Chujun Duan , Xiaojun Zhao , Xiao Li , Jiangang Xie , Yi Si , Linxiao Wang , Dan Wu , Yifan Wang , Shanshou Liu , Qianmei Wang , Ran Zhuang , Wen Yin , Junjie Li
{"title":"通过转录组测序鉴定肝移植过程中的枢纽基因和潜在的抑制性化合物。","authors":"Chujun Duan , Xiaojun Zhao , Xiao Li , Jiangang Xie , Yi Si , Linxiao Wang , Dan Wu , Yifan Wang , Shanshou Liu , Qianmei Wang , Ran Zhuang , Wen Yin , Junjie Li","doi":"10.1016/j.mcp.2023.101936","DOIUrl":null,"url":null,"abstract":"<div><p>Liver transplantation (LT) is the best choice for patients with end-stage liver diseases. In order to better understand pathophysiological alterations in LT, we aimed to identify potential hub genes and inhibitory compounds involved in the LT process. Four pairs of peripheral blood mononuclear cell (PBMC) samples of the LT recipients before and after surgery were collected and taken for transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the screened differentially expressed genes (DEGs) between pre- and post-operation groups. Common DEGs were obtained from GO and KEGG enriched pathways, followed by protein-protein interaction (PPI) network construction, hub gene identification, module analysis, and structure-based virtual screening process (SBVS). Compared to the pre-operation stage, 4745 genes were down-regulated and 798 up-regulated after LT. GO analysis showed that the DEGs were enriched in ribosome-related translation regulation, and KEGG analysis indicated that infection and immune-related pathways and diseases were largely enriched. A large number of down-regulated DEGs were not only associated with ribosome-related pathways but also with the alterations of epigenetic modifications, in particular ubiquitination. Moreover, through the PPI network of 29 common genes from GO and KEGG-enriched pathways, 7 hub genes were identified, including PTEN, MYC, EIF2S1, EIF4EBP1, HSP90AB1, TP53, and HSPA8, which were mainly involved in the PI3K-AKT signaling pathway. SBVS of the seed molecule PTEN (PDB code: <span>1D5R</span><svg><path></path></svg>) predicted top hits compounds that may serve as potential inhibitors of PTEN, of which the compound ZINC4235331 had the lowest binding affinity of -10 kcal/mol. The significance of screened hub genes and potential inhibitors involved in the process of LT provides novel therapeutic strategies for improving the outcomes of LT recipients during surgery.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"72 ","pages":"Article 101936"},"PeriodicalIF":2.3000,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification of hub genes and potential inhibitory compounds in the process of liver transplantation through transcriptome sequencing\",\"authors\":\"Chujun Duan , Xiaojun Zhao , Xiao Li , Jiangang Xie , Yi Si , Linxiao Wang , Dan Wu , Yifan Wang , Shanshou Liu , Qianmei Wang , Ran Zhuang , Wen Yin , Junjie Li\",\"doi\":\"10.1016/j.mcp.2023.101936\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Liver transplantation (LT) is the best choice for patients with end-stage liver diseases. In order to better understand pathophysiological alterations in LT, we aimed to identify potential hub genes and inhibitory compounds involved in the LT process. Four pairs of peripheral blood mononuclear cell (PBMC) samples of the LT recipients before and after surgery were collected and taken for transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the screened differentially expressed genes (DEGs) between pre- and post-operation groups. Common DEGs were obtained from GO and KEGG enriched pathways, followed by protein-protein interaction (PPI) network construction, hub gene identification, module analysis, and structure-based virtual screening process (SBVS). Compared to the pre-operation stage, 4745 genes were down-regulated and 798 up-regulated after LT. GO analysis showed that the DEGs were enriched in ribosome-related translation regulation, and KEGG analysis indicated that infection and immune-related pathways and diseases were largely enriched. A large number of down-regulated DEGs were not only associated with ribosome-related pathways but also with the alterations of epigenetic modifications, in particular ubiquitination. Moreover, through the PPI network of 29 common genes from GO and KEGG-enriched pathways, 7 hub genes were identified, including PTEN, MYC, EIF2S1, EIF4EBP1, HSP90AB1, TP53, and HSPA8, which were mainly involved in the PI3K-AKT signaling pathway. SBVS of the seed molecule PTEN (PDB code: <span>1D5R</span><svg><path></path></svg>) predicted top hits compounds that may serve as potential inhibitors of PTEN, of which the compound ZINC4235331 had the lowest binding affinity of -10 kcal/mol. The significance of screened hub genes and potential inhibitors involved in the process of LT provides novel therapeutic strategies for improving the outcomes of LT recipients during surgery.</p></div>\",\"PeriodicalId\":49799,\"journal\":{\"name\":\"Molecular and Cellular Probes\",\"volume\":\"72 \",\"pages\":\"Article 101936\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2023-10-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular and Cellular Probes\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0890850823000452\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Probes","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0890850823000452","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Identification of hub genes and potential inhibitory compounds in the process of liver transplantation through transcriptome sequencing
Liver transplantation (LT) is the best choice for patients with end-stage liver diseases. In order to better understand pathophysiological alterations in LT, we aimed to identify potential hub genes and inhibitory compounds involved in the LT process. Four pairs of peripheral blood mononuclear cell (PBMC) samples of the LT recipients before and after surgery were collected and taken for transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the screened differentially expressed genes (DEGs) between pre- and post-operation groups. Common DEGs were obtained from GO and KEGG enriched pathways, followed by protein-protein interaction (PPI) network construction, hub gene identification, module analysis, and structure-based virtual screening process (SBVS). Compared to the pre-operation stage, 4745 genes were down-regulated and 798 up-regulated after LT. GO analysis showed that the DEGs were enriched in ribosome-related translation regulation, and KEGG analysis indicated that infection and immune-related pathways and diseases were largely enriched. A large number of down-regulated DEGs were not only associated with ribosome-related pathways but also with the alterations of epigenetic modifications, in particular ubiquitination. Moreover, through the PPI network of 29 common genes from GO and KEGG-enriched pathways, 7 hub genes were identified, including PTEN, MYC, EIF2S1, EIF4EBP1, HSP90AB1, TP53, and HSPA8, which were mainly involved in the PI3K-AKT signaling pathway. SBVS of the seed molecule PTEN (PDB code: 1D5R) predicted top hits compounds that may serve as potential inhibitors of PTEN, of which the compound ZINC4235331 had the lowest binding affinity of -10 kcal/mol. The significance of screened hub genes and potential inhibitors involved in the process of LT provides novel therapeutic strategies for improving the outcomes of LT recipients during surgery.
期刊介绍:
MCP - Advancing biology through–omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.