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

Topics {✒️}

electronic supplementary material integrating single-cell rna-sequencing supplementary information files abbreviations gwas springer nature single-cell rna sequencing funding sharing state privacy rights additional information publisher single-cell sequencing data sc-linker framework developed genome-wide association studies enhancer–gene-linking strategy large-scale association analysis scaling single-cell genomics single-cell transcriptomic architecture sc-linker heritability enrichment kaplan–meier curves demonstrating enhancer–gene-linking strategies included single-cell sequencing ras-related protein rab-31 combining single-cell technologies original author sc-linker framework nsclc single-cell datasets lung enhancer-gene links sc-linker differs utilizing sc-linker diffuse-type gastric cancers gwas information cell-cell interaction analysis single-cell sequencing conclusions kaplan–meier curves illustrating nat methods disease-dependent programs highlight cell cycle-related regulators increased receptor-ligand interactions small-cell lung cancer �disease-dependent gene programs nhgri-ebi gwas catalog heparin-binding growth factors cell-type gene program linkage disequilibrium-dependent architecture scrna-seq data sided s-ldsc tests full size image previous scrna-seq clustering compared receptor-ligand interactions

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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.
         datePublished:2025-01-23T00:00:00Z
         dateModified:2025-01-23T00:00:00Z
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            Single cell RNA seq
            CAFs
            NSCLC
            RAB31
            Cancer Research
            Oncology
            Surgical Oncology
            Health Promotion and Disease Prevention
            Biomedicine
            general
            Medicine/Public Health
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               name:Yangfan Zhou
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                        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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                        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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               name:Jianhao Chen
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                        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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      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.
      datePublished:2025-01-23T00:00:00Z
      dateModified:2025-01-23T00:00:00Z
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      pageEnd:14
      license:http://creativecommons.org/licenses/by-nc-nd/4.0/
      sameAs:https://doi.org/10.1186/s12885-025-13525-1
      keywords:
         Sc-linker
         Single cell RNA seq
         CAFs
         NSCLC
         RAB31
         Cancer Research
         Oncology
         Surgical Oncology
         Health Promotion and Disease Prevention
         Biomedicine
         general
         Medicine/Public Health
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         name:BioMed Central
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      author:
            name:Yangfan Zhou
            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
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                  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
            type:Person
            name:Liang Zhao
            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
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                  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
            type:Person
            name:Meimei Cai
            affiliation:
                  name:The First Affiliated Hospital of Xiamen University, Xiamen University
                  address:
                     name:Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
                     type:PostalAddress
                  type:Organization
            type:Person
            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
            type:Person
            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
            type:Person
            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
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            type:Person
            name:Qicong Luo
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                  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]
            type:Person
            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
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               type:PostalAddress
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      name:Liang Zhao
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            name:The First Affiliated Hospital of Xiamen University, Xiamen University
            address:
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               name:Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
               type:PostalAddress
            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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