Long non-coding RNAs (lncRNAs) have emerged as significant contributors to the regulation of various biological processes, and their dysregulation has been linked to a variety of human disorders. Accurate prediction of potential correlations between lncRNAs and diseases is crucial for advancing disease diagnostics and treatment procedures. The authors introduced a novel computational method, iGATTLDA, for the prediction of lncRNA-disease associations. The model utilised lncRNA and disease similarity matrices, with known associations represented in an adjacency matrix. A heterogeneous network was constructed, dissecting lncRNAs and diseases as nodes and their associations as edges. The Graph Attention Network (GAT) is employed to process initial features and corresponding adjacency information. GAT identified significant neighbouring nodes in the network, capturing intricate relationships between lncRNAs and diseases, and generating new feature representations. Subsequently, the transformer captures global dependencies and interactions across the entire sequence of features produced by the GAT. Consequently, iGATTLDA successfully captures complex relationships and interactions that conventional approaches may overlook. In evaluating iGATTLDA, it attained an area under the receiver operating characteristic (ROC) curve (AUC) of 0.95 and an area under the precision recall curve (AUPRC) of 0.96 with a two-layer multilayer perceptron (MLP) classifier. These results were notably higher compared to the majority of previously proposed models, further substantiating the model's efficiency in predicting potential lncRNA-disease associations by incorporating both local and global interactions. The implementation details can be obtained from https://github.com/momanyibiffon/iGATTLDA.
{"title":"iGATTLDA: Integrative graph attention and transformer-based model for predicting lncRNA-Disease associations.","authors":"Biffon Manyura Momanyi, Sebu Aboma Temesgen, Tian-Yu Wang, Hui Gao, Ru Gao, Hua Tang, Li-Xia Tang","doi":"10.1049/syb2.12098","DOIUrl":"https://doi.org/10.1049/syb2.12098","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) have emerged as significant contributors to the regulation of various biological processes, and their dysregulation has been linked to a variety of human disorders. Accurate prediction of potential correlations between lncRNAs and diseases is crucial for advancing disease diagnostics and treatment procedures. The authors introduced a novel computational method, iGATTLDA, for the prediction of lncRNA-disease associations. The model utilised lncRNA and disease similarity matrices, with known associations represented in an adjacency matrix. A heterogeneous network was constructed, dissecting lncRNAs and diseases as nodes and their associations as edges. The Graph Attention Network (GAT) is employed to process initial features and corresponding adjacency information. GAT identified significant neighbouring nodes in the network, capturing intricate relationships between lncRNAs and diseases, and generating new feature representations. Subsequently, the transformer captures global dependencies and interactions across the entire sequence of features produced by the GAT. Consequently, iGATTLDA successfully captures complex relationships and interactions that conventional approaches may overlook. In evaluating iGATTLDA, it attained an area under the receiver operating characteristic (ROC) curve (AUC) of 0.95 and an area under the precision recall curve (AUPRC) of 0.96 with a two-layer multilayer perceptron (MLP) classifier. These results were notably higher compared to the majority of previously proposed models, further substantiating the model's efficiency in predicting potential lncRNA-disease associations by incorporating both local and global interactions. The implementation details can be obtained from https://github.com/momanyibiffon/iGATTLDA.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jian Wang, Tao Guo, Yuanyuan Mi, Xiangyu Meng, Shuang Xu, Feng Dai, Chengwen Sun, Yi Huang, Jun Wang, Lijie Zhu, Jianquan Hou, Sheng Wu
For the multistage progression of prostate cancer (PCa) and resistance to immunotherapy, tumour-associated macrophage is an essential contributor. Although immunotherapy is an important and promising treatment modality for cancer, most patients with PCa are not responsive towards it. In addition to exploring new therapeutic targets, it is imperative to identify highly immunotherapy-sensitive individuals. This research aimed to establish a signature risk model, which derived from the macrophage, to assess immunotherapeutic responses and predict prognosis. Data from the UCSC-XENA, GEO and TISCH databases were extracted for analysis. Based on both single-cell datasets and bulk transcriptome profiles, a macrophage-related score (MRS) consisting of the 10-gene panel was constructed using the gene set variation analysis. MRS was highly correlated with hypoxia, angiogenesis, and epithelial-mesenchymal transition, suggesting its potential as a risk indicator. Moreover, poor immunotherapy responses and worse prognostic performance were observed in the high-MRS group of various immunotherapy cohorts. Additionally, APOE, one of the constituent genes of the MRS, affected the polarisation of macrophages. In particular, the reduced level of M2 macrophage and tumour progression suppression were observed in PCa xenografts which implanted in Apolipoprotein E-knockout mice. The constructed MRS has the potential as a robust prognostic prediction tool, and can aid in the treatment selection of PCa, especially immunotherapy options.
{"title":"A tumour-associated macrophage-based signature for deciphering prognosis and immunotherapy response in prostate cancer.","authors":"Jian Wang, Tao Guo, Yuanyuan Mi, Xiangyu Meng, Shuang Xu, Feng Dai, Chengwen Sun, Yi Huang, Jun Wang, Lijie Zhu, Jianquan Hou, Sheng Wu","doi":"10.1049/syb2.12097","DOIUrl":"https://doi.org/10.1049/syb2.12097","url":null,"abstract":"<p><p>For the multistage progression of prostate cancer (PCa) and resistance to immunotherapy, tumour-associated macrophage is an essential contributor. Although immunotherapy is an important and promising treatment modality for cancer, most patients with PCa are not responsive towards it. In addition to exploring new therapeutic targets, it is imperative to identify highly immunotherapy-sensitive individuals. This research aimed to establish a signature risk model, which derived from the macrophage, to assess immunotherapeutic responses and predict prognosis. Data from the UCSC-XENA, GEO and TISCH databases were extracted for analysis. Based on both single-cell datasets and bulk transcriptome profiles, a macrophage-related score (MRS) consisting of the 10-gene panel was constructed using the gene set variation analysis. MRS was highly correlated with hypoxia, angiogenesis, and epithelial-mesenchymal transition, suggesting its potential as a risk indicator. Moreover, poor immunotherapy responses and worse prognostic performance were observed in the high-MRS group of various immunotherapy cohorts. Additionally, APOE, one of the constituent genes of the MRS, affected the polarisation of macrophages. In particular, the reduced level of M2 macrophage and tumour progression suppression were observed in PCa xenografts which implanted in Apolipoprotein E-knockout mice. The constructed MRS has the potential as a robust prognostic prediction tool, and can aid in the treatment selection of PCa, especially immunotherapy options.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongjie Gao, Chen Ding, Mengmeng Chang, Zhiyi Lu, Ding Li, Dan Bi, Fengyin Sun
EMT dysfunction is a dominant mechanisms of hypospadias. Thus, identification of EMT-related lncRNAs based on transcriptome sequencing data of hypospadias might provide novel molecular markers and therapeutic targets for hypospadias. First, the microarray data related to hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the differentially expressed lncRNAs and messenger RNAs (mRNAs) related to EMT were screened to construct lncRNA-mRNA co-expression interaction pairs. In addition, the microRNA (miRNA) prediction analysis was performed through bioinformatics methods to construct a ceRNA network. Moreover, function prediction and function enrichment and pathway analyses were also performed. Finally, the core EMT-related lncRNAs were verified based on mRNA expression changes and cell functions. A total of 6 EMT-related lncRNAs were identified and 123 mRNA-lncRNA co-expression interaction pairs were screened in this study. Additionally, a ceRNA regulatory network comprising 17 mRNAs, 4 lncRNAs, and 28 miRNAs was constructed based on the prediction of hypospadias-related miRNAs. The validation results of the dataset GSE121712 revealed that only BEX1 was positively correlated with the expression of the lncRNA GNAS-AS1 (r = 0.874, P < 0.01), both of which had high expression. The cell experiment results demonstrated that interfering with the expression of GNAS-AS1 significantly promoted the proliferation, migration, and EMT of cells. Importantly, it was confirmed that GNAS-AS1 can serve as a ceRNA and play an important role in the EMT of hypospadias. Hence, it may be considered as a potential target in the treatment of this disease.
{"title":"Identification and analysis of epithelial-mesenchymal transition-related key long non-coding RNAs in hypospadias","authors":"Hongjie Gao, Chen Ding, Mengmeng Chang, Zhiyi Lu, Ding Li, Dan Bi, Fengyin Sun","doi":"10.1049/syb2.12096","DOIUrl":"10.1049/syb2.12096","url":null,"abstract":"<p>EMT dysfunction is a dominant mechanisms of hypospadias. Thus, identification of EMT-related lncRNAs based on transcriptome sequencing data of hypospadias might provide novel molecular markers and therapeutic targets for hypospadias. First, the microarray data related to hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the differentially expressed lncRNAs and messenger RNAs (mRNAs) related to EMT were screened to construct lncRNA-mRNA co-expression interaction pairs. In addition, the microRNA (miRNA) prediction analysis was performed through bioinformatics methods to construct a ceRNA network. Moreover, function prediction and function enrichment and pathway analyses were also performed. Finally, the core EMT-related lncRNAs were verified based on mRNA expression changes and cell functions. A total of 6 EMT-related lncRNAs were identified and 123 mRNA-lncRNA co-expression interaction pairs were screened in this study. Additionally, a ceRNA regulatory network comprising 17 mRNAs, 4 lncRNAs, and 28 miRNAs was constructed based on the prediction of hypospadias-related miRNAs. The validation results of the dataset GSE121712 revealed that only BEX1 was positively correlated with the expression of the lncRNA GNAS-AS1 (r = 0.874, <i>P</i> < 0.01), both of which had high expression. The cell experiment results demonstrated that interfering with the expression of GNAS-AS1 significantly promoted the proliferation, migration, and EMT of cells. Importantly, it was confirmed that GNAS-AS1 can serve as a ceRNA and play an important role in the EMT of hypospadias. Hence, it may be considered as a potential target in the treatment of this disease.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1049/syb2.12096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}