Dataset Information

Risk gene identification and support vector machine learning to construct an early diagnosis model of myocardial infarction.

ABSTRACT: The present study aimed to identify genes associated with increased risk of myocardial infarction (MI) and construct an early diagnosis model based on support vector machine (SVM) learning. The gene expression profile data of GSE34198, containing 97 human blood samples including 49 patients with MI and 48 healthy individuals, were obtained from the Gene Expression Omnibus database. Differentially expressed gene (DEG) screening, DEG enrichment analysis, protein?protein interaction (PPI) network investigation and clustering analysis were performed. The feature genes were identified using the neighboring score algorithm. Furthermore, a recursive feature elimination (RFE) algorithm was employed to screen risk factors among feature genes. The SVM prediction model was constructed and validated using the dataset GSE61144. A total of 1,207 DEGs (724 downregulated, 483 upregulated) between the two groups were identified. PPI analysis investigated 1,083 DEGs and 46,363 edges. In total, 87 genes were selected as candidate genes, and were primarily enriched in functions including 'G?protein coupled receptor signaling' or pathways such as 'focal adhesion'. Furthermore, 15 genes with a high RFE score were selected to construct an SVM prediction model. The model's average accuracy was 86%. Data set verification showed that the predictive precision reached 0.92. High expression of the genes vascular endothelial growth factor A, A?kinase anchoring protein 12 and olfactory receptor 8D2 were potential risk factors for MI. The SVM early diagnosis model constructed by candidate genes could not only predict early MI, but also provide risk probability according to the severity of MI.

SUBMITTER: Fang HZ

PROVIDER: S-EPMC7411293 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Risk gene identification and support vector machine learning to construct an early diagnosis model of myocardial infarction.

Fang Hong-Zhi HZ Hu Dan-Li DL Li Qin Q Tu Su S

Molecular medicine reports 20200617 3

The present study aimed to identify genes associated with increased risk of myocardial infarction (MI) and construct an early diagnosis model based on support vector machine (SVM) learning. The gene expression profile data of GSE34198, containing 97 human blood samples including 49 patients with MI and 48 healthy individuals, were obtained from the Gene Expression Omnibus database. Differentially expressed gene (DEG) screening, DEG enrichment analysis, protein‑protein interaction (PPI) network i ...[more]

PMID: 32705275

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Project description:The aim of the present study was to identify risk genes in myocardial infarction. Microarray data GSE34198, containing data from the peripheral blood of 49 myocardial infarction samples and 48 corresponding control samples, were downloaded from the Gene Expression Omnibus database to screen the differentially expressed genes (DEGs). The DEGs were used to construct a protein‑protein interaction (PPI) network of patient samples, from which the feature genes were identified using the neighboring score method. The recursive feature elimination (RFE) algorithm was employed to select the risk genes among feature genes, which were subsequently applied to perform a support vector machine (SVM) classifier to identify the specific signature in myocardial infarction samples. Another dataset, GSE61144, was also downloaded to verify the efficacy of the classifier. A total of 724 downregulated and 483 upregulated DEGs were screened in patient samples compared with control samples in the GSE34198 dataset. The PPI network of myocardial infarction was comprised of 1,083 nodes (genes) and 46,363 lines (connections). Using the neighborhood scoring method, the top 100 feature genes in myocardial infarction samples were identified as the disease feature genes, which distinguish the myocardial infarction samples from the control samples. The RFE algorithm screened 15 risk genes, which were employed to construct a SVM classifier with an average precision of 88% to the patient sample following visualization by a confusion matrix. The predictive precision of the classifier on another microarray dataset, GSE61144, was 0.92, with an average true positive of 0.9278 and an average false positive of 0.2361. A‑kinase‑anchoring protein 12 (AKAP12) and glycine receptor α2 (GLRA2) were two risk genes in the SVM classifier. Therefore, AKAP12 and GLRA2 exert potential roles in the development of myocardial infarction, potentially by influencing cardiac contractility and protecting against ischemia‑reperfusion injury, which may provide clues in developing potential diagnostic biomarkers or therapeutic targets for myocardial infarction.

Project description:ObjectiveThis study aimed to analyze immune-related genes and immune cell components in the peripheral blood of patients with acute myocardial infarction (AMI).MethodsSix datasets were obtained from the GEO repository comprising 88 healthy samples and 215 AMI samples. We performed the weighted gene co-expression analysis (WGCNA) and five machine learning (ML) methods to identify immune-related genes and construct diagnostic models. CIBERSORT algorithm was adopted for the assessment of the degree of immune infiltration. Finally, RT-PCR, immunofluorescence double and immunohistochemistry were conducted to analyze the expression level of the identification of featured immune-related genes and localization relationship in heart tissue of AMI mouse model.ResultsA total of 496 immune-related DEGs were obtained between AMI and normal samples. WGCNA finally determined the co-expression modules that showed the most significantly positively associated with AMI (r=0.41; P<0.001). Among the five ML models, XGBoost had the highest AUC (0.849) and accuracy (0.812) to discriminate patients with AMI from normal in the validation sets. Furthermore, we found that the proportion of chemokine receptor (CCR), macrophages, neutrophils, and Treg cells in the AMI groups was significantly higher than that in the normal groups. In vitro RT-PCR verification revealed that SOCS3, MMP9, and AQP9 expression increased significantly in the AMI mouse model. Among the 22 immune cells, AQP9, MMP9, and SOCS3 displayed the strongest positive correlation with neutrophils. In MI-mice, MPO stained strongly along the lateral cardiomyocytes, whereas it was weaker in sham mice. Combined immunofluorescence was observed in same parts of the cytoplasm of cardiomyocytes in myocardial infarction area, indicating co-localization of MPO with MMP9 and SOCS3 in these areas, respectively.ConclusionImmune-related genes and immune cells are intimately related to AMI. Constructing different ML models based on these biomarkers could be a valuable approach to diagnosing AMI in clinical practice.

Dataset Information

Risk gene identification and support vector machine learning to construct an early diagnosis model of myocardial infarction.

Publications

Risk gene identification and support vector machine learning to construct an early diagnosis model of myocardial infarction.

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