Development of stemness-related signature to optimize prognosis prediction and identify XMD8-85 as a novel therapeutic compound for glioma

Cellular Signalling, Journal Year: 2024, Volume and Issue: 120, P. 111231 - 111231

Published: May 18, 2024

Language: Английский

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Toden-E: Topology-Based and Density-Based Ensembled Clustering for the Development of Super-PAG in Functional Genomics using PAG Network and LLM

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Abstract The integrative analysis of gene sets, networks, and pathways is pivotal for deciphering omics data in translational biomedical research. To significantly increase coverage enhance the utility pathways, annotated lists, signatures from diverse sources, we introduced (PAGs) enriched with metadata to represent biological functions. Furthermore, established PAG-PAG networks by leveraging member similarity regulations. However, practice, high functional descriptions or membership often leads redundant PAGs, hindering interpretation a fuzzy PAG list. In this study, developed todenE (topology-based density-based ensemble) clustering, pioneering integrating topology-based clustering methods detect communities network Large Language Models (LLM). computational genomics annotation, genes can be grouped/clustered through relationships functions via guilt association. Similarly, PAGs grouped into higher-level clusters, forming concise representations called Super-PAGs. TodenE captures encapsulates information LLM, characterizing network-based synthetic data, metric Disparity Index (DI), measuring connectivity neighbors gauge clusterability. We compared multiple algorithms identify best method generating performance-driven clusters. non-simulated (Gene Ontology), transfer learning formed language-based embedding. utilizes embedding together generate putative Super-PAGs superior performance semantic inclusiveness.

Language: Английский

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Identified RP2 as a prognostic biomarker for glioma, facilitating glioma pathogenesis mainly via regulating tumor immunity

Aging, Journal Year: 2023, Volume and Issue: 15(16), P. 8155 - 8184

Published: Aug. 18, 2023

Glioma is the most common primary intracranial tumor in central nervous system, with a high degree of malignancy and poor prognosis, easy to recur, difficult cure. The mutation Retinitis Pigmentosa 2 (RP2) can cause retinitis pigmentosa, it prognostic factor osteosarcoma, however, its role glioma remains unclear. Based on data from TCGA GTEx, we identified RP2 as related gene for by WGCNA, used series bioinformatics analyses including LinkedOmics, GSCA, CTD, so on, explore expression biological functions involved in. results showed that was highly expressed glioma, overexpression could lead prognosis. In addition, enrichment analysis correlated cell proliferation immune response. And then, found significant Macrophages among cells. Furthermore, our experiments have confirmed promote development secreting or influencing secretion some cytokines. Moreover, investigated influence immunotherapy m6A modification glioma. Ultimately, determined an independent mainly closely

Language: Английский

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A prognostic gene signature based on focal adhesion related genes for gliomas and identification of the role of RAP1B in glioma progression

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 18, 2023

Abstract Background The most common malignant primary brain tumor in adults is the gliomas, characterized by extremely variable overall survival (OS) for patients. Although it has been found that focal adhesion genes are associated with clinical prognosis glioma patients, this marker rarely used clinically. Methods We systematically mRNA expression of related gliomas and explored their signature based on 938 samples from TCGA dataset CGGA dataset. Glioma were clustered using an unsupervised clustering method. Subsequently, prognosis-associated genes, gene (FARGS) was constructed least absolute shrinkage selection operator (LASSO) Cox regression. Additionally, multiple bioinformatics methods to examine value FARGS predicting patient outcomes, features, oncogenic pathways, immune microenvironment drug response. Furthermore, vitro vivo experiments conducted validate role RAP1B U87 cells. Results According LASSO regression analysis, a 9-FARG be strongly linked OS high-risk low-risk score pattern. tightly molecular biomarkers, including IDH wild-type, unmethylated MGMTp, non-codeletion 1p19q. group exhibited enrichment biological pathways. Interestingly, results presented strong association therapeutic response immunosuppressive infiltrations M2-type macrophages, MDSCs Tregs, elevated immunosuppressors’ expression. Lastly, cells also functionally confirmed. Conclusions In conclusion, we reported novel promising prediction as well confirmation RAP1B's role.

Language: Английский

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