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HNFL mice recapitulate a potent and balanced human antiviral response against SARS-CoV-2 infection (A) Cluster heatmap representing the top 33 proteins significantly (p ≤ 0.05) up- ( Z > 0) and downregulated ( Z < 0) in HNFL-LX at 2 DPI (10 6 PFU, n = 4) in comparison with naive (n = 4) HNFL-LX. (B) Relative differential expression of the set of 33 selected proteins in HNFL-LX (n = 4) and NRGL-LX (n = 4) at 2 DPI (10 6 PFU) represented through a semi-cluster heatmap. Proteins significantly (p ≤ 0.05) up- ( Z > 0) and downregulated ( Z < 0) are labeled in red. (C and D) Differentially expressed proteins in HNFL-LX (C) or NRGL-LX (D) at 2 DPI. Proteins with p ≤ 0.05 (horizontal dashed line) and with logFC ≥ 1 or ≤ −1 (vertical dashed lines) are considered significantly up- or downregulated, respectively. Naive n = 4; 2 DPI n = 4. (E and F) Differentially phosphorylated proteins at 2 DPI in HNFL-LX (E) and NRGL-LX (F). Proteins with p ≤ 0.05 (horizontal dashed line) and with logFC ≥ 1 or ≤ −1 (vertical dashed lines) are considered significantly up- or downregulated, respectively. Naive n = 4; 2 DPI n = 4. (G and H) Significantly (p ≤ 0.05) differentially expressed genes (upregulated, red; downregulated, blue) in HNFL-LX at 2 (G) and 7 DPI (H) following infection (10 6 PFU) in comparison with naive HNFL-LX. Fold changes were computed using MAST (Model-based Analysis of Single-Cell Transcriptomics) from pooled scRNA-seq clusters. Transcripts with p ≤ 10 −200 (horizontal dotted line) and with log2 fold change ≥ 0.2 or ≤ −0.2 (vertical dotted lines) are highlighted. Naive n = 2; 2 DPI n = 3. (I) List of PDGs found to be upregulated by both proteomics and <t>transcriptomic</t> approaches in inoculated HNFL-LX (YES) or solely via the proteomic approach (NO). Only PDGs found to be upregulated through both approaches were considered as definitive PDGs. (J–L) Differentially expressed transcripts in inoculated (J, 2 DPI; K, 7 DPI; 10 6 PFU) and contralateral non-inoculated NRGL-LX (L, 7 DPI) in comparison with naive NRGL-LX. Transcripts with p adj ≤ 0.05 and with log2 fold change ≥ 2 are considered significantly up- (red) or downregulated (blue). Naive n = 3; 2 DPI n = 4; 7 DPI n = 6; CL/contralateral n = 3. (M) Number of differentially up- (red) or downregulated (blue) genes per time point (2 and 7 DPI) and infection settings (inoculated/CL) in NRGL-LX. Naive n = 3; 2 DPI n = 4; 7 DP n = 6; CL/contralateral n = 3. See also <xref ref-type=Figure S6 ; Tables S2 , , and . " width="250" height="auto" />
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HNFL mice recapitulate a potent and balanced human antiviral response against SARS-CoV-2 infection (A) Cluster heatmap representing the top 33 proteins significantly (p ≤ 0.05) up- ( Z > 0) and downregulated ( Z < 0) in HNFL-LX at 2 DPI (10 6 PFU, n = 4) in comparison with naive (n = 4) HNFL-LX. (B) Relative differential expression of the set of 33 selected proteins in HNFL-LX (n = 4) and NRGL-LX (n = 4) at 2 DPI (10 6 PFU) represented through a semi-cluster heatmap. Proteins significantly (p ≤ 0.05) up- ( Z > 0) and downregulated ( Z < 0) are labeled in red. (C and D) Differentially expressed proteins in HNFL-LX (C) or NRGL-LX (D) at 2 DPI. Proteins with p ≤ 0.05 (horizontal dashed line) and with logFC ≥ 1 or ≤ −1 (vertical dashed lines) are considered significantly up- or downregulated, respectively. Naive n = 4; 2 DPI n = 4. (E and F) Differentially phosphorylated proteins at 2 DPI in HNFL-LX (E) and NRGL-LX (F). Proteins with p ≤ 0.05 (horizontal dashed line) and with logFC ≥ 1 or ≤ −1 (vertical dashed lines) are considered significantly up- or downregulated, respectively. Naive n = 4; 2 DPI n = 4. (G and H) Significantly (p ≤ 0.05) differentially expressed genes (upregulated, red; downregulated, blue) in HNFL-LX at 2 (G) and 7 DPI (H) following infection (10 6 PFU) in comparison with naive HNFL-LX. Fold changes were computed using MAST (Model-based Analysis of Single-Cell Transcriptomics) from pooled scRNA-seq clusters. Transcripts with p ≤ 10 −200 (horizontal dotted line) and with log2 fold change ≥ 0.2 or ≤ −0.2 (vertical dotted lines) are highlighted. Naive n = 2; 2 DPI n = 3. (I) List of PDGs found to be upregulated by both proteomics and transcriptomic approaches in inoculated HNFL-LX (YES) or solely via the proteomic approach (NO). Only PDGs found to be upregulated through both approaches were considered as definitive PDGs. (J–L) Differentially expressed transcripts in inoculated (J, 2 DPI; K, 7 DPI; 10 6 PFU) and contralateral non-inoculated NRGL-LX (L, 7 DPI) in comparison with naive NRGL-LX. Transcripts with p adj ≤ 0.05 and with log2 fold change ≥ 2 are considered significantly up- (red) or downregulated (blue). Naive n = 3; 2 DPI n = 4; 7 DPI n = 6; CL/contralateral n = 3. (M) Number of differentially up- (red) or downregulated (blue) genes per time point (2 and 7 DPI) and infection settings (inoculated/CL) in NRGL-LX. Naive n = 3; 2 DPI n = 4; 7 DP n = 6; CL/contralateral n = 3. See also <xref ref-type=Figure S6 ; Tables S2 , , and . " width="100%" height="100%">

Journal: Cell Reports

Article Title: Humanized mice reveal a macrophage-enriched gene signature defining human lung tissue protection during SARS-CoV-2 infection

doi: 10.1016/j.celrep.2022.110714

Figure Lengend Snippet: HNFL mice recapitulate a potent and balanced human antiviral response against SARS-CoV-2 infection (A) Cluster heatmap representing the top 33 proteins significantly (p ≤ 0.05) up- ( Z > 0) and downregulated ( Z < 0) in HNFL-LX at 2 DPI (10 6 PFU, n = 4) in comparison with naive (n = 4) HNFL-LX. (B) Relative differential expression of the set of 33 selected proteins in HNFL-LX (n = 4) and NRGL-LX (n = 4) at 2 DPI (10 6 PFU) represented through a semi-cluster heatmap. Proteins significantly (p ≤ 0.05) up- ( Z > 0) and downregulated ( Z < 0) are labeled in red. (C and D) Differentially expressed proteins in HNFL-LX (C) or NRGL-LX (D) at 2 DPI. Proteins with p ≤ 0.05 (horizontal dashed line) and with logFC ≥ 1 or ≤ −1 (vertical dashed lines) are considered significantly up- or downregulated, respectively. Naive n = 4; 2 DPI n = 4. (E and F) Differentially phosphorylated proteins at 2 DPI in HNFL-LX (E) and NRGL-LX (F). Proteins with p ≤ 0.05 (horizontal dashed line) and with logFC ≥ 1 or ≤ −1 (vertical dashed lines) are considered significantly up- or downregulated, respectively. Naive n = 4; 2 DPI n = 4. (G and H) Significantly (p ≤ 0.05) differentially expressed genes (upregulated, red; downregulated, blue) in HNFL-LX at 2 (G) and 7 DPI (H) following infection (10 6 PFU) in comparison with naive HNFL-LX. Fold changes were computed using MAST (Model-based Analysis of Single-Cell Transcriptomics) from pooled scRNA-seq clusters. Transcripts with p ≤ 10 −200 (horizontal dotted line) and with log2 fold change ≥ 0.2 or ≤ −0.2 (vertical dotted lines) are highlighted. Naive n = 2; 2 DPI n = 3. (I) List of PDGs found to be upregulated by both proteomics and transcriptomic approaches in inoculated HNFL-LX (YES) or solely via the proteomic approach (NO). Only PDGs found to be upregulated through both approaches were considered as definitive PDGs. (J–L) Differentially expressed transcripts in inoculated (J, 2 DPI; K, 7 DPI; 10 6 PFU) and contralateral non-inoculated NRGL-LX (L, 7 DPI) in comparison with naive NRGL-LX. Transcripts with p adj ≤ 0.05 and with log2 fold change ≥ 2 are considered significantly up- (red) or downregulated (blue). Naive n = 3; 2 DPI n = 4; 7 DPI n = 6; CL/contralateral n = 3. (M) Number of differentially up- (red) or downregulated (blue) genes per time point (2 and 7 DPI) and infection settings (inoculated/CL) in NRGL-LX. Naive n = 3; 2 DPI n = 4; 7 DP n = 6; CL/contralateral n = 3. See also Figure S6 ; Tables S2 , , and .

Article Snippet: • Transcriptomic data from single cell RNA sequencing are available through the National Center for Biotechnology Information Gene Expression Omnibus (GEO) under series accession no. GSE180063 .

Techniques: Infection, Comparison, Quantitative Proteomics, Labeling, Single-cell Transcriptomics