Integrating Transcriptome-Wide Association Study and mRNA Expression Profiling Identifies Novel Genes Associated With Osteonecrosis of the Femoral Head

Ma, Mei; Li, Peilin; Liu, Li; Cheng, Shiqiang; Cheng, Bolun; Liang, Chu Jun; Tan, Shengshun; Li, Wenyu; Wen, Yan; Guo, Xiong; Wu, Cuiyan

doi:10.3389/fgene.2021.663080

Cited by 3 publications

(2 citation statements)

References 44 publications

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“…Briefly, the British Biobank gene data set contains the genome-wide genotype data of 452264 participants, including 1265 AS patients. DNA was extracted from stored blood samples of individuals, and genotyped using the UK Biobank Axiom array ( 13 ). There are 62,394 genotype variants that have passed quality control through the Applied Biosystems British Biobank Axiom Array.…”

Section: Methodsmentioning

confidence: 99%

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Transcriptome-Wide Association Studies and Integration Analysis of mRNA Expression Profiles Identify Candidate Genes and Pathways Associated With Ankylosing Spondylitis

Feng

Liu

et al. 2022

Front. Immunol.

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This study aimed to identify susceptibility genes and pathways associated with ankylosing spondylitis (AS) by integrating whole transcriptome-wide association study (TWAS) analysis and mRNA expression profiling data. AS genome-wide association study (GWAS) summary data from the large GWAS database were used. This included data of 1265 AS patients and 452264 controls. A TWAS of AS was conducted using these data. The analysis software used was FUSION, and Epstein-Barr virus–transformed lymphocytes, transformed fibroblasts, peripheral blood, and whole blood were used as gene expression references. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the important genes identified via TWAS. Protein-protein interaction (PPI) network analysis based on the STRING database was also performed to detect genes shared by TWAS and mRNA expression profiles in AS. TWAS identified 920 genes (P <0.05) and analyzed mRNA expression profiles to obtain 1183 differential genes. Following comparison of the TWAS results and mRNA expression characteristics, we obtained 70 overlapping genes and performed GO and KEGG enrichment analyses of these genes to obtain 16 pathways. Via PPI network analysis, we obtained the protein interaction network and performed MCODE analysis to acquire the HUB genes. Similarly, we performed GO and KEGG analyses on the genes identified by TWAS, obtained 98 pathways after screening, and analyzed protein interactions via the PPI network. Through the integration of TWAS and mRNA expression analysis, genes related to AS and GO and KEGG terms were determined, providing new evidence and revealing the pathogenesis of AS. Our AS TWAS work identified novel genes associated with AS, as well as suggested potential tissues and pathways of action for these TWAS AS genes, providing a new direction for research into the pathogenesis of AS.

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Section: Methodsmentioning

confidence: 99%

“…There are 62,394 genotype variants that have passed quality control through the Applied Biosystems British Biobank Axiom Array. This data set contains 9,113,133 calculation variants after filtering ( 13 ). The IMPUTE4 program is used to perform responsibilities ( ).…”

Section: Methodsmentioning

confidence: 99%

Transcriptome-Wide Association Studies and Integration Analysis of mRNA Expression Profiles Identify Candidate Genes and Pathways Associated With Ankylosing Spondylitis

Feng

Liu

et al. 2022

Front. Immunol.

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Integrated Analysis of miRNA-mRNA Regulatory Networks Associated with Osteonecrosis of the Femoral Head

Yu¹,

Yao

Jiang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Osteonecrosis of the femoral head (ONFH) accounts for as many as 18% of total hip arthroplasties. Knowledge of genetic changes and molecular abnormalities could help identify individuals considered to be at a higher risk of developing ONFH. In this study, we sought to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) associated with ONFH by integrated bioinformatics analyses as well as to construct the miRNA-mRNA regulatory network involving in the pathogenesis of ONFH. We performed differential expression analysis using a gene expression profile GSE123568 and a miRNA expression profile GSE89587 deposited in the Gene Expression Omnibus and identified 47 DEmiRs (24 upregulated miRNAs and 23 downregulated miRNAs) and 529 DEGs (218 upregulated genes and 311 downregulated genes). Gene Ontology enrichment analyses of DEGs suggested that DEGs were significantly enriched in neutrophil activation, cytosol, and ubiquitin-protein transferase activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs revealed that DEGs were significantly enriched in transcriptional misregulation in cancer. DEGs-based miRNA-mRNA regulatory networks were obtained by searching miRNA-mRNA prediction databases, TargetScan, miTarBase, miRMap, miRDB, and miRanda databases. Then, overlapped miRNAs were selected between these putative miRNAs and DEmiRs between ONFH and non-ONFH, and pairs of the DEmiR-DEG regulatory network were finally depicted. There were 12 nodes and 64 interactions for upDEmiR-downDEG regulatory networks and 6 nodes and 16 interactions for downDEmiR-upDEG regulatory networks. Using the STRING database, we established a protein-protein interaction network based on the overlapped DEGs between ONFH and non-ONFH. C5AR1, CDC27, CDC34, KAT2B, CPPED1, TFDP1, and MX2 were identified as the hub genes. The present study characterizes the miRNA profile, gene profile, and miRNA-mRNA regulatory network in ONFH, which may contribute to the interpretation of the pathogenesis of ONFH and the identification of novel biomarkers and therapeutic targets for ONFH.

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Differentially Expressed Genes Reveal the Biomarkers and Molecular Mechanism of Osteonecrosis

Zhang

Shi

2022

Journal of Healthcare Engineering

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Osteonecrosis is one of the most refractory orthopedic diseases, which seriously threatens the health of old patients. High-throughput sequencing (HTS) and microarray analysis have confirmed as an effective way for investigating the pathological mechanism of disease. In this study, GSE7716, GSE74089, and GSE123568 were obtained from Gene Expression Omnibus (GEO) database and used to identify differentially expressed genes (DEGs) by R language. Subsequently, the DEGs were analyzed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Moreover, the protein-protein interaction (PPI) network of DEGs was analyzed by STRING database and Cytoscape. The results showed that 318 downregulated genes and 58 upregulated genes were observed in GSE7116; 690 downregulated genes and 1148 upregulated genes were screened from 34183 genes in GSE74089. The DEGs involved in progression of osteonecrosis involved inflammation, immunological rejection, and bacterial infection-related pathways. The GO enrichment showed that osteonecrosis was related with extracellular matrix, external encapsulating structure organization, skeletal system development, immune response activity, cell apoptosis, mononuclear cell differentiation, and serine/threonine kinase activity. Moreover, PPI network showed that the progression of osteonecrosis of the femoral head was related with CCND1, CDH1, ESR1, SPP1, LOX, JUN, ITGA, ABL1, and VEGF, and osteonecrosis of the jaw is related with ACTB, CXCR4, PTPRC, IL1B, CXCL8, TNF, JUN, PTGS2, FOS, and RHOA. In conclusion, this study identified the hub factors and pathways which might play important roles in progression of osteonecrosis and could be used as potential biomarkers for diagnosis and treatment of osteonecrosis.

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Integrating Transcriptome-Wide Association Study and mRNA Expression Profiling Identifies Novel Genes Associated With Osteonecrosis of the Femoral Head

Cited by 3 publications

References 44 publications

Transcriptome-Wide Association Studies and Integration Analysis of mRNA Expression Profiles Identify Candidate Genes and Pathways Associated With Ankylosing Spondylitis

Transcriptome-Wide Association Studies and Integration Analysis of mRNA Expression Profiles Identify Candidate Genes and Pathways Associated With Ankylosing Spondylitis

Integrated Analysis of miRNA-mRNA Regulatory Networks Associated with Osteonecrosis of the Femoral Head

Differentially Expressed Genes Reveal the Biomarkers and Molecular Mechanism of Osteonecrosis

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