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Multi-ancestry genome-wide association and tissue/cell-type enrichment analyses. (A) Manhattan plot of multi-ancestry GWAS results for CK across all autosomes; the red dashed line denotes the genome-wide significance threshold (P = 5 × 10 −8 ). Previously unreported lead SNPs are shown in red; for clarity only previously unreported loci with exonic lead SNPs are annotated with mapped genes. The y axis is capped at −log 10 (P) = 50; peaks exceeding this value are truncated and marked with arrows, with lead variants and mapped genes rs7305678 (CD163/APOBEC1), rs11559024 (CKM), rs12975366 (LILRB5) and rs7481951 (ANO5). (B & C) MAGMA tissue and cell-type enrichment analysis based on (B) GTEx expression data, (C) Human Protein <t>Atlas</t> <t>single-cell</t> expression profiles; the dashed line indicates the Bonferroni-corrected significance threshold, and significant tissues and cell types are shown in red.
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Multi-ancestry genome-wide association and tissue/cell-type enrichment analyses. (A) Manhattan plot of multi-ancestry GWAS results for CK across all autosomes; the red dashed line denotes the genome-wide significance threshold (P = 5 × 10 −8 ). Previously unreported lead SNPs are shown in red; for clarity only previously unreported loci with exonic lead SNPs are annotated with mapped genes. The y axis is capped at −log 10 (P) = 50; peaks exceeding this value are truncated and marked with arrows, with lead variants and mapped genes rs7305678 (CD163/APOBEC1), rs11559024 (CKM), rs12975366 (LILRB5) and rs7481951 (ANO5). (B & C) MAGMA tissue and cell-type enrichment analysis based on (B) GTEx expression data, (C) Human Protein <t>Atlas</t> <t>single-cell</t> expression profiles; the dashed line indicates the Bonferroni-corrected significance threshold, and significant tissues and cell types are shown in red.
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Multi-ancestry genome-wide association and tissue/cell-type enrichment analyses. (A) Manhattan plot of multi-ancestry GWAS results for CK across all autosomes; the red dashed line denotes the genome-wide significance threshold (P = 5 × 10 −8 ). Previously unreported lead SNPs are shown in red; for clarity only previously unreported loci with exonic lead SNPs are annotated with mapped genes. The y axis is capped at −log 10 (P) = 50; peaks exceeding this value are truncated and marked with arrows, with lead variants and mapped genes rs7305678 (CD163/APOBEC1), rs11559024 (CKM), rs12975366 (LILRB5) and rs7481951 (ANO5). (B & C) MAGMA tissue and cell-type enrichment analysis based on (B) GTEx expression data, (C) Human Protein <t>Atlas</t> <t>single-cell</t> expression profiles; the dashed line indicates the Bonferroni-corrected significance threshold, and significant tissues and cell types are shown in red.
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Multi-ancestry genome-wide association and tissue/cell-type enrichment analyses. (A) Manhattan plot of multi-ancestry GWAS results for CK across all autosomes; the red dashed line denotes the genome-wide significance threshold (P = 5 × 10 −8 ). Previously unreported lead SNPs are shown in red; for clarity only previously unreported loci with exonic lead SNPs are annotated with mapped genes. The y axis is capped at −log 10 (P) = 50; peaks exceeding this value are truncated and marked with arrows, with lead variants and mapped genes rs7305678 (CD163/APOBEC1), rs11559024 (CKM), rs12975366 (LILRB5) and rs7481951 (ANO5). (B & C) MAGMA tissue and cell-type enrichment analysis based on (B) GTEx expression data, (C) Human Protein <t>Atlas</t> <t>single-cell</t> expression profiles; the dashed line indicates the Bonferroni-corrected significance threshold, and significant tissues and cell types are shown in red.
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a UMAP plots of CD3D + CD4 + cells generated with integrated gene expression data <t>from</t> <t>single-cell</t> RNA sequencing (scRNA-seq) of peripheral blood (PB) and tumor-infiltrating lymphocytes (TILs) derived from 8 stage I-II non-small cell lung cancer patients. All 79,130 CD3D + CD4 + cells (65,572 PB-CD3D + CD4 + cells and 13,558 TIL-CD3D + CD4 + cells) were categorized into 27 clusters, as illustrated in the UMAP plot. b The expression of SELL in the UMAP plot is indicated. The area outlined by the red dotted line represents clusters composed of effector T cells with downregulated expression of SELL . c On the basis of T-cell receptor (TCR) repertoire analysis using scTCR-seq, cells belonging to TCR clonotypes with two or more cells detected were mapped as pink dots on the UMAP plot. Although Foxp3 + Tregs in TILs included multicellular TCR clonotype cells, most effector multicellular TCR clonotype cells belong to clusters in which SELL expression was downregulated (outlined by a red dotted line). d Expression of FoxP3 in the UMAP plot is indicated. e Expression patterns of the 58 signature genes from sorted Th1, Th7R, and Th17 cells, and clusters PB-13 + 26, 18 + 21, and 14 from unsupervised clustering of surgical samples are shown as a heatmap. Predicted probabilities and cosine similarity index with sorted Th are indicated. f Distribution of cells with the same TCR clonotype found in the TIL-13, TIL-14, TIL-18, and TIL-21 clusters in both the TIL and the PB clusters. Each color represents cluster identity as defined in the UMAP plot (Fig. 1a). The TCR clonotypes found in the TIL-13 cluster were found almost exclusively in cluster 13 in TILs or PB. However, TIL-21 clonotypes were shared with the cluster 18 in TILs. g The number of cells in each TIL and PB cluster, those belonging to the 13, 14, 18, 21, and 26 clusters, are plotted in a color-coded stacked bar graph divided by five levels of clonal expansion. The PB-18 cluster had very few multicellular TCR clonotypes, whereas the TIL-18 cluster contained substantially expanded TCR clonotypes. h UMAP plot based on the WNN method using nuclear mRNA expression (nRNA) and chromatin accessibility (ATAC) profiles. A total of 10,699 nuclei were classified into 27 distinct clusters. i Annotation of Th1, Th7R, Th17, Treg and other cell type were visualized in a UMAP plot. j Nuclear mRNA expression patterns of 58 signature genes. The results of the cosine similarity analysis of the gene expression patterns in each cluster compared with the gene expression of the sorted Th cells are also presented. k Gene activity of 54 of 58 signature genes were shown as heatmap. The results of the cosine similarity analysis of the gene expression patterns in each cluster compared with those in the sorted Th cells are also presented.
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Image Search Results


Multi-ancestry genome-wide association and tissue/cell-type enrichment analyses. (A) Manhattan plot of multi-ancestry GWAS results for CK across all autosomes; the red dashed line denotes the genome-wide significance threshold (P = 5 × 10 −8 ). Previously unreported lead SNPs are shown in red; for clarity only previously unreported loci with exonic lead SNPs are annotated with mapped genes. The y axis is capped at −log 10 (P) = 50; peaks exceeding this value are truncated and marked with arrows, with lead variants and mapped genes rs7305678 (CD163/APOBEC1), rs11559024 (CKM), rs12975366 (LILRB5) and rs7481951 (ANO5). (B & C) MAGMA tissue and cell-type enrichment analysis based on (B) GTEx expression data, (C) Human Protein Atlas single-cell expression profiles; the dashed line indicates the Bonferroni-corrected significance threshold, and significant tissues and cell types are shown in red.

Journal: eBioMedicine

Article Title: Multi-ancestry genome-wide association study of serum creatine kinase implicates myopathy genes and muscle pathways

doi: 10.1016/j.ebiom.2026.106274

Figure Lengend Snippet: Multi-ancestry genome-wide association and tissue/cell-type enrichment analyses. (A) Manhattan plot of multi-ancestry GWAS results for CK across all autosomes; the red dashed line denotes the genome-wide significance threshold (P = 5 × 10 −8 ). Previously unreported lead SNPs are shown in red; for clarity only previously unreported loci with exonic lead SNPs are annotated with mapped genes. The y axis is capped at −log 10 (P) = 50; peaks exceeding this value are truncated and marked with arrows, with lead variants and mapped genes rs7305678 (CD163/APOBEC1), rs11559024 (CKM), rs12975366 (LILRB5) and rs7481951 (ANO5). (B & C) MAGMA tissue and cell-type enrichment analysis based on (B) GTEx expression data, (C) Human Protein Atlas single-cell expression profiles; the dashed line indicates the Bonferroni-corrected significance threshold, and significant tissues and cell types are shown in red.

Article Snippet: The y axis is capped at −log 10 (P) = 50; peaks exceeding this value are truncated and marked with arrows, with lead variants and mapped genes rs7305678 (CD163/APOBEC1), rs11559024 (CKM), rs12975366 (LILRB5) and rs7481951 (ANO5). (B & C) MAGMA tissue and cell-type enrichment analysis based on (B) GTEx expression data, (C) Human Protein Atlas single-cell expression profiles; the dashed line indicates the Bonferroni-corrected significance threshold, and significant tissues and cell types are shown in red.

Techniques: GWAS, Genome Wide, Expressing, Single Cell

a UMAP plots of CD3D + CD4 + cells generated with integrated gene expression data from single-cell RNA sequencing (scRNA-seq) of peripheral blood (PB) and tumor-infiltrating lymphocytes (TILs) derived from 8 stage I-II non-small cell lung cancer patients. All 79,130 CD3D + CD4 + cells (65,572 PB-CD3D + CD4 + cells and 13,558 TIL-CD3D + CD4 + cells) were categorized into 27 clusters, as illustrated in the UMAP plot. b The expression of SELL in the UMAP plot is indicated. The area outlined by the red dotted line represents clusters composed of effector T cells with downregulated expression of SELL . c On the basis of T-cell receptor (TCR) repertoire analysis using scTCR-seq, cells belonging to TCR clonotypes with two or more cells detected were mapped as pink dots on the UMAP plot. Although Foxp3 + Tregs in TILs included multicellular TCR clonotype cells, most effector multicellular TCR clonotype cells belong to clusters in which SELL expression was downregulated (outlined by a red dotted line). d Expression of FoxP3 in the UMAP plot is indicated. e Expression patterns of the 58 signature genes from sorted Th1, Th7R, and Th17 cells, and clusters PB-13 + 26, 18 + 21, and 14 from unsupervised clustering of surgical samples are shown as a heatmap. Predicted probabilities and cosine similarity index with sorted Th are indicated. f Distribution of cells with the same TCR clonotype found in the TIL-13, TIL-14, TIL-18, and TIL-21 clusters in both the TIL and the PB clusters. Each color represents cluster identity as defined in the UMAP plot (Fig. 1a). The TCR clonotypes found in the TIL-13 cluster were found almost exclusively in cluster 13 in TILs or PB. However, TIL-21 clonotypes were shared with the cluster 18 in TILs. g The number of cells in each TIL and PB cluster, those belonging to the 13, 14, 18, 21, and 26 clusters, are plotted in a color-coded stacked bar graph divided by five levels of clonal expansion. The PB-18 cluster had very few multicellular TCR clonotypes, whereas the TIL-18 cluster contained substantially expanded TCR clonotypes. h UMAP plot based on the WNN method using nuclear mRNA expression (nRNA) and chromatin accessibility (ATAC) profiles. A total of 10,699 nuclei were classified into 27 distinct clusters. i Annotation of Th1, Th7R, Th17, Treg and other cell type were visualized in a UMAP plot. j Nuclear mRNA expression patterns of 58 signature genes. The results of the cosine similarity analysis of the gene expression patterns in each cluster compared with the gene expression of the sorted Th cells are also presented. k Gene activity of 54 of 58 signature genes were shown as heatmap. The results of the cosine similarity analysis of the gene expression patterns in each cluster compared with those in the sorted Th cells are also presented.

Journal: Nature Communications

Article Title: The CD4 + T cell population partners with Tpex CD8 + T cells to mediate antitumor immunity in the tumor microenvironment

doi: 10.1038/s41467-026-71161-0

Figure Lengend Snippet: a UMAP plots of CD3D + CD4 + cells generated with integrated gene expression data from single-cell RNA sequencing (scRNA-seq) of peripheral blood (PB) and tumor-infiltrating lymphocytes (TILs) derived from 8 stage I-II non-small cell lung cancer patients. All 79,130 CD3D + CD4 + cells (65,572 PB-CD3D + CD4 + cells and 13,558 TIL-CD3D + CD4 + cells) were categorized into 27 clusters, as illustrated in the UMAP plot. b The expression of SELL in the UMAP plot is indicated. The area outlined by the red dotted line represents clusters composed of effector T cells with downregulated expression of SELL . c On the basis of T-cell receptor (TCR) repertoire analysis using scTCR-seq, cells belonging to TCR clonotypes with two or more cells detected were mapped as pink dots on the UMAP plot. Although Foxp3 + Tregs in TILs included multicellular TCR clonotype cells, most effector multicellular TCR clonotype cells belong to clusters in which SELL expression was downregulated (outlined by a red dotted line). d Expression of FoxP3 in the UMAP plot is indicated. e Expression patterns of the 58 signature genes from sorted Th1, Th7R, and Th17 cells, and clusters PB-13 + 26, 18 + 21, and 14 from unsupervised clustering of surgical samples are shown as a heatmap. Predicted probabilities and cosine similarity index with sorted Th are indicated. f Distribution of cells with the same TCR clonotype found in the TIL-13, TIL-14, TIL-18, and TIL-21 clusters in both the TIL and the PB clusters. Each color represents cluster identity as defined in the UMAP plot (Fig. 1a). The TCR clonotypes found in the TIL-13 cluster were found almost exclusively in cluster 13 in TILs or PB. However, TIL-21 clonotypes were shared with the cluster 18 in TILs. g The number of cells in each TIL and PB cluster, those belonging to the 13, 14, 18, 21, and 26 clusters, are plotted in a color-coded stacked bar graph divided by five levels of clonal expansion. The PB-18 cluster had very few multicellular TCR clonotypes, whereas the TIL-18 cluster contained substantially expanded TCR clonotypes. h UMAP plot based on the WNN method using nuclear mRNA expression (nRNA) and chromatin accessibility (ATAC) profiles. A total of 10,699 nuclei were classified into 27 distinct clusters. i Annotation of Th1, Th7R, Th17, Treg and other cell type were visualized in a UMAP plot. j Nuclear mRNA expression patterns of 58 signature genes. The results of the cosine similarity analysis of the gene expression patterns in each cluster compared with the gene expression of the sorted Th cells are also presented. k Gene activity of 54 of 58 signature genes were shown as heatmap. The results of the cosine similarity analysis of the gene expression patterns in each cluster compared with those in the sorted Th cells are also presented.

Article Snippet: All single-cell RNA-seq and scTCR-seq libraries were constructed using the Chromium controller and Chromium Single-Cell Immune Profiling v2 kit (10x Genomics Inc., Pleasanton, CA, USA) to analyze gene expression differences and T-cell receptor (TCR) repertoires among T-cell subpopulations.

Techniques: Generated, Gene Expression, Single Cell, RNA Sequencing, Derivative Assay, Expressing, Activity Assay

a UMAP plots of CD3D + CD8 + cells derived from tumor-infiltrating lymphocytes (TILs) were presented. UMAP plots were generated using integrated gene expression data from single-cell RNA sequencing (scRNA-seq) ( n = 8). All 25,728 CD3D + CD8 + cells (17,997 PB-CD3D + CD8 + cells and 7,731 TIL-CD3D + CD8 + cells) were divided into 15 clusters via unsupervised clustering. b The expression of the genes GZMB and GZMK in the UMAP plot (left: TIL; right: PB) is shown. The expression of GZMB and GZMK in each cluster is also shown in violin plots, with the mean indicated by a red horizontal line. c The cell-level expression patterns of GZMB and GZMK are shown in the UMAP plot. d Heatmap illustrating the expression of signature genes of precursor exhausted CD8 + T cells (Tpex) in each TIL CD8 + T-cell cluster, excluding the MAIT cluster. e Subtraction density plot of TILs and PB cells. The density was calculated for each grid with a size of 0.2 on the UMAP plot. The intensity of the red color indicates the TIL-dominant density, whereas the intensity of the blue color indicates the PB-dominant density. f The results of RNA velocity analysis of TILs and PB are shown as a stream plot.

Journal: Nature Communications

Article Title: The CD4 + T cell population partners with Tpex CD8 + T cells to mediate antitumor immunity in the tumor microenvironment

doi: 10.1038/s41467-026-71161-0

Figure Lengend Snippet: a UMAP plots of CD3D + CD8 + cells derived from tumor-infiltrating lymphocytes (TILs) were presented. UMAP plots were generated using integrated gene expression data from single-cell RNA sequencing (scRNA-seq) ( n = 8). All 25,728 CD3D + CD8 + cells (17,997 PB-CD3D + CD8 + cells and 7,731 TIL-CD3D + CD8 + cells) were divided into 15 clusters via unsupervised clustering. b The expression of the genes GZMB and GZMK in the UMAP plot (left: TIL; right: PB) is shown. The expression of GZMB and GZMK in each cluster is also shown in violin plots, with the mean indicated by a red horizontal line. c The cell-level expression patterns of GZMB and GZMK are shown in the UMAP plot. d Heatmap illustrating the expression of signature genes of precursor exhausted CD8 + T cells (Tpex) in each TIL CD8 + T-cell cluster, excluding the MAIT cluster. e Subtraction density plot of TILs and PB cells. The density was calculated for each grid with a size of 0.2 on the UMAP plot. The intensity of the red color indicates the TIL-dominant density, whereas the intensity of the blue color indicates the PB-dominant density. f The results of RNA velocity analysis of TILs and PB are shown as a stream plot.

Article Snippet: All single-cell RNA-seq and scTCR-seq libraries were constructed using the Chromium controller and Chromium Single-Cell Immune Profiling v2 kit (10x Genomics Inc., Pleasanton, CA, USA) to analyze gene expression differences and T-cell receptor (TCR) repertoires among T-cell subpopulations.

Techniques: Derivative Assay, Generated, Gene Expression, Single Cell, RNA Sequencing, Expressing

a–c Hyperion (imaging mass cytometry) analysis of lung cancer tissue adjacent to tertiary lymphoid structures (TLS) (a–c, Supplementary Table ). Scale bars, 200 μm (upper two images in a and all images in b , c ) and 300 μm (lower two images in a ). ( a ) Spatial distribution of MECA-79⁺CD31⁺ high endothelial venules (HEVs), CXCR3⁺CCR6⁺ Th7R cells, GZMK⁺GZMB⁻ Tpex cells, and GZMB⁺ CD8⁺ T cells in the TLS-adjacent tumor region. b Cell segmentation–based visualization of single-cell marker expression and corresponding cell-type annotations derived from Hyperion analysis. c Spatial localization of B cells, Tpex, Th7R, and GZMB⁺ CD8⁺ T cells, together with the results of neighborhood analysis.

Journal: Nature Communications

Article Title: The CD4 + T cell population partners with Tpex CD8 + T cells to mediate antitumor immunity in the tumor microenvironment

doi: 10.1038/s41467-026-71161-0

Figure Lengend Snippet: a–c Hyperion (imaging mass cytometry) analysis of lung cancer tissue adjacent to tertiary lymphoid structures (TLS) (a–c, Supplementary Table ). Scale bars, 200 μm (upper two images in a and all images in b , c ) and 300 μm (lower two images in a ). ( a ) Spatial distribution of MECA-79⁺CD31⁺ high endothelial venules (HEVs), CXCR3⁺CCR6⁺ Th7R cells, GZMK⁺GZMB⁻ Tpex cells, and GZMB⁺ CD8⁺ T cells in the TLS-adjacent tumor region. b Cell segmentation–based visualization of single-cell marker expression and corresponding cell-type annotations derived from Hyperion analysis. c Spatial localization of B cells, Tpex, Th7R, and GZMB⁺ CD8⁺ T cells, together with the results of neighborhood analysis.

Article Snippet: All single-cell RNA-seq and scTCR-seq libraries were constructed using the Chromium controller and Chromium Single-Cell Immune Profiling v2 kit (10x Genomics Inc., Pleasanton, CA, USA) to analyze gene expression differences and T-cell receptor (TCR) repertoires among T-cell subpopulations.

Techniques: Imaging, Mass Cytometry, Single Cell, Marker, Expressing, Derivative Assay