Identification of key immune regulatory genes in HIV-1 progression

Gene. 2021 Aug 5:792:145735. doi: 10.1016/j.gene.2021.145735. Epub 2021 May 26.

Abstract

Human immunodeficiency virus (HIV) infection causes acquired immunodeficiency syndrome (AIDS), one of the most devastating diseases affecting humankind. Here, we have proposed a framework to examine the differences among microarray gene expression data of uninfected and three different HIV-1 infection stages using module preservation statistics. We leverage the advantage of gene co-expression networks (GCN) constructed for each infection stages to detect the topological and structural changes of a group of differentially expressed genes. We examine the relationship among a set of co-expression modules by constructing a module eigengene network considering the overall similarity/dissimilarity among the genes within the modules. We have utilized different module preservation statistics with two composite statistics: "Zsummary" and "MedianRank" to examine the changes in co-expression patterns between modules. We have found several interesting results on the preservation characteristics of gene modules across different stages. Some genes are identified to be preserved in a pair of stages while altering their characteristics across other stages. We further validated the obtained results using permutation test and classification techniques. The biological significances of the obtained modules have also been examined using gene ontology and pathway-based analysis. Additionally, we have identified a set of key immune regulatory hub genes in the associated protein-protein interaction networks (PPINs) of the differentially expressed (DE) genes, which interacts with HIV-1 proteins and are likely to act as potential biomarkers in HIV-1 progression.

Keywords: Clustering; Gene co-expression network; HIV-1 and human protein interactions; HIV-1 progression; Immune regulatory genes; Module eigengene; Module preservation.

MeSH terms

  • Acute Disease
  • Antigens, CD / classification
  • Antigens, CD / genetics*
  • Antigens, CD / immunology
  • Chemokines / classification
  • Chemokines / genetics*
  • Chemokines / immunology
  • Chronic Disease
  • Datasets as Topic
  • Disease Progression
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Gene Regulatory Networks
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / growth & development
  • HIV-1 / pathogenicity*
  • Host-Pathogen Interactions / genetics*
  • Host-Pathogen Interactions / immunology
  • Human Immunodeficiency Virus Proteins / classification
  • Human Immunodeficiency Virus Proteins / genetics*
  • Human Immunodeficiency Virus Proteins / immunology
  • Humans
  • Microarray Analysis
  • Molecular Sequence Annotation
  • Protein Binding
  • Signal Transduction

Substances

  • Antigens, CD
  • Chemokines
  • Human Immunodeficiency Virus Proteins