Systems biology applications to study mechanisms of human immunodeficiency virus latency and reactivation

Table 4 Features of gene expression studies comparing suberoylanilide hydroxamic acid -treated and untreated primary cells

Study characteristics	Beliakova-Bethell et al[96]	Reardon et al[100]	White et al[99]	Mohammadi et al[42]	Elliott et al[25]
Cells used	Primary CD4+ T cells	Primary CD4+ T cells	Primary CD4+ T cells	In vitro primary CD4+ T cell latency model	Total blood from HIV-infected individuals on cART
Concentration or dose of SAHA	0.34 μmol/L	0.34, 1, 3, 10 μmol/L	1 μmol/L	0.5 μmol/L	400 mg orally once daily
Time of treatment	24 h	24 h	24 h	8 h and 24 h	14 d (samples analyzed at 2, 8 h; 1, 14 and 84 d)
Experiment replicates	9	6	6	Not reported	9
Gene expression profiling platform	Microarrays (Illumina HT12 Beadchips version 3)	Microarrays (Illumina HT12 Beadchips version 3)	Microarrays (Illumina HT12 Beadchips version 3)	RNA-Seq (polyA RNA library; Illumina HiSeq2000)	Microarrays (Illumina Human HT12 version 4)
Methods to identify DEGs	Multivariate permutation test (BRB-Array tools)	Dose-response analysis using likelihood ratio test (Isogene) with Bonferroni correction (P < 0.05)	Linear modeling (limma, FDR P < 0.05)	Generalized linear modeling (DESeq, FDR < 0.05)	Linear modeling (limma, P < 0.05)
Databases used for functional analyses	GO consortium, KEGG and Biocarta pathways (BRB-Array Tools), MetaCore networks	GO consortium, KEGG and Biocarta pathways (BRB-Array Tools), MetaCore networks	GO consortium, KEGG pathways (FAIME), MetaCore networks	Reactome pathways Ver.40; MsigDb	IPA, MsigDb
Total number of DEGs	1847	3477	2982	1289	Not reported

cART: Combination antiretroviral therapy; polyA: Polyadenylated; DEGs: Differentially expressed genes; BRB: Biometric Research Branch; FDR: False discovery rate; GO: Gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; MsigDb: Molecular Signature database; FAIME: Functional Analysis of Individual Microarray Expression; IPA: Ingenuity Pathway Analysis; HIV: Human immunodeficiency virus.