Journal: Genome Medicine

Article Title: A dynamic single cell-based framework for digital twins to prioritize disease genes and drug targets

doi: 10.1186/s13073-022-01048-4

Figure Lengend Snippet: Construction of MNMs and prioritization of URs. A (1) Determination of DEGs (red) in a cell type (gray). (2) Bioinformatic identification of the predicted UR of the DEGs. (3) Identification of another cell type (blue) in which that UR is differentially expressed. (4) A directed interaction from the blue to the gray cell type is formed. B Example of one MNM (at 0 h) which was constructed based on directed interactions as described in A. C MNMs created at each time point. Node sizes correspond to the number of DEGs between cells isolated from patients compared to healthy controls. Edge width represents the number of predicted URs. Edge color corresponds to the source cell. D Heatmap of top 40 URs ranked based on the number of cell types that each UR is predicted to regulate at different time points. Color intensity boxes indicate the statistical significance of predictions. Grey boxes indicate non-significant predictions. A positive z-score indicates that the direction of the differential expression matches the predicted direction (orange), while a negative z-score indicates the opposite (blue). The inserted boxes on the right correspond to the top 20 URs in the left boxes. E , F Dynamic UR-target models showing predicted cell-type targets of PDGF-BB and IL-4 in allergen-stimulated patients. Node size denotes the significance of the association (z-score)

Article Snippet: For blocking experiments, PBMCs (1 × 10 6 cells) from eight SAR patients were stimulated for 5 days with 10 μg/mL BPE in the absence or presence of either a neutralizing anti-human IL-4 antibody (MAB204) or anti-human PDGF-BB antibody (AF-220-NA, both from R&D Systems, Minneapolis, USA) at a concentration of 5 μg/mL.

Techniques: Construct, Isolation, Quantitative Proteomics

Journal: Genome Medicine

Article Title: A dynamic single cell-based framework for digital twins to prioritize disease genes and drug targets

doi: 10.1186/s13073-022-01048-4

Figure Lengend Snippet: Protein expression patterns of predicted URs in supernatants of allergen-stimulated PBMC from SAR patients and controls. A PDGF-BB, B IFN-α, and C CCL5 levels in supernatants. * P -value < 0.05, ** P -value < 0.01, Wilcoxon signed rank test

Article Snippet: For blocking experiments, PBMCs (1 × 10 6 cells) from eight SAR patients were stimulated for 5 days with 10 μg/mL BPE in the absence or presence of either a neutralizing anti-human IL-4 antibody (MAB204) or anti-human PDGF-BB antibody (AF-220-NA, both from R&D Systems, Minneapolis, USA) at a concentration of 5 μg/mL.

Techniques: Expressing

Journal: Genome Medicine

Article Title: A dynamic single cell-based framework for digital twins to prioritize disease genes and drug targets

doi: 10.1186/s13073-022-01048-4

Figure Lengend Snippet: Effects of PDGF-BB neutralization on the release of IL-6, IL-13, and VEGF from allergen-stimulated PBMC. A IL-6, B IL-13, and C VEGF levels in supernatants harvested at day 5; D allergen-specific lymphoproliferation. Box plots are shown, red lines indicate median values, * P -value < 0.05, Wilcoxon signed ranks test. The different shapes of data points represent different SAR patients

Article Snippet: For blocking experiments, PBMCs (1 × 10 6 cells) from eight SAR patients were stimulated for 5 days with 10 μg/mL BPE in the absence or presence of either a neutralizing anti-human IL-4 antibody (MAB204) or anti-human PDGF-BB antibody (AF-220-NA, both from R&D Systems, Minneapolis, USA) at a concentration of 5 μg/mL.

Techniques: Neutralization

Journal: Bone

Article Title: Preservation of Type H Vessels and Osteoblasts by Enhanced Preosteoclast Platelet-Derived Growth Factor type BB Attenuates Glucocorticoid-Induced Osteoporosis in Growing Mice

doi: 10.1016/j.bone.2018.05.025

Figure Lengend Snippet: (A-B) Representative images of immunofluorescence staining of platelet-derived growth factor type BB (PDGF-BB) (green) and tartrate-resistant acid phosphatase (TRAP) (red) with quantification of number of PDGF-BB+ TRAP+ cells (yellow) in femoral primary (A) and secondary spongiosa (B) of 6 week old Ctsk+/+ wild type (WT) and Ctsk−/− mice injected with either vehicle (veh) or prednisolone 10 mg/m2/day (pred) for 4 weeks. DAPI stains nuclei blue. Scale bar, 50 μm. (C) Bone marrow PDGF-BB concentration as analyzed by ELISA. n = 6 per group. Data shown as mean ± s.d. *P < 0.05, **P < 0.01, ***P < 0.001.

Article Snippet: We performed PDGF-BB ELISA analysis of bone marrow supernatant using a Mouse/Rat PDGF-BB Quantikine ELISA kit (R&D Systems) according to the manufacturers’ instructions.

Techniques: Immunofluorescence, Staining, Derivative Assay, Injection, Concentration Assay, Enzyme-linked Immunosorbent Assay