Shared diagnostic genes and potential mechanism between PCOS and recurrent implantation failure revealed by integrated transcriptomic analysis and machine learning

Abstract

Polycystic ovary syndrome (PCOS) is a complex endocrine metabolic disorder that affects 5–10% of women of reproductive age. The endometrium of women with PCOS has altered immune cells resulting in chronic low-grade inflammation, which attribute to recurrent implantation failure (RIF). In this study, we obtained three PCOS and RIF datasets respectively from the Gene Expression Omnibus (GEO) database. By analyzing differentially expressed genes (DEGs) and module genes using weighted gene co-expression networks (WGCNA), functional enrichment analysis, and three machine learning algorithms, we identified twelve diseases shared genes, and two diagnostic genes, including GLIPR1 and MAMLD1. PCOS and RIF validation datasets were assessed using the receiver operating characteristic (ROC) curve, and ideal area under the curve (AUC) values were obtained for each disease. Besides, we collected granulosa cells from healthy and PCOS infertile women, and endometrial tissues of healthy and RIF patients. RT-PCR was used to validate the reliability of GLIPR1 and MAMLD1. Furthermore, we performed gene set enrichment analysis (GSEA) and immune infiltration to explore the underlying mechanism of PCOS and RIF cooccurrence. Through the functional enrichment of twelve shared genes and two diagnostic genes, we found that both PCOS and RIF patients had disturbances in metabolites related to the TCA cycle, which eventually led to the massive activation of immune cells.

Causal relationship between systemic lupus erythematosus and primary liver cirrhosis based on two-sample bidirectional Mendelian randomization and transcriptome overlap analysis

“…Transcriptome overlap analysis is a genetic validation method for analyzing the relationship between two diseases. For example, based on three datasets of polycystic ovary syndrome and recurrent implantation failure, 12 disease overlapping genes were identified using weighted gene co expression networks, functional enrichment analysis, and three machine learning algorithms, which potential pathogenic associations and mechanisms between the two were explored [ 28 ]; The inflammatory immune pathway of calcified aortic valve disease (CAVD) related to chronic kidney disease (CKD) had been revealed, providing new insights for future serum based diagnosis and treatment interventions for CKD combined with CAVD [ 29 ]. In this study, 418 upregulated overlapping genes were identified using the GEO dataset of SLE and PBC, and their biological functions were found to be related to TNF signaling pathway and JAK-STAT signaling pathway, which was similar to previous reports [ 7 ].…”

Study of molecular patterns associated with ferroptosis in Parkinson’s disease and its immune signature

“…The essence of Gene Significance (GS) is the correlation between the genes within the module where it is located and the phenotype (our phenotype was selected as whether or not we had PD) [48]. Reviewing a large amount of literature, we found that, generally, a GS threshold between 0.2 and 0.5 is reasonable [53][54][55][56][57][58][59][60]. At the same time, we wanted to include as many genes as possible to see the relationship with ferroptosis, so for the GS threshold, we chose 0.2.…”