Integrating single-cell RNA-Seq and machine learning to dissect tryptophan metabolism in ulcerative colitis
Abstract Background Ulcerative colitis (UC) is a persistent inflammatory bowels disease (IBD) characterized by immune response dysregulation and metabolic disruptions. Tryptophan metabolism has been believed as a significant factor in UC pathogenesis, with specific metabolites influencing immune mod...
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BMC
2024-12-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-05934-w |
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| author | Guorong Chen Hongying Qi Li Jiang Shijie Sun Junhai Zhang Jiali Yu Fang Liu Yanli Zhang Shiyu Du |
| author_facet | Guorong Chen Hongying Qi Li Jiang Shijie Sun Junhai Zhang Jiali Yu Fang Liu Yanli Zhang Shiyu Du |
| author_sort | Guorong Chen |
| collection | DOAJ |
| description | Abstract Background Ulcerative colitis (UC) is a persistent inflammatory bowels disease (IBD) characterized by immune response dysregulation and metabolic disruptions. Tryptophan metabolism has been believed as a significant factor in UC pathogenesis, with specific metabolites influencing immune modulation and gut microbiota interactions. However, the precise regulatory mechanisms and key genes involved remain unclear. Methods AUCell, Ucell, and other functional enrichment algorithms were utilized to determine the activation patterns of tryptophan metabolism at the UC cell level. Differential analysis identified key genes associated with tryptophan metabolism. Five machine learning algorithms, including Random Forest, Boruta algorithm, LASSO, SVM-RFE, and GBM were integrated to identify and categorize disease-specific characteristic genes. Results We observed significant heterogeneity in tryptophan metabolism activity across cell types in UC, with the highest activity levels in macrophages and fibroblasts. Among the key tryptophan metabolism-related genes, CTSS, S100A11, and TUBB were predominantly expressed in macrophages and significantly upregulated in UC, highlighting their involvement in immune dysregulation and inflammation. Cross-analysis with bulk RNA data confirmed the consistent upregulation of these genes in UC samples, highly indicating their relevance in UC pathology and potential as targets for therapeutic intervention. Conclusions This study is the first to reveal the heterogeneity of tryptophan metabolism at the single-cell level in UC, with macrophages emerging as key contributors to inflammatory processes. The identification of CTSS, S100A11, and TUBB as key regulators of tryptophan metabolism in UC underscores their potential as biomarkers and therapeutic targets. |
| format | Article |
| id | doaj-art-9780a7ea2b2d4daf8645d6c41fbd67ce |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-9780a7ea2b2d4daf8645d6c41fbd67ce2024-12-22T12:44:27ZengBMCJournal of Translational Medicine1479-58762024-12-0122111410.1186/s12967-024-05934-wIntegrating single-cell RNA-Seq and machine learning to dissect tryptophan metabolism in ulcerative colitisGuorong Chen0Hongying Qi1Li Jiang2Shijie Sun3Junhai Zhang4Jiali Yu5Fang Liu6Yanli Zhang7Shiyu Du8Department of Gastroenterology, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences)Department of Spleen and Stomach Diseases of Traditional Chinese Medicine, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences)Department of Endocrinology, Aviation General HospitalDepartment of Gastroenterology, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences)Department of Gastroenterology, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences)Department of Gastroenterology, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences)Department of Gastroenterology, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences)Department of Gastroenterology, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences)Department of Gastroenterology, China-Japan Friendship Hospital (Institute of Clinical Medical Sciences)Abstract Background Ulcerative colitis (UC) is a persistent inflammatory bowels disease (IBD) characterized by immune response dysregulation and metabolic disruptions. Tryptophan metabolism has been believed as a significant factor in UC pathogenesis, with specific metabolites influencing immune modulation and gut microbiota interactions. However, the precise regulatory mechanisms and key genes involved remain unclear. Methods AUCell, Ucell, and other functional enrichment algorithms were utilized to determine the activation patterns of tryptophan metabolism at the UC cell level. Differential analysis identified key genes associated with tryptophan metabolism. Five machine learning algorithms, including Random Forest, Boruta algorithm, LASSO, SVM-RFE, and GBM were integrated to identify and categorize disease-specific characteristic genes. Results We observed significant heterogeneity in tryptophan metabolism activity across cell types in UC, with the highest activity levels in macrophages and fibroblasts. Among the key tryptophan metabolism-related genes, CTSS, S100A11, and TUBB were predominantly expressed in macrophages and significantly upregulated in UC, highlighting their involvement in immune dysregulation and inflammation. Cross-analysis with bulk RNA data confirmed the consistent upregulation of these genes in UC samples, highly indicating their relevance in UC pathology and potential as targets for therapeutic intervention. Conclusions This study is the first to reveal the heterogeneity of tryptophan metabolism at the single-cell level in UC, with macrophages emerging as key contributors to inflammatory processes. The identification of CTSS, S100A11, and TUBB as key regulators of tryptophan metabolism in UC underscores their potential as biomarkers and therapeutic targets.https://doi.org/10.1186/s12967-024-05934-wTryptophan metabolismUlcerative colitisMacrophage |
| spellingShingle | Guorong Chen Hongying Qi Li Jiang Shijie Sun Junhai Zhang Jiali Yu Fang Liu Yanli Zhang Shiyu Du Integrating single-cell RNA-Seq and machine learning to dissect tryptophan metabolism in ulcerative colitis Journal of Translational Medicine Tryptophan metabolism Ulcerative colitis Macrophage |
| title | Integrating single-cell RNA-Seq and machine learning to dissect tryptophan metabolism in ulcerative colitis |
| title_full | Integrating single-cell RNA-Seq and machine learning to dissect tryptophan metabolism in ulcerative colitis |
| title_fullStr | Integrating single-cell RNA-Seq and machine learning to dissect tryptophan metabolism in ulcerative colitis |
| title_full_unstemmed | Integrating single-cell RNA-Seq and machine learning to dissect tryptophan metabolism in ulcerative colitis |
| title_short | Integrating single-cell RNA-Seq and machine learning to dissect tryptophan metabolism in ulcerative colitis |
| title_sort | integrating single cell rna seq and machine learning to dissect tryptophan metabolism in ulcerative colitis |
| topic | Tryptophan metabolism Ulcerative colitis Macrophage |
| url | https://doi.org/10.1186/s12967-024-05934-w |
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