REPOSITORIES: GEO

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Project description:BackgroundOvarian cancer (OC) is a common tumor of the female reproductive system, while Alzheimer's disease (AD) is a prevalent neurodegenerative disease that primarily affects cognitive function in the elderly. Monocytes are immune cells in the blood that can enter tissues and transform into macrophages, thus participating in immune and inflammatory responses. Overall, monocytes may play an important role in Alzheimer's disease and ovarian cancer.MethodsThe CIBERSORT algorithm results indicate a potential crucial role of monocytes/macrophages in OC and AD. To identify monocyte marker genes, single-cell RNA-seq data of peripheral blood mononuclear cells (PBMCs) from OC and AD patients were analyzed. Enrichment analysis of various cell subpopulations was performed using the "irGSEA" R package. The estimation of cell cycle was conducted with the "tricycle" R package, and intercellular communication networks were analyzed using "CellChat". For 134 monocyte-associated genes (MRGs), bulk RNA-seq data from two diseased tissues were obtained. Cox regression analysis was employed to develop risk models, categorizing patients into high-risk (HR) and low-risk (LR) groups. The model's accuracy was validated using an external GEO cohort. The different risk groups were evaluated in terms of immune cell infiltration, mutational status, signaling pathways, immune checkpoint expression, and immunotherapy. To identify characteristic MRGs in AD, two machine learning algorithms, namely random forest and support vector machine (SVM), were utilized.ResultsBased on Cox regression analysis, a risk model consisting of seven genes was developed in OC, indicating a better prognosis for patients in the LR group. The LR group had a higher tumor mutation burden, immune cell infiltration abundance, and immune checkpoint expression. The results of the TIDE algorithm and the IMvigor210 cohort showed that the LR group was more likely to benefit from immunotherapy. Finally, ZFP36L1 and AP1S2 were identified as characteristic MRGs affecting OC and AD progression.ConclusionThe risk profile containing seven genes identified in this study may help further guide clinical management and targeted therapy for OC. ZFP36L1 and AP1S2 may serve as biomarkers and new therapeutic targets for patients with OC and AD.

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A novel method for characterizing cell-cell interactions at single-cell resolution reveals unique signatures in blood T cell-monocyte complexes during infection

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