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Comprehensive analysis of femoral head necrosis based on machine learning and bioinformatics analysis
Zheng Chen1, Yuankang Jiang1, Suwen Wu1
1Guangzhou University of Chinese Medicine Third Clinical Medical College, Guangzhou, China.
Abstract:
Osteonecrosis of the femoral head (ONFH) is a kind of disabling disease, given that the molecular mechanism of ONFH has not been elucidated, it is of significance to use bioinformatics analysis to understand the disease mechanism of ONFH and discover biomarkers. Gene set for ONFH GSE74089 was downloaded in the Gene Expression Omnibus, and "limma" package in R software was used to identify differentially expressed genes related to oxidative stress. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyze were performed for functional analysis. We constructed a protein interaction network and identified potential transcription factors and therapeutic drugs for the hub genes, and delineated the TF-hub genes network. Least absolute shrinkage and selection operator regression, support vector machine and cytoHubba were used to screen feature genes and key genes, which were validated by Receiver operating characteristic. CIBERSORT was used to explored the immune microenvironment. Subsequently, we identified the function of key genes using Gene set variation analysis and their relationship with each type of immune cell. Finally, molecular docking validated the binding association between molecules and validated genes. We detected 144 differentially expressed oxidative stress-related genes, and enrichment analysis showed that they were enriched in reactive oxygen species and AGE-RAGE signaling pathway. Protein-protein interaction and TF-hub genes network were conducted. Further exploration suggested that APOD and TMEM161A were feature genes, while TNF, NOS3 and CASP3 were key genes. Receiver operating characteristic analysis showed that APOD, CASP3, NOS3, and TNF have strong diagnostic ability. The key genes were enriched in oxidative phosphorylation. CIBERSORT analysis showed that 17 types immune cells were differentially relocated, and most of which were also closely related to key genes. In addition, genistein maybe potential therapeutic compound. In all, we identified that TNF, NOS3, and CASP3 played key roles on ONFH, and APOD, CASP3, NOS3, and TNF could serve as diagnostic biomarkers.
Insights
This study identifies key genes (TNF, NOS3, CASP3) and diagnostic biomarkers (APOD, CASP3, NOS3, TNF) for osteonecrosis of the femoral head (ONFH) using bioinformatics analysis of oxidative stress pathways.
Area of Science:
- Genomics and Bioinformatics
- Molecular Biology
- Immunology
Background:
- Osteonecrosis of the femoral head (ONFH) is a debilitating condition with an unclear molecular mechanism.
- Understanding ONFH pathogenesis is crucial for identifying diagnostic biomarkers and therapeutic targets.
- Bioinformatics approaches offer a powerful tool to elucidate complex disease mechanisms.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying ONFH using bioinformatics analysis.
- To identify differentially expressed genes related to oxidative stress in ONFH.
- To discover potential diagnostic biomarkers and therapeutic targets for ONFH.
Main Methods:
- Downloaded ONFH gene expression data (GSE74089) from Gene Expression Omnibus.
- Utilized R software ('limma' package) for differential gene expression analysis.
- Performed Gene Ontology, KEGG pathway enrichment, protein-protein interaction network construction, LASSO, SVM, cytoHubba, CIBERSORT, GSVA, and molecular docking.
Main Results:
- Identified 144 differentially expressed oxidative stress-related genes, enriched in reactive oxygen species and AGE-RAGE signaling.
- Discovered APOD and TMEM161A as feature genes, and TNF, NOS3, and CASP3 as key genes.
- Validated APOD, CASP3, NOS3, and TNF as potential diagnostic biomarkers with strong diagnostic ability; identified genistein as a potential therapeutic compound.
Conclusions:
- TNF, NOS3, and CASP3 play critical roles in the pathogenesis of ONFH.
- APOD, CASP3, NOS3, and TNF demonstrate significant potential as diagnostic biomarkers for ONFH.
- Bioinformatics analysis provides valuable insights into ONFH mechanisms and biomarker discovery.
