Normal view
-
cs.AI, q-bio.NC updates on arXiv.org
-
AI Deception: Risks, Dynamics, and Controls
arXiv:2511.22619v2 Announce Type: replace Abstract: As intelligence increases, so does its shadow. AI deception, in which systems induce false beliefs to secure self-beneficial outcomes, has evolved from a speculative concern to an empirically demonstrated risk across language models, AI agents, and emerging frontier systems. This project provides a comprehensive and up-to-date overview of the AI deception field, covering its core concepts, methodologies, genesis, and potential mitigations. Fir
-
(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
-
Unraveling the role of GPCR signaling in metabolic reprogramming and immune microenvironment of lung adenocarcinoma: a multi-omics study with experimental validation
Front Immunol. 2025 Jun 6;16:1606125. doi: 10.3389/fimmu.2025.1606125. eCollection 2025.ABSTRACTBACKGROUND: Lung adenocarcinoma (LUAD) is characterized by metabolic and immune heterogeneity, driving tumor progression and therapy resistance. While G protein-coupled receptors (GPCR) signaling is known to regulate metabolism and immunity in cancers, its role in LUAD remains poorly defined. This study explores the influence of GPCR signaling on LUAD metabolism and immune landscape.METHODS: We perfor
Unraveling the role of GPCR signaling in metabolic reprogramming and immune microenvironment of lung adenocarcinoma: a multi-omics study with experimental validation
Front Immunol. 2025 Jun 6;16:1606125. doi: 10.3389/fimmu.2025.1606125. eCollection 2025.
ABSTRACT
BACKGROUND: Lung adenocarcinoma (LUAD) is characterized by metabolic and immune heterogeneity, driving tumor progression and therapy resistance. While G protein-coupled receptors (GPCR) signaling is known to regulate metabolism and immunity in cancers, its role in LUAD remains poorly defined. This study explores the influence of GPCR signaling on LUAD metabolism and immune landscape.
METHODS: We performed non-negative matrix factorization (NMF) clustering of GPCR signaling genes in TCGA-LUAD cohort to identify distinct molecular subgroups. A prognostic model was developed based on GPCR signaling genes using least absolute shrinkage and selection operator (LASSO) analysis and Cox regression. Differentially expressed genes were analyzed for metabolic pathway enrichment and immune infiltration. In addition, key genes within GPCR signaling were identified and validated through functional assays.
RESULTS: NMF clustering based on GPCR signaling identified three subgroups in LUAD, with cluster 3 exhibiting poorer overall survival and significant enrichment in multiple prognostic associated metabolism pathways including purine, pyrimidine, glyoxylate and dicarboxylate metabolism. Then, we developed a GPCRscore prognostic model and validated across multiple cohorts, which effectively stratified LUAD patients into distinct risk groups. High-risk LUAD patients had an immunosuppressive microenvironment and activated metabolic reprogramming. ADM was identified as a key gene in the high-risk group, correlating with tumor stage, immune suppression, and resistance to immunotherapy. Clinically, ADM was highly expressed in tumor tissues and shows elevated concentrations in the peripheral blood of patients with advanced-stage LUAD. Subsequently, we demonstrated that knock-down of ADM in LUAD cells impaired their proliferation, migration, and invasion, while also reducing the angiogenic potential of endothelial cells in vitro. Adrenomedullin promoted LUAD progression in a murine metastasis model. Further, adrenomedullin inhibited CD8+ T cells proliferation, induced exhaustion, and impaired cytotoxic function. Finally, drug sensitivity and cell viability analysis showed LUAD patients with high levels of ADM exhibited sensitivity to the treatment of Staurosporine and Dasatinib.
CONCLUSIONS: In summary, this study reveals the pivotal role of GPCR signaling particularly mediated by ADM in orchestrating metabolic reprogramming and immune modulation in LUAD. ADM emerges as a potential predictive biomarker and therapeutic target, offering valuable implications for optimizing strategies.
PMID:40547013 | PMC:PMC12179119 | DOI:10.3389/fimmu.2025.1606125
-
(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
-
A statistical framework for multi-trait rare variant analysis in large-scale whole-genome sequencing studies
Nat Comput Sci. 2025 Feb 7. doi: 10.1038/s43588-024-00764-8. Online ahead of print.ABSTRACTLarge-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limi
A statistical framework for multi-trait rare variant analysis in large-scale whole-genome sequencing studies
Nat Comput Sci. 2025 Feb 7. doi: 10.1038/s43588-024-00764-8. Online ahead of print.
ABSTRACT
Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally scalable analytical pipeline for functionally informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits in 61,838 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered and replicated new associations with lipid traits missed by single-trait analysis.
PMID:39920506 | DOI:10.1038/s43588-024-00764-8