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Quantifying Individual Health Status from Multi-omics Data by Health State Manifold
Phenomics. 2025 Dec 15;5(5):469-486. doi: 10.1007/s43657-024-00188-4. eCollection 2025 Oct.
ABSTRACT
Quantifying individual health status from increasingly accumulated omics data is essential for both early prevention and intervention of diseases, which attracts great attention from communities of biology and medicine. Most of the existing approaches mainly classify individuals into different catalogues or classes based on phenotypes and biomarkers. However, an individual's health status from a dynamical systems viewpoint can be viewed as a non-equilibrium steady state, which can generally be characterized by two key features, i.e. (1) homeostatic potential that represents the ability of homeostatic resilience to withstand perturbations or maintain functions at the current state/phenotype of this individual and (2) phenotypic potential that represents the state/phenotype of the individual on the whole process from health to disease. Here, we proposed a health state manifold (HSM) method derived from dynamic network biomarker method and diffusion map theory to quantify individual health status with the characterization of such two features in a robust and accurate manner based on multi-omics data. To verify our method, HSM method was applied to the quantification of diabetes mellitus (rat subjects) and the Roux-en-Y Gastric Bypass (human subjects) for both disease progression process and recovery process, which demonstrated its effectiveness and potential for personalized medicine and preventive medicine.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-024-00188-4.
PMID:41659741 | PMC:PMC12881232 | DOI:10.1007/s43657-024-00188-4
Spatial Multi-omics Analyses Reveal Diabetes Promotes Pancreatic Cancer Progression by Stimulating Cholesterol-Induced Neutrophil Extracellular Trap Formation
Cancer Res. 2026 Feb 9. doi: 10.1158/0008-5472.CAN-25-2854. Online ahead of print.
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) patients with diabetes mellitus (DM) exhibit poor clinical outcomes. Metabolic reprogramming of both cancer cells and immune compartments plays a crucial role in shaping the anti-tumor immune response in PDAC. DM-induced metabolic alteration may disrupt the intricate crosstalk between immune cells and tumor-associated immune factors, profoundly influencing PDAC progression. Here, we performed an integrated, spatially resolved multi-omics study to investigate DM-associated, cell-specific metabolic remodeling within the PDAC tumor microenvironment. DM influenced interactions between tumor cells and immune cells, which accelerated PDAC growth in both humans and mice. PDAC patients with DM exhibited higher tumor-stage, poorer differentiation, and worse outcomes. Spatial metabolic and transcriptional profiling revealed that SREBP2-dependent cholesterol biosynthesis exacerbated PDAC progression. Increased cholesterol biosynthesis promoted neutrophil recruitment and accelerated formation of neutrophil extracellular traps (NETs) by stimulating the CXCL1-CXCR1/CXCR2 signaling axis, ultimately promoting PDAC growth. Inhibition of SREBP2, pharmacological blockade of CXCL1, or perturbation of NETs markedly reduced PDAC growth in diabetic mouse models. Together, these multi-omics analyses and follow-up mechanistic studies constitute an integrated approach that elucidates a metabolic mechanism by which diabetes promotes PDAC development by remodeling the tumor immune microenvironment and highlights a potential therapeutic strategy for PDAC with DM.
PMID:41661642 | DOI:10.1158/0008-5472.CAN-25-2854
The challenge of generating and evolving real-life like synthetic test data without accessing real-world raw data -- a Systematic Review
Yunjue Agent Tech Report: A Fully Reproducible, Zero-Start In-Situ Self-Evolving Agent System for Open-Ended Tasks
Data-Centric Interpretability for LLM-based Multi-Agent Reinforcement Learning
Exploring AI-Augmented Sensemaking of Patient-Generated Health Data: A Mixed-Method Study with Healthcare Professionals in Cardiac Risk Reduction
Reliability of LLMs as medical assistants for the general public: a randomized preregistered study
Nature Medicine, Published online: 09 February 2026; doi:10.1038/s41591-025-04074-y
In a randomized controlled study involving 1,298 participants from a general sample, performance of humans when assisted by a large language model (LLM) was sensibly inferior to that of the LLM alone when assessing ten medical scenarios leading to disease identification and recommendations for treatment.Sensitive detection of cancer antigens enabled by user-defined peptide libraries
Nature Biotechnology, Published online: 09 February 2026; doi:10.1038/s41587-026-03003-9
Insights into regulatory T cell biology are accelerating therapeutic innovation in cancer immunotherapy, autoimmune diseases and transplant rejection.Integrating liquid biopsies in non-small cell lung cancer diagnosis and management: opportunities and challenges
Expert Rev Anticancer Ther. 2026 Feb 15:1-12. doi: 10.1080/14737140.2026.2630026. Online ahead of print.
ABSTRACT
INTRODUCTION: Liquid biopsy has emerged as an important approach to capture tumor-derived material from blood and other body fluids, offering a minimally invasive window into cancer biology. In non - small cell lung cancer (NSCLC), it enables comprehensive molecular profiling that informs patient management, from guiding therapy choices to monitoring disease status and assessing minimal residual disease (MRD).
AREAS COVERED: Its main advantages over tissue biopsy lie in being noninvasive, capable of reflecting tumor heterogeneity and real-time biological changes. These strengths allow liquid biopsy to be applied at different clinical timepoints, including diagnosis, treatment decision-making, evaluation during therapy, detection of resistance, and surveillance for recurrence. Although circulating tumor DNA (ctDNA) remains the most established analyte, the scope is broadening to include circulating RNAs, circulating tumor cells, exosomes, DNA methylation signatures, and tumor-educated platelets, each providing complementary insights. A literature search of PubMed, EMBASE, and Web of Science was conducted without restrictions, supplemented by screening reference lists and major oncology conference abstracts.
EXPERT OPINION: While significant progress has been made integrating liquid biopsies in NSCLC, challenges persist, encompassing issues of standardization, cost, and clinical integration.
PMID:41656166 | DOI:10.1080/14737140.2026.2630026
From Amphiphiles to mRNA platforms: emerging vaccination strategies for pancreatic cancer
Exp Hematol Oncol. 2026 Feb 7. doi: 10.1186/s40164-026-00755-7. Online ahead of print.
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest cancers, with limited surgical eligibility, modest chemotherapy benefit, and resistance to immune checkpoint blockade. Two recent vaccine platforms have shown encouraging results. Wainberg et al. demonstrated that the amphiphile vaccine ELI-002 efficiently traffics to lymph nodes via albumin binding and induced KRAS-specific T-cell responses in most patients, correlating with survival. In parallel, Sethna et al. reported that an individualized uridine-modified mRNA vaccine elicited durable, polyfunctional CD8⁺ T cells with long-term persistence, especially when combined with PD-1 blockade. Amphiphiles provide rapid and efficient priming, whereas mRNA vaccines broaden and sustain clonotypic diversity. A hybrid prime-boost strategy may synergize these complementary mechanisms, while advances in multi-omics and AI-driven neoantigen prediction pave the way for personalized designs. Together, these developments suggest that PDAC, long regarded as immunologically "cold," may become tractable to vaccination strategies. Importantly, these findings are based on early-phase clinical studies with limited patient numbers and should therefore be interpreted as preliminary clinical evidence requiring further studies.
PMID:41654971 | DOI:10.1186/s40164-026-00755-7
People process technology and operations framework for establishing AI governance in healthcare organizations
npj Digital Medicine, Published online: 07 February 2026; doi:10.1038/s41746-026-02419-6
People process technology and operations framework for establishing AI governance in healthcare organizationsThe Feasibility of Smartwatch Micro–Ecological Momentary Assessment for Tracking Eating Patterns of Malaysian Children and Adolescents in the South-East Asian Community Observatory Child Health Update 2020: Cross-Sectional Study
Digital Biomarkers for Precision Early Detection of Lung Cancer: Integrating AI-Driven Multi-Omics Into Clinical Pathways
Cancer Med. 2026 Feb;15(2):e71578. doi: 10.1002/cam4.71578.
ABSTRACT
BACKGROUND: Lung cancer remains the leading cause of cancer-related mortality worldwide, highlighting the urgent need for earlier detection within real-world screening and patient management pathways. Recent advances in multi-omics technologies have created new opportunities for identifying biomarkers associated with early-stage lung cancer, particularly in high-risk populations under clinical surveillance.
METHODS: This review systematically evaluates early diagnostic biomarkers across multiple omics layers, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiomics. It also summarises the application of artificial intelligence (AI), particularly machine learning and deep learning approaches, for integrating and analysing complex multi-omics datasets to support biomarker discovery and clinical decision-making.
RESULTS: Multi-omics strategies are accelerating the identification of molecular signatures relevant to early lung cancer detection. AI-driven methods enable the extraction of latent patterns from high-dimensional data, facilitating risk stratification, diagnostic refinement, histological subtyping and treatment planning. The review highlights the clinical utility of these biomarkers and their potential incorporation into screening algorithms, as well as the development of AI-based clinical decision support systems (CDSS) aligned with real-world clinical workflows. However, major barriers to clinical translation remain, including multi-centre data heterogeneity, limited model interpretability affecting clinical trust, regulatory and cost-effectiveness challenges and insufficient validation in prospective cohorts.
CONCLUSIONS: Emerging technologies, such as single-cell and spatial multi-omics, along with federated learning frameworks, offer promising solutions to bridge the gap between computational discovery and clinical implementation. The integration of AI and multi-omics approaches has the potential to advance risk-adapted and personalised early detection strategies for lung cancer.
PMID:41645653 | PMC:PMC12877424 | DOI:10.1002/cam4.71578
Tumor microbiome differences in early-onset versus average-onset pancreatic adenocarcinoma
ESMO Gastrointest Oncol. 2025 Jul 7;9:100194. doi: 10.1016/j.esmogo.2025.100194. eCollection 2025 Sep.
ABSTRACT
BACKGROUND: Compelling evidence supports the biomarker potential of microbiome in pancreatic adenocarcinoma. Given the knowledge gap on the characteristics and significance of microbiome in early-onset pancreatic ductal adenocarcinoma (eoPDAC, age <50 years), we aimed to evaluate microbiome profiles in resected specimens from individuals with eoPDAC and average-onset PDAC (aoPDAC, age >50 years).
MATERIALS AND METHODS: We carried out shotgun metagenomic sequencing in resected specimens from individuals with eoPDAC (n = 24) and aoPDAC (n = 20). Statistical tests included Wilcoxon test, permutational analysis of variance, multiomic classifier modeling, differential abundance analysis, and linear regression. All P values were adjusted for multiple testing and P < 0.05 was considered statistically significant.
RESULTS: We successfully sequenced several bacteria and fungi in the tumor specimens from 44 individuals with resected PDAC (24 eoPDAC and 20 aoPDAC). The alpha diversity of the bacterial microbiome was higher in eoPDAC tumor tissue compared with aoPDAC (P = 0.04). In contrast, the fungal mycobiome's alpha diversity was higher for aoPDAC tumor tissue (P = 0.02). Key organisms with differential abundance between tumor tissue from individuals with eoPDAC and aoPDAC included Bacillus, Candida, Collimonas, Cupriavidus, Enterobacter, Escherichia, Klebsiella, Malasseiza, Mucilaginibacter, Neisseria, and Sphingomonas. Higher bacterial diversity in tumor tissue was associated with better overall survival for individuals with eoPDAC (R = 0.26, P = 0.02).
CONCLUSIONS: Shotgun metagenomic sequencing identified bacterial microbiome and fungal mycobiome in tumors from individuals with eoPDAC and aoPDAC. We observed significant differences in alpha and beta diversity and relative abundances of organisms suggesting distinct microbiome signatures. Microbiome associations with survival were observed in eoPDAC indicating unique potential as prognostic biomarker.
PMID:41647993 | PMC:PMC12836659 | DOI:10.1016/j.esmogo.2025.100194
EcDNA-borne structural variants drive oncogenic fusion transcript amplification
A Human-Centered Privacy Approach (HCP) to AI
Let Experts Feel Uncertainty: A Multi-Expert Label Distribution Approach to Probabilistic Time Series Forecasting
DISCOVER: Identifying Patterns of Daily Living in Human Activities from Smart Home Data
Phenome-wide analysis of copy number variants in 470,727 UK Biobank genomes
Nature, Published online: 04 February 2026; doi:10.1038/s41586-025-10087-x
A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.