Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies

Bioengineered. 2021 Dec;12(1):2214-2227. doi: 10.1080/21655979.2021.1933743.

Abstract

This study aims to explore biomarkers associated with vitiligo and analyze the pathological role of immune cell infiltration in the disease. We used the robust rank aggregation (RRA) method to integrate three vitiligo data sets downloaded from gene expression omnibus database, identify the differentially expressed genes (DEGs) and analyze the functional correlation. Then, the comprehensive strategy of combined weighted gene coexpression network analysis (WGCNA) and logical regression of the selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF) machine learning algorithm are employed to screen and biomarkers associated with vitiligo. Finally, the immune cell infiltration of vitiligo was evaluated by CIBERSORT, and the correlation between biomarkers and infiltrating immune cells was analyzed. Herein, we identified 131 robust DEGs, and enrichment analysis results showed that robust DEGs and melanogenesis were closely associated with vitiligo development and progression. TYR, TYRP1, DCT and LARP7 were identified as vitiligo-related biomarkers. Immune infiltration analysis demonstrated that CD4 T Cell, CD8 T Cell, Tregs, NK cells, dendritic cells, and macrophages were involved in vitiligo's pathogenesis. In summary, we adopted a comprehensive strategy to screen biomarkers related to vitiligo and explore the critical role of immune cell infiltration in vitiligo.Abbreviations: TYR, Tyrosinase; TYRP1, Tyrosinase-related protein-1; DCT, dopachrome tautomerase; LARP7, La ribonucleoprotein domain family, member-7; RRA, robust rank aggregation; DEGs, differentially expressed genes; WGCNA, weighted gene coexpression network analysis; LASSO, logical regression of the selection operator; SVM-RFE, support vector machine recursive feature elimination; RF, random forest; GWAS, Genome-wide association study; FasL, Fas-Fas ligand; Tregs, T-regulatory cells; NK, natural killer; GEPCs, gene expression profiling chips; GO, gene ontology; GSEA, gene set enrichment analysis; FDR, false discovery rate; AUC, area under the curve; ROC, receiver-operating characteristic; BP, biological process; CC, cellular component; MF, molecular function.

Keywords: Vitiligo; biomarkers; cibersort; immune cells; machine learning algorithm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Databases, Genetic
  • Genetic Markers / genetics
  • Humans
  • Intramolecular Oxidoreductases / genetics*
  • Intramolecular Oxidoreductases / metabolism
  • Lymphocytes / immunology
  • Machine Learning
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Monophenol Monooxygenase / genetics*
  • Monophenol Monooxygenase / metabolism
  • Oxidoreductases / genetics*
  • Oxidoreductases / metabolism
  • Ribonucleoproteins / genetics*
  • Ribonucleoproteins / metabolism
  • Transcriptome / genetics
  • Vitiligo* / enzymology
  • Vitiligo* / genetics
  • Vitiligo* / immunology

Substances

  • Genetic Markers
  • Larp7 protein, human
  • Membrane Glycoproteins
  • Ribonucleoproteins
  • Oxidoreductases
  • TYRP1 protein, human
  • Monophenol Monooxygenase
  • Intramolecular Oxidoreductases
  • dopachrome isomerase

Grants and funding

This project was supported by grants from the National Natural Science Foundation of China (No. 81860550).