Transcriptome analysis of HIV-infected peripheral blood monocytes: gene transcripts and networks associated with neurocognitive functioning
Title | Transcriptome analysis of HIV-infected peripheral blood monocytes: gene transcripts and networks associated with neurocognitive functioning |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Levine, AJ, Horvath, S, Miller, EN, Singer, EJ, Shapshak, P, Baldwin, GC, Martínez-Maza, O, Witt, MD, Langfelder, P |
Journal | Journal of Neuroimmunology |
Volume | 265 |
Issue | 1-2 |
Pagination | 96-105 |
Date Published | 12/2013 |
Keywords | External, Gene Expression, HIV-associated neurocognitive disorder, IL6R, Monocyte, transcriptome, WGCNA |
Abstract | Immunologic dysfunction, mediated via monocyte activity, has been implicated in the development of HIV-associated neurocognitive disorder (HAND). We hypothesized that transcriptome changes in peripheral blood monocytes relate to neurocognitive functioning in HIV+ individuals, and that such alterations could be useful as biomarkers of worsening HAND. METHODS: mRNA was isolated from the monocytes of 86 HIV+ adults and analyzed with the Illumina HT-12 v4 Expression BeadChip. Neurocognitive functioning, HAND diagnosis, and other clinical and virologic variables were determined. Data were analyzed using standard expression analysis and weighted gene co-expression network analysis (WGCNA). RESULTS: Neurocognitive functioning was correlated with multiple gene transcripts in the standard expression analysis. WGCNA identified two nominally significant co-expression modules associated with neurocognitive functioning, which were enriched with genes involved in mitotic processes and translational elongation. CONCLUSIONS: Multiple modified gene transcripts involved in inflammation, cytoprotection, and neurodegeneration were correlated with neurocognitive functioning. The associations were not strong enough to justify their use as biomarkers of HAND; however, the associations of two co-expression modules with neurocognitive functioning warrant further exploration. |
URL | http://www.ncbi.nlm.nih.gov/pubmed/24094461 |
DOI | 10.1016/j.jneuroim.2013.09.016 |