Dataset Information

Identification and validation of platelet-related diagnostic markers and potential drug screening in ischemic stroke by integrating comprehensive bioinformatics analysis and machine learning.

ABSTRACT:

Background

Ischemic stroke (IS), caused by blood and oxygen deprivation due to cerebral thrombosis, has links to activated and aggregated platelets. Discovering platelet-related biomarkers, developing diagnostic models, and screening antiplatelet drugs are crucial for IS diagnosis and treatment.

Methods and results

Combining and normalizing GSE16561 and GSE22255 datasets identified 1,753 upregulated and 1,187 downregulated genes. Fifty-one genes in the platelet-related module were isolated using weighted gene co-expression network analysis (WGCNA) and other analyses, including 50 upregulated and one downregulated gene. Subsequent enrichment and network analyses resulted in 25 platelet-associated genes and six diagnostic markers for a risk assessment model. This model's area under the ROC curve outperformed single genes, and in the peripheral blood of the high-risk group, immune infiltration indicated a higher proportion of CD4, resting CD4 memory, and activated CD4 memory T cells, along with a lower proportion of CD8 T cells in comparison to the low-risk group. Utilizing the gene expression matrix and the CMap database, we identified two potential drugs for IS. Finally, a rat MACO/R model was used to validate the diagnostic markers' expression and the drugs' predicted anticoagulant effects.

Conclusion

We identified six IS platelet-related biomarkers (APP, THBS1, F13A1, SRC, PPBP, and VCL) for a robust diagnostic model. The drugs alpha-linolenic acid and ciprofibrate have potential antiplatelet effects in IS. This study advances early IS diagnosis and treatment.

SUBMITTER: Geng Y

PROVIDER: S-EPMC10806171 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification and validation of platelet-related diagnostic markers and potential drug screening in ischemic stroke by integrating comprehensive bioinformatics analysis and machine learning.

Geng Yifei Y Liu Yuchen Y Wang Min M Dong Xi X Sun Xiao X Luo Yun Y Sun Xiaobo X

Frontiers in immunology 20240110

<h4>Background</h4>Ischemic stroke (IS), caused by blood and oxygen deprivation due to cerebral thrombosis, has links to activated and aggregated platelets. Discovering platelet-related biomarkers, developing diagnostic models, and screening antiplatelet drugs are crucial for IS diagnosis and treatment.<h4>Methods and results</h4>Combining and normalizing GSE16561 and GSE22255 datasets identified 1,753 upregulated and 1,187 downregulated genes. Fifty-one genes in the platelet-related module were ...[more]

PMID: 38268925

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Project description:BackgroundOsteoarthritis (OA) is a common cause of disability among the elderly, profoundly affecting quality of life. This study aims to leverage bioinformatics and machine learning to develop an artificial neural network (ANN) model for diagnosing OA, providing new avenues for early diagnosis and treatment.MethodsFrom the Gene Expression Omnibus (GEO) database, we first obtained OA synovial tissue microarray datasets. Differentially expressed genes (DEGs) associated with OA were identified through utilization of the Limma package and weighted gene co-expression network analysis (WGCNA). Subsequently, protein-protein interaction (PPI) network analysis and machine learning were employed to identify the most relevant potential feature genes of OA, and ANN diagnostic model and receiver operating characteristic (ROC) curve were constructed to evaluate the diagnostic performance of the model. In addition, the expression levels of the feature genes were verified using real-time quantitative polymerase chain reaction (qRT-PCR). Finally, immune cell infiltration analysis was performed using CIBERSORT algorithm to explore the correlation between feature genes and immune cells.ResultsThe Limma package and WGCNA identified a total of 72 DEGs related to OA, of which 12 were up-regulated and 60 were down-regulated. Then, the PPI network analysis identified 21 hub genes, and three machine learning algorithms finally screened four feature genes (BTG2, CALML4, DUSP5, and GADD45B). The ANN diagnostic model was constructed based on these four feature genes. The AUC of the training set was 0.942, and the AUC of the validation set was 0.850. In addition, the qRT-PCR validation results demonstrated a significant downregulation of BTG2, DUSP5, and GADD45 mRNA expression levels in OA samples compared to normal samples, while CALML4 mRNA expression level exhibited an upregulation. Immune cell infiltration analysis revealed B cells memory, T cells gamma delta, B cells naive, Plasma cells, T cells CD4 memory resting, and NK cells The abnormal infiltration of activated cells may be related to the progression of OA.ConclusionsBTG2, CALML4, DUSP5, and GADD45B were identified as potential feature genes for OA, and an ANN diagnostic model with good diagnostic performance was developed, providing a new perspective for the early diagnosis and personalized treatment of OA.

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Dataset Information

Identification and validation of platelet-related diagnostic markers and potential drug screening in ischemic stroke by integrating comprehensive bioinformatics analysis and machine learning.

Background

Methods and results

Conclusion

Publications

Identification and validation of platelet-related diagnostic markers and potential drug screening in ischemic stroke by integrating comprehensive bioinformatics analysis and machine learning.

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