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pmid:39229380
Identification of key metabolism-related genes and pathways in spontaneous preterm birth: combining bioinformatic analysis and machine learning.
Wenqi Lv · Han Xie · Shengyu Wu · Jiaqi Dong · Yuanhui Jia · Hao Ying
Frontiers in endocrinology · 2024 doi:10.3389/fendo.2024.1440436
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Complete file
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However, the etiology of sPTB remains poorly understood. Recent evidence has shown a strong association between metabolic disorders and sPTB. To determine the metabolic alterations in sPTB patients, we used various bioinformatics methods to analyze the abnormal changes in metabolic pathways in the preterm placenta via existing datasets.\nMethods: In this study, we integrated two datasets (GSE203507 and GSE174415) from the NCBI GEO database for the following analysis. We utilized the \"Deseq2\" R package and WGCNA for differentially expressed genes (DEGs) analysis; the identified DEGs were subsequently compared with metabolism-related genes. To identify the altered metabolism-related pathways and hub genes in sPTB patients, we performed multiple functional enrichment analysis and applied three machine learning algorithms, LASSO, SVM-RFE, and RF, with the hub genes that were verified by immunohistochemistry. Additionally, we conducted single-sample gene set enrichment analysis to assess immune infiltration in the placenta.\nResults: We identified 228 sPTB-related DEGs that were enriched in pathways such as arachidonic acid and glutathione metabolism. A total of 3 metabolism-related hub genes, namely, ANPEP, CKMT1B, and PLA2G4A, were identified and validated in external datasets and experiments. A nomogram model was developed and evaluated with 3 hub genes; the model could reliably distinguish sPTB patients and term labor patients with an area under the curve (AUC) > 0.75 for both the training and validation sets. Immune infiltration analysis revealed immune dysregulation in sPTB patients.\nConclusion: Three potential hub genes that influence the occurrence of sPTB through shadow participation in placental metabolism were identified; these results provide a new perspective for the development and targeting of treatments for sPTB.", "claims": [{"id": "claim-method", "statement": "Significantly differentially expressed genes (DEGs) were identified with the R package “DESeq2” under the criteria of p-adjustment < 0.05 and log2 | fold-change (FC) | >0.5.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39229380", "locator": "sections[5] \"Identification of differentially expressed genes with batch effect removal\" paragraph 2", "quote": "Significantly differentially expressed genes (DEGs) were identified with the R package “DESeq2” under the criteria of p-adjustment < 0.05 and log2 | fold-change (FC) | >0.5."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . 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