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第44卷第6期
               ·808 ·                            南 京    医 科 大 学 学         报                        2024年6月


                A                                                B
                               GO: 0022600  GO: 0010951                                 GO: 0010951
                            0052547            GO:                          0001666 GO: 0036293  GO:
                          GO:                                              GO:
                                                 0010466
                                                                                                  0070207
                          0052548                   GO:                    0000041                   GO:
                          GO:                                              GO:
                                                     0061844
                                                                                                     0010466
                              0019730              0006959  GO:               0070206               2000117  GO:
                                        GO: 0051346 GO:  GO: 0045861            GO:

                                                                                        GO: 0018119  GO: 0017014
                          log2FC                    z⁃score
                                                                           log2FC                   z⁃score
                    Downregulated  Upregulated
                                               Decreasing  Increasing  Downregulated  Upregulated
                                                                                                Decreasing  Increasing
                      ID                 Description
                                                                      ID                 Description
                   GO:0010951 Negative regulation of endopeptidase activity
                   GO:0010466 Negative regulation of peptidase activity  GO:0010951 Negative regulation of endopeptidase activity
                                                                   GO:0070207 Protein homotrimerization
                            Antimicrobial humoral immune response mediated by anti⁃
                   GO:0061844                                      GO:0010466 Negative regulation of peptidase activity
                            microbial peptied                      GO:2000117 Negative regulation of cysteine⁃type endopeptidase activity
                   GO:0006959 Humoral immune response              GO:0017014 Protein nitrosylation
                   GO:0045861 Negative regulation of proteolysis   GO:0018119 Peptidyl⁃cysteine S⁃nitrosylation
                   GO:0051346 Negative regulation of hydrolase activity
                                                                   GO:0070206 Protein trimerization
                   GO:0019730 Antimicrobial humoral response       GO:0000041 Transition metal ion transport
                   GO:0052548 Regulation of endopeptidase activity  GO:0001666 Response to hypoxia
                   GO:0052547 Regulation of pepetidase activity
                                                                   GO:0036293 Response to decreased oxygen levels
                   GO:0022600 Digestive system process
                                  C                              Pertussis
                                                Complement and coagulation cascades
                                                        IL⁃17 signaling pathway
                                    Viral protein interaction with cytokine and cytokine receptor
                                                              Leishmaniasis
                                                            Salivary secretion
                                                          Rheumatoid arthritis
                                                    Staphylococcus aureus infection
                                                       Hematopoietic cell lineage   Gene Ratio
                                                             Chagas disease          0.05
                                                               Amoebiasis            0.10
                                                     Chemokine signaling pathway     0.15
                                                         TNF signaling pathway       0.20
                                                            ABC transporters
                                            Amino sugar and nucleotide sugar metabolism  P adjust
                                                              Legionellosis
                                                        Glutathione metabolism       0.04
                                                      Estrogen signaling pathway     0.03
                                           Kaposi sarcoma⁃associated herpesvirus infection  0.02
                                                                                     0.01
                                                          Pancreatic secretion
                                         Parathyroid hormone synthesis,secretion and action
                                                       Relaxin signaling pathway
                                                        Apelin signaling pathway
                                                         Alcoholic liver disease
                                                              Tuberculosis
                                                          Arginine biosynthesis
                                                       Renin⁃angiotensin system
                                                        Lipid and atherosclerosis
                                                                       Cluster 1 Cluster 2
                                                                       (n=48)(n=14)
                 A:The chord diagram of the biological process GO analysis for cluster 1. B:The chord diagram of the biological process GO analysis for cluster 2.
              C:The bubble plot of the KEGG pathway analysis for the two subtypes(cluster 1 and cluster 2).
                                                  图5 两种哮喘亚型富集分析
                                      Figure 5  Enrichment analysis of the two subtypes of asthma
              基因模块(图 6A~C),以基于模块特征基因的连接
                                                                3  讨 论
              性度量值作为筛选标准,确定与各亚型关系最密切
              的上调和下调基因;基于上述差异基因,cMap数据库                              哮喘由表观遗传调控和环境因素暴露相互作
              中筛选出各亚型潜在小分子药物,结合cMap分析结                          用驱动,影响着全球超过 3 亿的成人及儿童。作为
              果及相关文献,确定哮喘亚型1与哮喘亚型2最具希                           一种常见呼吸系统异质性疾病,其表型多样、潜在
              望的预测药物分别为 XMD8⁃92 和 Verrucarin⁃A(图                发病机制并不明确         [10] 。目前基于辅助性T细胞2 型
              6D,表1)。                                          (T helper type 2,Th2)状态,哮喘被分为Th2⁃高型及
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