Background: HIV Associated Neurological Disorders (HAND) is relatively common among people with HIV-1 infection, even those taking combined antiretroviral treatment (cART). Genome-wide screening of transcription regulation in brain tissue helps in identifying substantial abnormalities present in patients’ gene transcripts and to discover possible biomarkers for HAND. This study explores the possibility of identifying differentially expressed (DE) genes, which can serve as potential biomarkers to detect HAND. In this study, we have investigated the gene expression levels of three subject groups with different impairment levels of HAND along with a control group in three distinct brain sectors: white matter, frontal cortex, and basal ganglia.
Methods: Linear models with weighted least squares along with Benjamini-Hochberg multiple corrections were used to identify DE genes in each brain region. Genes with an adjusted p-value of less than 0.01 were identified as differentially expressed. Principal component analyses (PCA) were performed to detect any groupings among the subject groups. Significance Analysis of Microarrays (SAM) and random forests (RF) methods with two distinct approaches were used to identify DE genes.
Results: A total of 710 genes in basal ganglia, 794 genes in the frontal cortex, and 1481 genes in white matter were screened. The highest proportion of DE genes was observed within the two brain regions, frontal neocortex, and basal ganglia. PCA analyses do not exhibit clear groupings among four subject groups. SAM and RF models reveal the genes, CIRBP, RBM3, GPNMB, ISG15, IFIT6, IFI6, and IFIT3, to have DE genes in the frontal cortex or basal ganglia among the subject groups. The gene, GADD45A, a protein-coding gene whose transcript levels tend to increase with stressful growth arrest conditions, was consistently ranked among the top genes by both RF models within the frontal cortex.
Conclusions: Our study contributes to a comprehensive understanding of the gene expression levels of the subject with different severity levels of HAND. Several genes that appear to play critical roles in the inflammatory response have been found, and they have an excellent potential to be used as biomarkers to detect HAND under further investigations.
Hansapani Rodrigo, Bryan Martinez, Roberto De La Garza et al. HIV-Associated Neurocognitive Disorder (HAND) Biomarker Identification: Significance Analysis of Microarrays and Two Persuasive Approaches with Random Forest, 26 March 2020, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-19489/v1]
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