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cancer, lung, cell, pubmed, article, cells, google, scholar, cas, rab, genes, cafs, fig, tumor, gene, fibroblasts, central, expression, analysis, caf, data, nsclc, singlecell, types, tissues, normal, programs, gwas, disease, cellular, type, sequencing, identified, related, additional, nat, specific, study, scrnaseq, closely, tissue, act, based, program, driver, genetic, healthy, enrichment, studies, cancerassociated,

Topics {✒️}

integrating single-cell rna-sequencing single-cell rna sequencing genome-wide association studies enhancer–gene-linking strategy large-scale association analysis kaplan–meier curves demonstrating single-cell sequencing data enhancer–gene-linking strategies ras-related protein rab-31 scaling single-cell genomics single-cell transcriptomic architecture included single-cell sequencing combining single-cell technologies lung enhancer-gene links diffuse-type gastric cancers kaplan–meier curves illustrating disease-dependent programs highlight increased receptor-ligand interactions cell-cell interaction analysis cell cycle-related regulators sc-linker framework developed �disease-dependent gene programs nhgri-ebi gwas catalog heparin-binding growth factors small-cell lung cancer linkage disequilibrium-dependent architecture nsclc single-cell datasets cell-type gene program single-cell sequencing sided s-ldsc tests full size image compared receptor-ligand interactions growth factor mdk/midkine developed disease-dependent programs integrating expression-related snps genome-wide gene sc-linker heritability enrichment bmc cancer 25 tumor malignancy-related pathways privacy choices/manage cookies previous scrna-seq clustering single-cell profiling act2-mediated lung carcinogenesis genetic association studies epithelial-mesenchymal transition irf5-mediated immune responses integrating scrna-seq sc-linker framework cell subpopulations based baseline ld model

Schema {🗺️}

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         headline:Utilizing sc-linker to integrate single-cell RNA sequencing and human genetics to identify cell types and driver genes associated with non-small cell lung cancer
         description:Genome-wide association studies (GWAS) provide a powerful method for identifying the loci and genes that contribute to disease. However, in many cases, the specific cell types and states that confer disease risk through these genes remain unknown. Determining this relationship is crucial for identifying pathogenic processes and developing therapeutic strategies. In this study, we utilized the sc-linker framework developed by Jagadeesh, which is an integrated framework that combines single-cell RNA sequencing (scRNA-seq), epigenomic single nucleotide polymorphism (SNP)-to-gene mapping, and GWAS summary statistics to infer potential cell types and diseases affected by genetic variations. Using normal cell type programs in the sc-linker, we identified type 2 alveolar cells in normal lung tissues that are closely associated with non-small cell lung cancer (NSCLC). Additionally, we identified cancer-associated fibroblasts (CAFs) associated with lung cancer using disease-dependent programs. By integrating extensive single-cell data from NSCLC, we discerned heterogeneity among CAFs subgroups. Finally, using MAGMA, we identified RAB31 as a driver gene in disease-related fibroblasts. Proteins from the RAB family are involved in the dynamic regulation of cell membrane compartments and are dysregulated in various tumor types, potentially altering biological properties such as the proliferation, migration, and invasion of cancer cells. We found that the Ras-related protein Rab-31 (RAB31) was significantly overexpressed in tumor-associated fibroblasts compared to that in normal fibroblasts and was closely associated with poor prognosis in patients with NSCLC. By integrating scRNA-seq, epigenomic, and GWAS datasets, we found that ACT2 and CAFs have specific disease heritability in lung cancer and identified the driver gene RAB31 as a potential therapeutic target.
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      headline:Utilizing sc-linker to integrate single-cell RNA sequencing and human genetics to identify cell types and driver genes associated with non-small cell lung cancer
      description:Genome-wide association studies (GWAS) provide a powerful method for identifying the loci and genes that contribute to disease. However, in many cases, the specific cell types and states that confer disease risk through these genes remain unknown. Determining this relationship is crucial for identifying pathogenic processes and developing therapeutic strategies. In this study, we utilized the sc-linker framework developed by Jagadeesh, which is an integrated framework that combines single-cell RNA sequencing (scRNA-seq), epigenomic single nucleotide polymorphism (SNP)-to-gene mapping, and GWAS summary statistics to infer potential cell types and diseases affected by genetic variations. Using normal cell type programs in the sc-linker, we identified type 2 alveolar cells in normal lung tissues that are closely associated with non-small cell lung cancer (NSCLC). Additionally, we identified cancer-associated fibroblasts (CAFs) associated with lung cancer using disease-dependent programs. By integrating extensive single-cell data from NSCLC, we discerned heterogeneity among CAFs subgroups. Finally, using MAGMA, we identified RAB31 as a driver gene in disease-related fibroblasts. Proteins from the RAB family are involved in the dynamic regulation of cell membrane compartments and are dysregulated in various tumor types, potentially altering biological properties such as the proliferation, migration, and invasion of cancer cells. We found that the Ras-related protein Rab-31 (RAB31) was significantly overexpressed in tumor-associated fibroblasts compared to that in normal fibroblasts and was closely associated with poor prognosis in patients with NSCLC. By integrating scRNA-seq, epigenomic, and GWAS datasets, we found that ACT2 and CAFs have specific disease heritability in lung cancer and identified the driver gene RAB31 as a potential therapeutic target.
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      dateModified:2025-01-23T00:00:00Z
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         NSCLC
         RAB31
         Cancer Research
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         Surgical Oncology
         Health Promotion and Disease Prevention
         Biomedicine
         general
         Medicine/Public Health
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            name:Jianhao Chen
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            type:Organization
      name:Doudou Luo
      affiliation:
            name:The First Affiliated Hospital of Xiamen University, Xiamen University
            address:
               name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
               type:PostalAddress
            type:Organization
            name:The First Affiliated Hospital of Xiamen University, Xiamen University
            address:
               name:Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
               type:PostalAddress
            type:Organization
      name:Yizhen Pang
      affiliation:
            name:The First Affiliated Hospital of Xiamen University, Xiamen University
            address:
               name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
               type:PostalAddress
            type:Organization
            name:The First Affiliated Hospital of Xiamen University, Xiamen University
            address:
               name:Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
               type:PostalAddress
            type:Organization
      name:Jianhao Chen
      affiliation:
            name:The First Affiliated Hospital of Xiamen University, Xiamen University
            address:
               name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
               type:PostalAddress
            type:Organization
            name:The First Affiliated Hospital of Xiamen University, Xiamen University
            address:
               name:Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
               type:PostalAddress
            type:Organization
      name:Qicong Luo
      affiliation:
            name:The First Affiliated Hospital of Xiamen University, Xiamen University
            address:
               name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Qin Lin
      affiliation:
            name:The First Affiliated Hospital of Xiamen University, Xiamen University
            address:
               name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
      name:Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China

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