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LOSTdb: a manually curated multi-omics database for lung cancer research

BMC Bioinformatics. 2025 Dec 3;26(1):290. doi: 10.1186/s12859-025-06319-6.

ABSTRACT

Lung cancer is one of the most prevalent malignant tumors with high morbidity and mortality rates worldwide. Extensive multi-omics analyses have revealed significant intratumoral heterogeneity even within the same histopathological subtype. However, a database that systematically integrates multi-omics data for lung cancer research has long been lacking. Here, we developed LOSTdb, a molecular subtype annotation system for lung cancer that integrates multi-omics data and metadata. LOSTdb comprises 295 multi-omics datasets, including bulk RNA-seq, genomic, proteomic, methylation, and scRNA-seq data, with over 10,000 manually curated metadata entries. This resource encompasses high-quality clinical specimens, mouse models, and cell lines, totaling 34,393 samples and more than 1.2 million single cells. Each omics sample was annotated with both literature-based classical subtypes and NMF-derived meta-program (MP) subtypes. The platform supports cross-searching of omics and metadata at the gene and dataset levels, offers multiple visualization and analysis methods, and includes five tool modules, enabling functions such as integrated analysis, significance analysis between metadata as well as between genes and metadata, and target prediction for lung cancer molecular subtypes, serving as an essential tool for lung cancer precision medicine. LOSTdb is a user-friendly interactive database freely accessible at http://lostdbcancer.com:8080 .

PMID:41339793 | DOI:10.1186/s12859-025-06319-6

A Definition of AGI

arXiv:2510.18212v3 Announce Type: replace Abstract: The lack of a concrete definition for Artificial General Intelligence (AGI) obscures the gap between today's specialized AI and human-level cognition. This paper introduces a quantifiable framework to address this, defining AGI as matching the cognitive versatility and proficiency of a well-educated adult. To operationalize this, we ground our methodology in Cattell-Horn-Carroll theory, the most empirically validated model of human cognition. The framework dissects general intelligence into ten core cognitive domains-including reasoning, memory, and perception-and adapts established human psychometric batteries to evaluate AI systems. Application of this framework reveals a highly "jagged" cognitive profile in contemporary models. While proficient in knowledge-intensive domains, current AI systems have critical deficits in foundational cognitive machinery, particularly long-term memory storage. The resulting AGI scores (e.g., GPT-4 at 27%, GPT-5 at 57%) concretely quantify both rapid progress and the substantial gap remaining before AGI.

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. First, we identify a formal definition of AI deception, grounded in signaling theory from studies of animal deception. We then review existing empirical studies and associated risks, highlighting deception as a sociotechnical safety challenge. We organize the landscape of AI deception research as a deception cycle, consisting of two key components: deception emergence and deception treatment. Deception emergence reveals the mechanisms underlying AI deception: systems with sufficient capability and incentive potential inevitably engage in deceptive behaviors when triggered by external conditions. Deception treatment, in turn, focuses on detecting and addressing such behaviors. On deception emergence, we analyze incentive foundations across three hierarchical levels and identify three essential capability preconditions required for deception. We further examine contextual triggers, including supervision gaps, distributional shifts, and environmental pressures. On deception treatment, we conclude detection methods covering benchmarks and evaluation protocols in static and interactive settings. Building on the three core factors of deception emergence, we outline potential mitigation strategies and propose auditing approaches that integrate technical, community, and governance efforts to address sociotechnical challenges and future AI risks. To support ongoing work in this area, we release a living resource at www.deceptionsurvey.com.

Gut microbial metabolites in cancer immunomodulation

Mol Cancer. 2025 Dec 3. doi: 10.1186/s12943-025-02521-5. Online ahead of print.

ABSTRACT

Gut microbiota-derived metabolites are emerging as systemic "remote immunoregulators" that shape tumor immunity across tissues. Integrating evidence across short-chain fatty acids, tryptophan derivatives, secondary bile acids, polyamines and other metabolites, we advance a metabolite-immune pathway-cancer framework that links receptor-mediated signaling, epigenetic remodeling and metabolic reprogramming to context-dependent, bidirectional immune effects. Importantly, in addition to the g protein-coupled receptor / aryl hydrocarbon receptor pathway, the selected microbial small molecule metabolites are the true T-cell receptor ligands of unconventional T cells, directly shaping the tissue resident immune and tumor microenvironment, supplementing the receptor signaling and epigenetic programs in our framework. We synthesize how these metabolites recalibrate the tumor immune microenvironment-modulating antigen presentation, T-cell effector fitness and exhaustion, regulatory T-cell activity, and myeloid polarization-and why the same metabolite can either potentiate immune surveillance or entrench immunosuppression depending on ligand-receptor pairing, dose and tissue niche. We compare tumor-type specific patterns (e.g., colorectal, liver, lung, breast and prostate cancers) to highlight common circuits and organ-restricted idiosyncrasies. Methodologically, we outline how single-cell and spatial multi-omics, imaging mass spectrometry and functional biosensors now enable co-registration of metabolite exposure with immune-cell states in human tumors, providing an actionable basis for biomarker discovery. Given ongoing debate about signals attributed to intratumoral microbiota in low-biomass tumor tissues, we foreground quantifiable, spatially mappable and pharmacologically tractable metabolite-receptor pathways, using microbe-associated molecular patterns / translocation as comparators to judge when chemical signals should be prioritized as intervention targets. Finally, we evaluate precision intervention avenues-including fecal microbiota transplantation, rational bacterial consortia, engineered microbes and nanoparticle-enabled metabolite delivery-and propose stratification rules that pair metabolite/receptor signatures with fit-for-purpose delivery. Together, mapping tissue-specific metabolite-immune circuits and embedding them in robust biomarker frameworks may convert microbial metabolites from correlative markers into therapeutic targets and tools, improving the efficacy and durability of cancer immunotherapy.

PMID:41339918 | DOI:10.1186/s12943-025-02521-5

LOSTdb: a manually curated multi-omics database for lung cancer research

3 December 2025 at 19:00

BMC Bioinformatics. 2025 Dec 3;26(1):290. doi: 10.1186/s12859-025-06319-6.

ABSTRACT

Lung cancer is one of the most prevalent malignant tumors with high morbidity and mortality rates worldwide. Extensive multi-omics analyses have revealed significant intratumoral heterogeneity even within the same histopathological subtype. However, a database that systematically integrates multi-omics data for lung cancer research has long been lacking. Here, we developed LOSTdb, a molecular subtype annotation system for lung cancer that integrates multi-omics data and metadata. LOSTdb comprises 295 multi-omics datasets, including bulk RNA-seq, genomic, proteomic, methylation, and scRNA-seq data, with over 10,000 manually curated metadata entries. This resource encompasses high-quality clinical specimens, mouse models, and cell lines, totaling 34,393 samples and more than 1.2 million single cells. Each omics sample was annotated with both literature-based classical subtypes and NMF-derived meta-program (MP) subtypes. The platform supports cross-searching of omics and metadata at the gene and dataset levels, offers multiple visualization and analysis methods, and includes five tool modules, enabling functions such as integrated analysis, significance analysis between metadata as well as between genes and metadata, and target prediction for lung cancer molecular subtypes, serving as an essential tool for lung cancer precision medicine. LOSTdb is a user-friendly interactive database freely accessible at http://lostdbcancer.com:8080 .

PMID:41339793 | PMC:PMC12676782 | DOI:10.1186/s12859-025-06319-6

Scaling Multimodal Search and Recommendation with Small Language Models via Upside-Down Reinforcement Learning

arXiv:2502.09854v2 Announce Type: replace-cross Abstract: In this work, we investigate how small language models (SLMs) can be scaled to support multimodal search and recommendation use cases while remaining efficient enough for real-time, resource-constrained deployments. We present a framework that combines upside-down reinforcement learning with synthetic data distillation from a large language model (Llama-3) to train a 100M-parameter GPT-2 model for multitask prompt generation. Despite being up to 80 times smaller than state-of-the-art large language models (LLMs), our SLM achieves relevance and diversity scores within 6% of competitive baselines such as Llama-3 8B, Qwen3 8B, and Ministral 8B. These results demonstrate that SLMs can effectively handle multimodal search and recommendation tasks, while dramatically reducing inference latency and memory overhead. Our study highlights the potential of lightweight models as practical engines for scalable multimodal discovery, bridging the gap between cutting-edge research and real-world multimodal applications such as media recommendations and creative content generation.

Aetheria: A multimodal interpretable content safety framework based on multi-agent debate and collaboration

arXiv:2512.02530v1 Announce Type: new Abstract: The exponential growth of digital content presents significant challenges for content safety. Current moderation systems, often based on single models or fixed pipelines, exhibit limitations in identifying implicit risks and providing interpretable judgment processes. To address these issues, we propose Aetheria, a multimodal interpretable content safety framework based on multi-agent debate and collaboration.Employing a collaborative architecture of five core agents, Aetheria conducts in-depth analysis and adjudication of multimodal content through a dynamic, mutually persuasive debate mechanism, which is grounded by RAG-based knowledge retrieval.Comprehensive experiments on our proposed benchmark (AIR-Bench) validate that Aetheria not only generates detailed and traceable audit reports but also demonstrates significant advantages over baselines in overall content safety accuracy, especially in the identification of implicit risks. This framework establishes a transparent and interpretable paradigm, significantly advancing the field of trustworthy AI content moderation.

PaperDebugger: A Plugin-Based Multi-Agent System for In-Editor Academic Writing, Review, and Editing

arXiv:2512.02589v1 Announce Type: new Abstract: Large language models are increasingly embedded into academic writing workflows, yet existing assistants remain external to the editor, preventing deep interaction with document state, structure, and revision history. This separation makes it impossible to support agentic, context-aware operations directly within LaTeX editors such as Overleaf. We present PaperDebugger, an in-editor, multi-agent, and plugin-based academic writing assistant that brings LLM-driven reasoning directly into the writing environment. Enabling such in-editor interaction is technically non-trivial: it requires reliable bidirectional synchronization with the editor, fine-grained version control and patching, secure state management, multi-agent scheduling, and extensible communication with external tools. PaperDebugger addresses these challenges through a Chrome-approved extension, a Kubernetes-native orchestration layer, and a Model Context Protocol (MCP) toolchain that integrates literature search, reference lookup, document scoring, and revision pipelines. Our demo showcases a fully integrated workflow, including localized edits, structured reviews, parallel agent execution, and diff-based updates, encapsulated within a minimal-intrusion user interface (UI). Early aggregated analytics demonstrate active user engagement and validate the practicality of an editor-native, agentic writing assistant. More details about this demo and video could be found at https://github.com/PaperDebugger/PaperDebugger.

scCluBench: Comprehensive Benchmarking of Clustering Algorithms for Single-Cell RNA Sequencing

arXiv:2512.02471v1 Announce Type: cross Abstract: Cell clustering is crucial for uncovering cellular heterogeneity in single-cell RNA sequencing (scRNA-seq) data by identifying cell types and marker genes. Despite its importance, benchmarks for scRNA-seq clustering methods remain fragmented, often lacking standardized protocols and failing to incorporate recent advances in artificial intelligence. To fill these gaps, we present scCluBench, a comprehensive benchmark of clustering algorithms for scRNA-seq data. First, scCluBench provides 36 scRNA-seq datasets collected from diverse public sources, covering multiple tissues, which are uniformly processed and standardized to ensure consistency for systematic evaluation and downstream analyses. To evaluate performance, we collect and reproduce a range of scRNA-seq clustering methods, including traditional, deep learning-based, graph-based, and biological foundation models. We comprehensively evaluate each method both quantitatively and qualitatively, using core performance metrics as well as visualization analyses. Furthermore, we construct representative downstream biological tasks, such as marker gene identification and cell type annotation, to further assess the practical utility. scCluBench then investigates the performance differences and applicability boundaries of various clustering models across diverse analytical tasks, systematically assessing their robustness and scalability in real-world scenarios. Overall, scCluBench offers a standardized and user-friendly benchmark for scRNA-seq clustering, with curated datasets, unified evaluation protocols, and transparent analyses, facilitating informed method selection and providing valuable insights into model generalizability and application scope.

Artificial Intelligence Virtual Cells: From Measurements to Decisions across Modality, Scale, Dynamics, and Evaluation

arXiv:2510.12498v2 Announce Type: replace Abstract: Artificial Intelligence Virtual Cells (AIVCs) aim to learn executable, decision-relevant models of cell state from multimodal, multiscale measurements. Recent studies have introduced single-cell and spatial foundation models, improved cross-modality alignment, scaled perturbation atlases, and explored pathway-level readouts. Nevertheless, although held-out validation is standard practice, evaluations remain predominantly within single datasets and settings; evidence indicates that transport across laboratories and platforms is often limited, that some data splits are vulnerable to leakage and coverage bias, and that dose, time and combination effects are not yet systematically handled. Cross-scale coupling also remains constrained, as anchors linking molecular, cellular and tissue levels are sparse, and alignment to scientific or clinical readouts varies across studies. We propose a model-agnostic Cell-State Latent (CSL) perspective that organizes learning via an operator grammar: measurement, lift/project for cross-scale coupling, and intervention for dosing and scheduling. This view motivates a decision-aligned evaluation blueprint across modality, scale, context and intervention, and emphasizes function-space readouts such as pathway activity, spatial neighborhoods and clinically relevant endpoints. We recommend operator-aware data design, leakage-resistant partitions, and transparent calibration and reporting to enable reproducible, like-for-like comparisons.

AutoSurvey2: Empowering Researchers with Next Level Automated Literature Surveys

arXiv:2510.26012v3 Announce Type: replace Abstract: The rapid growth of research literature, particularly in large language models (LLMs), has made producing comprehensive and current survey papers increasingly difficult. This paper introduces autosurvey2, a multi-stage pipeline that automates survey generation through retrieval-augmented synthesis and structured evaluation. The system integrates parallel section generation, iterative refinement, and real-time retrieval of recent publications to ensure both topical completeness and factual accuracy. Quality is assessed using a multi-LLM evaluation framework that measures coverage, structure, and relevance in alignment with expert review standards. Experimental results demonstrate that autosurvey2 consistently outperforms existing retrieval-based and automated baselines, achieving higher scores in structural coherence and topical relevance while maintaining strong citation fidelity. By combining retrieval, reasoning, and automated evaluation into a unified framework, autosurvey2 provides a scalable and reproducible solution for generating long-form academic surveys and contributes a solid foundation for future research on automated scholarly writing. All code and resources are available at https://github.com/annihi1ation/auto_research.

Fast 3D Surrogate Modeling for Data Center Thermal Management

arXiv:2511.11722v2 Announce Type: replace-cross Abstract: Reducing energy consumption and carbon emissions in data centers by enabling real-time temperature prediction is critical for sustainability and operational efficiency. Achieving this requires accurate modeling of the 3D temperature field to capture airflow dynamics and thermal interactions under varying operating conditions. Traditional thermal CFD solvers, while accurate, are computationally expensive and require expert-crafted meshes and boundary conditions, making them impractical for real-time use. To address these limitations, we develop a vision-based surrogate modeling framework that operates directly on a 3D voxelized representation of the data center, incorporating server workloads, fan speeds, and HVAC temperature set points. We evaluate multiple architectures, including 3D CNN U-Net variants, a 3D Fourier Neural Operator, and 3D vision transformers, to map these thermal inputs to high-fidelity heat maps. Our results show that the surrogate models generalize across data center configurations and significantly speed up computations (20,000x), from hundreds of milliseconds to hours. This fast and accurate estimation of hot spots and temperature distribution enables real-time cooling control and workload redistribution, leading to substantial energy savings (7\%) and reduced carbon footprint.

Multi-omic profiling provides insights into the heterogeneity, microenvironmental features, and biomarker landscape of small-cell lung cancer

Mol Cancer. 2025 Dec 2. doi: 10.1186/s12943-025-02514-4. Online ahead of print.

ABSTRACT

BACKGROUND: Greater understanding of differential therapeutic sensitivity, specifically to immunotherapy, in small-cell lung cancer (SCLC) is required.

METHODS: We explored SCLC heterogeneity through integrated molecular characterization of tumor tissue samples from 159 treatment-naive patients, utilizing genetic, epigenetic, transcriptional, and proteomic profiling, immunohistochemistry staining for multiple biologically relevant markers including transcriptional subtype-defining proteins, and spatial immune profiling using multiplex immunofluorescence.

RESULTS: Multi-omics analysis confirmed high heterogeneity across/within neuroendocrine and non-neuroendocrine subtypes. Methylomics analysis identified four methylome clusters that may enhance subtype prediction, prognosis, and longitudinal monitoring of subtype evolution. Immunohistochemistry analysis showed high MHC-I expression in non-neuroendocrine subtypes, which have greatest potential benefit from adding immunotherapy to chemotherapy; high DLL3 expression associated with neuroendocrine subtypes and an immune-cold tumor microenvironment. Multiplex immunofluorescence demonstrated associations of MHC-I with spatial arrangement and phenotypic features of immune cells in the tumor microenvironment of high-MHC-I-expressing SCLC, providing mechanistic rationale for MHC-I as a potential biomarker of immunotherapy response.

CONCLUSIONS: This multimodal profiling analysis provides further insights into the biologic complexity of SCLC and highlights potential therapeutic vulnerabilities of distinct disease subtypes.

PMID:41331472 | DOI:10.1186/s12943-025-02514-4

Integrative Analysis of Multi-Omics Data for Biomarker Discovery

Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-7. doi: 10.1109/EMBC58623.2025.11254134.

ABSTRACT

The complexity of biological systems and the limitations of analyzing individual omics studies for biomarker discovery have raised the need for a holistic approach by multi-omics integration. By integrating data from multiple layers, researchers can gain insights into the entire system rather than just individual components. Also, integrative analysis can help identify molecular signatures that are more accurate in predicting disease onset, progression, and response to treatment, leading to better-targeted therapies and personalized medicine. In this paper, we explored statistical and deep learning methods for integrative analysis of metabolomics, lipidomics, peptidomics, proteomics, and glycoproteomics data acquired by LC-MS/MS analysis of serum samples from 20 hepatocellular carcinoma (HCC) cases and 20 patients with liver cirrhosis (CIRR). The goal is to identify a panel of multi-omics features that distinguish HCC cases from cirrhotic controls. A pathway analysis using these features identified biological pathways such as LXR/RXR Activation and Acute Response signaling as significantly enriched in our multi-omics datasets.

PMID:41336317 | PMC:PMC12694951 | DOI:10.1109/EMBC58623.2025.11254134

Whole-genome landscapes of 1,364 breast cancers

Nature, Published online: 03 December 2025; doi:10.1038/s41586-025-09812-3

Whole-genome and transcriptome analysis of 1,364 cases of breast cancer from South Korea broadens our understanding of breast cancer biology and reveals genomic features that connect tumour biology with treatment responses and clinical outcomes.
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