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

Table 5 Features of gene expression studies comparing cells treated with latency reversing agents of different functional classes and untreated cells

Study characteristics	Jiang et al[95]	Mohammadi et al[42]	Sung and Rice[97]	Banerjee et al[98]
Cells used	Primary cells from HIV-infected individuals on cART	In vitro primary CD4+ T cell latency model	Primary resting CD4+ T cells	J-Lat 10.6 T cell line
LRA (functional class)	Valproic acid (HDACi)	Disulfiram (alcohol dehydrogenase inhibitor)	Prostratin (PKC agonist)	JQ1 (bromodomain inhibitor)
Concentration	1 mmol/L (+20 U/mL IL-2)	0.5 μmol/L	250 ng/mL	0.1 μmol/L, 1 μmol/L
Time of treatment	6 h	8 and 24 h	48 h	24 h
Experiment replicates	4	Not reported	3	Not reported
Gene expression profiling platform	Microarrays (Agilent)	RNA-Seq (polyA RNA library; Illumina HiSeq2000)	Microarrays (Affymetrix Human Genome U133 Plus 2.0)	Microarrays (Affymetrix ST 1.0)
Methods to identify DEGs	Rosetta Resolver system (P < 0.01)	Generalized linear modeling (DESeq, FDR < 0.05)	t-test with FDR correction	ANOVA (P < 1E-5)
Databases used for functional analyses	Not used	Reactome pathways Ver.40; MsigDb	GO consortium, KEGG pathways	GO consortium
Total number of DEGs	199 (fold change > 3)	189	2514 (fold change > 1.5)	Not reported

cART: Combination antiretroviral therapy; LRA: Latency reversing agent; HDACi: Histone deacetylase inhibitor; PCK: Protein kinase C; polyA: Polyadenylated; DEGs: Differentially expressed genes; FDR: False discovery rate; ANOVA: Analysis of variance; MsigDb: Molecular Signature database; GO: Gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; LRAs: Latency reversing agents.