Functional genomic relationships in HIV-1 disease revealed by gene-expression profiling of primary human peripheral blood mononuclear cells
Functional genomic relationships in HIV-1 disease revealed by gene-expression profiling of primary human peripheral blood mononuclear cells
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DOI：
10.1086/430321
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发表时间：
2005-06-15
影响因子：
6.4
通讯作者：
Vahey, MT
中科院分区：
文献类型：
--
作者：
Ockenhouse, CF;Bernstein, WB;Vahey, MT
背景。通过分析人外周血单核细胞基因表达谱来评估生物标志物，以了解与体内人类免疫缺陷病毒 1 型 (HIV-1) 感染相关的转录变化。方法。监督学习算法被用来创建特征基因集，可用于区分血清阳性和血清阴性样本，并描绘感染早期阶段疾病状态的变化。生物信息学工具用于对人进行分类，并对差异表达基因组进行功能表征，以阐明病毒感染对宿主细胞基因表达模式的影响。结果。确定了可用于准确确定 HIV-1 血清状态的 10 个基因特征集。使用 6 基因特征集来区分 CD4(+) T 细胞计数表现出差异变化的血清反应阳性者，准确度为 93%。 HIV-1差异表达基因的功能分类表明，下调基因的优势与免疫反应和细胞凋亡相关。与CD4+ T细胞计数减少的人相比，CD4+ T细胞计数增加的人的层次聚类分析的特点是与细胞凋亡、线粒体功能、蛋白质生物合成和RNA结合相关的基因下调。结论。复杂感染性病毒（例如 HIV-1）的基因表达谱分析可能有助于阐明与病毒感染相关的功能基因组关系。
Background. An assessment of biomarkers from an analysis of human peripheral blood mononuclear cell gene-expression profiles was made, to acquire an understanding of transcriptional changes associated with human immunodeficiency virus type 1 (HIV- 1) infection in vivo.Methods. Supervised learning algorithms were used to create signature gene sets that could be used to distinguish seropositive from seronegative samples and delineate changes in disease status during the early stages of infection. Bioinformatic tools were used to classify persons and to functionally characterize groups of differentially expressed genes, to elucidate the impact of viral infection on host cell gene-expression patterns.Results. A 10-gene signature set that could be used to accurately determine the HIV-1 serostatus was identified. A 6-gene signature set was used to distinguish seropositive persons exhibiting differential changes in CD4(+) T cell counts, with 93% accuracy. Functional classification of differentially expressed genes in HIV- 1 indicated a preponderance of down-regulated genes with functions related to the immune response and apoptosis. Hierarchical cluster analysis in persons whose CD4+ T cell counts increased, compared with that in persons whose CD4+ T cell counts decreased, was characterized by the down-regulation of genes associated with apoptosis, mitochondrial function, protein biosynthesis, and RNA binding.Conclusions. Gene-expression profile analysis of a complex infectious virus, such as HIV-1, may be useful to elucidate the functional genomic relationships associated with viral infection.