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pmid:36544902
Integrated analysis of WGCNA and machine learning identified diagnostic biomarkers in dilated cardiomyopathy with heart failure.
Yihao Zhu · Xiaojing Yang · Yao Zu
Frontiers in cell and developmental biology · 2022 doi:10.3389/fcell.2022.1089915
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Complete file
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In this study, three gene expression profiling datasets (GSE29819, GSE21610, GSE17800) and one single-cell RNA sequencing dataset (GSE95140) were obtained from the Gene Expression Omnibus (GEO) database. GSE29819 and GSE21610 were combined into the training group, while GSE17800 was the test group. We used the weighted gene co-expression network analysis (WGCNA) and identified fifteen driver genes highly associated with DCM with HF in the module. We performed the least absolute shrinkage and selection operator (LASSO) on the driver genes and then constructed five machine learning classifiers (random forest, gradient boosting machine, neural network, eXtreme gradient boosting, and support vector machine). Random forest was the best-performing classifier established on five Lasso-selected genes, which was utilized to select out NPPA, OMD, and PRELP for diagnosing DCM with HF. Moreover, we observed the up-regulation mRNA levels and robust diagnostic accuracies of NPPA, OMD, and PRELP in the training group and test group. Single-cell RNA-seq analysis further demonstrated their stable up-regulation expression patterns in various cardiomyocytes of DCM patients. Besides, through gene set enrichment analysis (GSEA), we found TGF-β signaling pathway, correlated with NPPA, OMD, and PRELP, was the underlying mechanism of DCM with HF. Overall, our study revealed NPPA, OMD, and PRELP serving as diagnostic biomarkers for DCM with HF, deepening the understanding of its pathogenesis.", "claims": [{"id": "claim-method", "statement": "Wilcoxon test was performed to analyze the differential expression of key genes in DCM with HF group versus control group.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36544902", "locator": "sections[12] \"Statistical analysis\" paragraph 2", "quote": "Wilcoxon test was performed to analyze the differential expression of key genes in DCM with HF group versus control group."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. 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"GSM3081658", "GSM3081659", "GSM3081660", "GSM3081661", "GSM3081662", "GSM3081663", "GSM3081664", "GSM3081665", "GSM3081666", "GSM3081667", "GSM3081668", "GSM3081669", "GSM3081670", "GSM3081671", "GSM3081672", "GSM3081673", "GSM3081674", "GSM3081675", "GSM3081676", "GSM3081677", "GSM3081678", "GSM3081679", "GSM3081680", "GSM3081681", "GSM3081682", "GSM3081683", "GSM3081684", "GSM3081685", "GSM3081686", "GSM3081687", "GSM3081688", "GSM3081689", "GSM3081690", "GSM3081691", "GSM3081692", "GSM3081693", "GSM3081694", "GSM3081695", "GSM3081696", "GSM3081697", "GSM3081698", "GSM3081699", "GSM3081700", "GSM3081701", "GSM3081702", "GSM3081703", "GSM3081704", "GSM3081705", "GSM3081706", "GSM3081707", "GSM3081708", "GSM3081709", "GSM3081710", "GSM3081711", "GSM3081712", "GSM3081713", "GSM3081714", "GSM3081715", "GSM3081716", "GSM3081717", "GSM3081718", "GSM3081719", "GSM3081720", "GSM3081721", "GSM3081722", "GSM3081723", "GSM3081724", "GSM3081725", "GSM3081726", "GSM3081727", "GSM3081728", "GSM3081729", "GSM3081730", "GSM3081731", "GSM3081732", "GSM3081733", "GSM3081734", "GSM3081735"], "sample_count": 1190, "group_sizes": null, "group_sizes_basis": null, "platform": "17021;16791", "taxon": "Homo sapiens; Mus musculus", "title": "Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure (RNA-Seq)", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE17800 not downloaded", "asset:data:geo:GSE17800 licence not read", "asset:data:geo:GSE21610 not downloaded", "asset:data:geo:GSE21610 licence not read", "asset:data:geo:GSE29819 not downloaded", "asset:data:geo:GSE29819 licence not read", "asset:data:geo:GSE95140 not downloaded", "asset:data:geo:GSE95140 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Wilcoxon test was performed to analyze the differential expression of key genes in DCM with HF group versus control group."}}, {"id": "method-2", "family": "machine_learning", "specific": "random_forest", "label": "Machine learning", "dsl_operations": [], "missing_operations": ["machine_learning_random_forest"], "expressible": false, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "random forest"}}, {"id": "method-3", "family": "machine_learning", "specific": "support_vector_machine", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, 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