Sinan Eyuboglu , Semih Alpsoy , Vladimir N. Uversky , Orkid Coskuner-Weber
{"title":"胰腺导管腺癌分子图谱中的关键基因和通路:一项生物信息学和机器学习研究。","authors":"Sinan Eyuboglu , Semih Alpsoy , Vladimir N. Uversky , Orkid Coskuner-Weber","doi":"10.1016/j.compbiolchem.2024.108268","DOIUrl":null,"url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is recognized for its aggressive nature, dismal prognosis, and a notably low five-year survival rate, underscoring the critical need for early detection methods and more effective therapeutic approaches. This research rigorously investigates the molecular mechanisms underlying PDAC, with a focus on the identification of pivotal genes and pathways that may hold therapeutic relevance and prognostic value. Through the construction of a protein-protein interaction (PPI) network and the examination of differentially expressed genes (DEGs), the study uncovers key hub genes such as CDK1, KIF11, and BUB1, demonstrating their substantial role in the pathogenesis of PDAC. Notably, the dysregulation of these genes is consistent across a spectrum of cancers, positing them as potential targets for wide-ranging cancer therapeutics. This study also brings to the fore significant genes encoding intrinsically disordered proteins, in particular GPRC5A and KRT7, unveiling promising new pathways for therapeutic intervention. Advanced machine learning techniques were harnessed to classify PDAC patients with high accuracy, utilizing the key genetic markers as a dataset. The Support Vector Machine (SVM) model leveraged the hub genes to achieve a sensitivity of 91 % and a specificity of 85 %, while the RandomForest model notched a sensitivity of 91 % and specificity of 92.5 %. Crucially, when the identified genes were cross-referenced with TCGA-PAAD clinical datasets, a tangible correlation with patient survival rates was discovered, reinforcing the potential of these genes as prognostic biomarkers and their viability as targets for therapeutic intervention. This study's findings serve as a potent testament to the value of molecular analysis in enhancing the understanding of PDAC and in advancing the pursuit for more effective diagnostic and treatment strategies.</div></div>","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":"113 ","pages":"Article 108268"},"PeriodicalIF":2.6000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Key genes and pathways in the molecular landscape of pancreatic ductal adenocarcinoma: A bioinformatics and machine learning study\",\"authors\":\"Sinan Eyuboglu , Semih Alpsoy , Vladimir N. Uversky , Orkid Coskuner-Weber\",\"doi\":\"10.1016/j.compbiolchem.2024.108268\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is recognized for its aggressive nature, dismal prognosis, and a notably low five-year survival rate, underscoring the critical need for early detection methods and more effective therapeutic approaches. This research rigorously investigates the molecular mechanisms underlying PDAC, with a focus on the identification of pivotal genes and pathways that may hold therapeutic relevance and prognostic value. Through the construction of a protein-protein interaction (PPI) network and the examination of differentially expressed genes (DEGs), the study uncovers key hub genes such as CDK1, KIF11, and BUB1, demonstrating their substantial role in the pathogenesis of PDAC. Notably, the dysregulation of these genes is consistent across a spectrum of cancers, positing them as potential targets for wide-ranging cancer therapeutics. This study also brings to the fore significant genes encoding intrinsically disordered proteins, in particular GPRC5A and KRT7, unveiling promising new pathways for therapeutic intervention. Advanced machine learning techniques were harnessed to classify PDAC patients with high accuracy, utilizing the key genetic markers as a dataset. The Support Vector Machine (SVM) model leveraged the hub genes to achieve a sensitivity of 91 % and a specificity of 85 %, while the RandomForest model notched a sensitivity of 91 % and specificity of 92.5 %. Crucially, when the identified genes were cross-referenced with TCGA-PAAD clinical datasets, a tangible correlation with patient survival rates was discovered, reinforcing the potential of these genes as prognostic biomarkers and their viability as targets for therapeutic intervention. This study's findings serve as a potent testament to the value of molecular analysis in enhancing the understanding of PDAC and in advancing the pursuit for more effective diagnostic and treatment strategies.</div></div>\",\"PeriodicalId\":10616,\"journal\":{\"name\":\"Computational Biology and Chemistry\",\"volume\":\"113 \",\"pages\":\"Article 108268\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-10-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Computational Biology and Chemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1476927124002561\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Computational Biology and Chemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1476927124002561","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
Key genes and pathways in the molecular landscape of pancreatic ductal adenocarcinoma: A bioinformatics and machine learning study
Pancreatic ductal adenocarcinoma (PDAC) is recognized for its aggressive nature, dismal prognosis, and a notably low five-year survival rate, underscoring the critical need for early detection methods and more effective therapeutic approaches. This research rigorously investigates the molecular mechanisms underlying PDAC, with a focus on the identification of pivotal genes and pathways that may hold therapeutic relevance and prognostic value. Through the construction of a protein-protein interaction (PPI) network and the examination of differentially expressed genes (DEGs), the study uncovers key hub genes such as CDK1, KIF11, and BUB1, demonstrating their substantial role in the pathogenesis of PDAC. Notably, the dysregulation of these genes is consistent across a spectrum of cancers, positing them as potential targets for wide-ranging cancer therapeutics. This study also brings to the fore significant genes encoding intrinsically disordered proteins, in particular GPRC5A and KRT7, unveiling promising new pathways for therapeutic intervention. Advanced machine learning techniques were harnessed to classify PDAC patients with high accuracy, utilizing the key genetic markers as a dataset. The Support Vector Machine (SVM) model leveraged the hub genes to achieve a sensitivity of 91 % and a specificity of 85 %, while the RandomForest model notched a sensitivity of 91 % and specificity of 92.5 %. Crucially, when the identified genes were cross-referenced with TCGA-PAAD clinical datasets, a tangible correlation with patient survival rates was discovered, reinforcing the potential of these genes as prognostic biomarkers and their viability as targets for therapeutic intervention. This study's findings serve as a potent testament to the value of molecular analysis in enhancing the understanding of PDAC and in advancing the pursuit for more effective diagnostic and treatment strategies.
期刊介绍:
Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered.
Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered.
Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.