胰腺炎免疫细胞特征和诊断基因标记的整合:治疗靶点和预测诊断的综合研究

IF 3.7 2区 医学 Q2 GENETICS & HEREDITY
Qianyu Xie, Birong Liu, Xiao Yu, Xiang Wei, Qiangsheng Xiao
{"title":"胰腺炎免疫细胞特征和诊断基因标记的整合:治疗靶点和预测诊断的综合研究","authors":"Qianyu Xie,&nbsp;Birong Liu,&nbsp;Xiao Yu,&nbsp;Xiang Wei,&nbsp;Qiangsheng Xiao","doi":"10.1155/humu/7694723","DOIUrl":null,"url":null,"abstract":"<p>Pancreatitis is a severe and increasingly prevalent disease that affects the digestive system. Early detection and accurate diagnosis of this condition are crucial for reducing mortality rates and improving patient outcomes. Therefore, the development of novel diagnostic markers is essential for enhancing clinical management and advancing the understanding of pancreatitis. The initial phase involved applying the ssGSEA method to extract hypoxia scores from these samples. Subsequently, a thorough differential expression analysis was performed, complemented by functional assessments and various machine learning techniques designed to pinpoint critical diagnostic genes relevant to pancreatitis. From this, a robust diagnostic model was constructed and validated using a series of machine learning strategies. To further validate our results, molecular docking studies were conducted to determine the binding affinities between the identified markers and standard medications such as omeprazole and lansoprazole. Additionally, the ssGSEA methodology was leveraged to compute immune cell scores within the pancreatitis samples, thus enriching the analysis of the relationships between significant diagnostic genes and various immune cell types. Finally, the experiments of ELISA and qRT-PCR were used to verify the expression of key target genes. Through WGCNA, we identified a total of 50 genes associated with hypoxic conditions within the pancreatitis samples. Further investigations, including differential expression analysis and machine learning techniques, revealed six significant diagnostic markers for pancreatitis: RAP1GDS1, TOP2A, ADK, POLL, CD44, and CD4. The diagnostic model we developed exhibited a high accuracy level in predicting pancreatitis onset, while molecular docking analyses indicated that these six key diagnostic genes hold promise as drug targets. Moreover, the ssGSEA algorithm confirmed the relationships between these diagnostic markers and a range of immune cell populations. Ultimately, the expression levels of the identified key genes were rigorously validated through experimental techniques, reinforcing the credibility of our findings.</p>","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"2025 1","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/humu/7694723","citationCount":"0","resultStr":"{\"title\":\"Integration of Immune Cell Signatures and Diagnostic Gene Markers in Pancreatitis: A Comprehensive Study on Therapeutic Targets and Predictive Diagnosis\",\"authors\":\"Qianyu Xie,&nbsp;Birong Liu,&nbsp;Xiao Yu,&nbsp;Xiang Wei,&nbsp;Qiangsheng Xiao\",\"doi\":\"10.1155/humu/7694723\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Pancreatitis is a severe and increasingly prevalent disease that affects the digestive system. Early detection and accurate diagnosis of this condition are crucial for reducing mortality rates and improving patient outcomes. Therefore, the development of novel diagnostic markers is essential for enhancing clinical management and advancing the understanding of pancreatitis. The initial phase involved applying the ssGSEA method to extract hypoxia scores from these samples. Subsequently, a thorough differential expression analysis was performed, complemented by functional assessments and various machine learning techniques designed to pinpoint critical diagnostic genes relevant to pancreatitis. From this, a robust diagnostic model was constructed and validated using a series of machine learning strategies. To further validate our results, molecular docking studies were conducted to determine the binding affinities between the identified markers and standard medications such as omeprazole and lansoprazole. Additionally, the ssGSEA methodology was leveraged to compute immune cell scores within the pancreatitis samples, thus enriching the analysis of the relationships between significant diagnostic genes and various immune cell types. Finally, the experiments of ELISA and qRT-PCR were used to verify the expression of key target genes. Through WGCNA, we identified a total of 50 genes associated with hypoxic conditions within the pancreatitis samples. Further investigations, including differential expression analysis and machine learning techniques, revealed six significant diagnostic markers for pancreatitis: RAP1GDS1, TOP2A, ADK, POLL, CD44, and CD4. The diagnostic model we developed exhibited a high accuracy level in predicting pancreatitis onset, while molecular docking analyses indicated that these six key diagnostic genes hold promise as drug targets. Moreover, the ssGSEA algorithm confirmed the relationships between these diagnostic markers and a range of immune cell populations. Ultimately, the expression levels of the identified key genes were rigorously validated through experimental techniques, reinforcing the credibility of our findings.</p>\",\"PeriodicalId\":13061,\"journal\":{\"name\":\"Human Mutation\",\"volume\":\"2025 1\",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1155/humu/7694723\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Human Mutation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1155/humu/7694723\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Mutation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/humu/7694723","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

摘要

胰腺炎是一种影响消化系统的严重且日益流行的疾病。这种疾病的早期发现和准确诊断对于降低死亡率和改善患者预后至关重要。因此,开发新的诊断标志物对于加强临床管理和提高对胰腺炎的认识至关重要。初始阶段涉及应用ssGSEA方法从这些样本中提取缺氧评分。随后,进行了彻底的差异表达分析,辅以功能评估和各种机器学习技术,旨在确定与胰腺炎相关的关键诊断基因。在此基础上,构建了一个鲁棒的诊断模型,并使用一系列机器学习策略进行了验证。为了进一步验证我们的结果,我们进行了分子对接研究,以确定鉴定的标记物与标准药物(如奥美拉唑和兰索拉唑)之间的结合亲和力。此外,ssGSEA方法被用于计算胰腺炎样本中的免疫细胞评分,从而丰富了重要诊断基因与各种免疫细胞类型之间关系的分析。最后通过ELISA和qRT-PCR实验验证关键靶基因的表达。通过WGCNA,我们在胰腺炎样本中共鉴定了50个与缺氧条件相关的基因。进一步的研究,包括差异表达分析和机器学习技术,揭示了胰腺炎的六个重要诊断标志物:RAP1GDS1, TOP2A, ADK, POLL, CD44和CD4。我们开发的诊断模型在预测胰腺炎发病方面显示出较高的准确性,而分子对接分析表明,这六个关键的诊断基因有望成为药物靶点。此外,ssGSEA算法证实了这些诊断标记物与一系列免疫细胞群之间的关系。最终,通过实验技术严格验证了鉴定出的关键基因的表达水平,加强了我们研究结果的可信度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Integration of Immune Cell Signatures and Diagnostic Gene Markers in Pancreatitis: A Comprehensive Study on Therapeutic Targets and Predictive Diagnosis

Integration of Immune Cell Signatures and Diagnostic Gene Markers in Pancreatitis: A Comprehensive Study on Therapeutic Targets and Predictive Diagnosis

Pancreatitis is a severe and increasingly prevalent disease that affects the digestive system. Early detection and accurate diagnosis of this condition are crucial for reducing mortality rates and improving patient outcomes. Therefore, the development of novel diagnostic markers is essential for enhancing clinical management and advancing the understanding of pancreatitis. The initial phase involved applying the ssGSEA method to extract hypoxia scores from these samples. Subsequently, a thorough differential expression analysis was performed, complemented by functional assessments and various machine learning techniques designed to pinpoint critical diagnostic genes relevant to pancreatitis. From this, a robust diagnostic model was constructed and validated using a series of machine learning strategies. To further validate our results, molecular docking studies were conducted to determine the binding affinities between the identified markers and standard medications such as omeprazole and lansoprazole. Additionally, the ssGSEA methodology was leveraged to compute immune cell scores within the pancreatitis samples, thus enriching the analysis of the relationships between significant diagnostic genes and various immune cell types. Finally, the experiments of ELISA and qRT-PCR were used to verify the expression of key target genes. Through WGCNA, we identified a total of 50 genes associated with hypoxic conditions within the pancreatitis samples. Further investigations, including differential expression analysis and machine learning techniques, revealed six significant diagnostic markers for pancreatitis: RAP1GDS1, TOP2A, ADK, POLL, CD44, and CD4. The diagnostic model we developed exhibited a high accuracy level in predicting pancreatitis onset, while molecular docking analyses indicated that these six key diagnostic genes hold promise as drug targets. Moreover, the ssGSEA algorithm confirmed the relationships between these diagnostic markers and a range of immune cell populations. Ultimately, the expression levels of the identified key genes were rigorously validated through experimental techniques, reinforcing the credibility of our findings.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Human Mutation
Human Mutation 医学-遗传学
CiteScore
8.40
自引率
5.10%
发文量
190
审稿时长
2 months
期刊介绍: Human Mutation is a peer-reviewed journal that offers publication of original Research Articles, Methods, Mutation Updates, Reviews, Database Articles, Rapid Communications, and Letters on broad aspects of mutation research in humans. Reports of novel DNA variations and their phenotypic consequences, reports of SNPs demonstrated as valuable for genomic analysis, descriptions of new molecular detection methods, and novel approaches to clinical diagnosis are welcomed. Novel reports of gene organization at the genomic level, reported in the context of mutation investigation, may be considered. The journal provides a unique forum for the exchange of ideas, methods, and applications of interest to molecular, human, and medical geneticists in academic, industrial, and clinical research settings worldwide.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信