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Fig. 4 | Genome Biology

Fig. 4

From: A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers

Fig. 4

Immunomodulators can alter the fractional abundance of the c1 mDC phenotype. a Top: Schematic of bulk expression data (Bi) from publicly available perturbation data. Bottom: Each cell’s expression profile (C1j) is correlated with all Bi so as to compare similarities of the single-cell cluster 1 to all bulk expression profiles. b Volcano plot of negative log meta-analysis false discovery rate (FDR) vs mean difference in “TLR stimulation score” between c1 and c3–5. Scores are computed from weighted correlations between single-cell profiles and transcriptional patterns from human DCs (see “Methods”) after 48 h of stimulation with media control (black) or agonists for either TLR2 (PAM3CSK4, dark blue), TLR3 (Poly I:C, green), TLR4 (LPS, orange), TLR7/8 (Gard, purple), or TLR9 (CpG, light blue). Tests reproduced with FDR < 0.01 in both stratified analyses are highlighted in blue. c Proportion of CD64Hi,PDL1Hi cells among mDCs from PBMCs isolated from HIV-negative individuals cultured in the absence or the presence of VSV-G pseudotyped HIV-1, alone or in combination with TLR ligands (TLRL: TLR2L, PGNA, n = 11; TLR3L, Poly I:C, n = 11; TLR4L, LPS, n = 8; TLR8L, CL097, n = 11; Methods). Statistical significance was calculated using Kruskal–Wallis and Dunn’s tests (**, p < 0.01). d Proportions of CD64Hi, PD-L1Hi cells among mDCs from healthy individuals (indigo) and elite controllers (olive) cultured in the absence or the presence of Poly I:C and polymer nanoparticles loaded with single-stranded (ss) or double stranded (ds) 100 nucleotide HIV-1 DNA (see “Methods”; n = 8, HIV negative individuals; n = 7, ECs). Statistical significance was calculated using either two-tailed Wilcoxon signed-rank test (black) or two-tailed Mann–Whiney test (red) to compare differences within or among patient groups, respectively (**, p < 0.01; *, p < 0.05). e Proportion of proliferating CD4+ or CD8+ T cells after culture with Hi or Lo mDC from a HD stimulated with TLRL3 and nanoparticles containing gag single-stranded DNA (*, p < 0.05; two-tailed Wilcoxon signed-rank test. n = 6). f Volcano plot of negative log IDR vs mean difference in upstream regulatory score between c1 and c3–5 based on single-cell correlations with short hairpin RNA-perturbation profiles from mouse DCs stimulated with LPS for 6 h (adapted from Chevrier et al. [32]; see “Methods”). The net effect (activate, inhibit, both) of each perturbation is denoted by color (red, blue, gray, respectively), as is its breadth (size). g Proportions of CD64Hi,PD-L1Hi cells among EC mDCs cultured in the presence or absence of virus and DMSO (control, magenta) or BX795 TBK1 inhibitor (cyan; n = 10; see “Methods”). Statistical significance was calculated using a two-tailed Wilcoxon signed-rank test (*, p < 0.05)

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