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DAQ: Delta-Aware Quantization for Post-Training LLM Weight Compression

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xiaoming Yu · Shize Tang · Guanghua Yu · Linchuan Xie · Song Liu · Jianchen Zhu · Feng Li
arXiv:2603.22324v1 Announce Type: cross Abstract: We introduce Delta-Aware Quantization (DAQ), a data-free post-training quantization framework that preserves the knowledge acquired during post-training. Standard quantization objectives minimize reconstruction error but are agnostic to the base model, allowing quantization noise to disproportionately corrupt the small-magnitude parameter deltas ($\Delta W$) that encode post-training behavior -- an effect we analyze through the lens of quantization as implicit regularization. DAQ replaces reconstruction-based objectives with two delta-aware metrics -- Sign Preservation Rate and Cosine Similarity -- that directly optimize for directional fidelity of $\Delta W$, requiring only the base and post-trained weight matrices. In a pilot FP8 study, DAQ recovers style-specific capabilities lost under standard quantization while maintaining general performance.
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Three Creates All: You Only Sample 3 Steps

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yuren Cai · Guangyi Wang · Zongqing Li · Li Li · Zhihui Liu · Songzhi Su
arXiv:2603.22375v1 Announce Type: cross Abstract: Diffusion models deliver high-fidelity generation but remain slow at inference time due to many sequential network evaluations. We find that standard timestep conditioning becomes a key bottleneck for few-step sampling. Motivated by layer-dependent denoising dynamics, we propose Multi-layer Time Embedding Optimization (MTEO), which freeze the pretrained diffusion backbone and distill a small set of step-wise, layer-wise time embeddings from reference trajectories. MTEO is plug-and-play with existing ODE solvers, adds no inference-time overhead, and trains only a tiny fraction of parameters. Extensive experiments across diverse datasets and backbones show state-of-the-art performance in the few-step sampling and substantially narrow the gap between distillation-based and lightweight methods. Code will be available.
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CaP-X: A Framework for Benchmarking and Improving Coding Agents for Robot Manipulation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Max Fu, Justin Yu, Karim El-Refai, Ethan Kou, Haoru Xue, Huang Huang, Wenli Xiao, Guanzhi Wang, Fei-Fei Li, Guanya Shi, Jiajun Wu, Shankar Sastry, Yuke Zhu, Ken Goldberg, Linxi "Jim" Fan
arXiv:2603.22435v1 Announce Type: cross Abstract: "Code-as-Policy" considers how executable code can complement data-intensive Vision-Language-Action (VLA) methods, yet their effectiveness as autonomous controllers for embodied manipulation remains underexplored. We present CaP-X, an open-access framework for systematically studying Code-as-Policy agents in robot manipulation. At its core is CaP-Gym, an interactive environment in which agents control robots by synthesizing and executing programs that compose perception and control primitives. Building on this foundation, CaP-Bench evaluates frontier language and vision-language models across varying levels of abstraction, interaction, and perceptual grounding. Across 12 models, CaP-Bench reveals a consistent trend: performance improves with human-crafted abstractions but degrades as these priors are removed, exposing a dependence on designer scaffolding. At the same time, we observe that this gap can be mitigated through scaling agentic test-time computation--through multi-turn interaction, structured execution feedback, visual differencing, automatic skill synthesis, and ensembled reasoning--substantially improves robustness even when agents operate over low-level primitives. These findings allow us to derive CaP-Agent0, a training-free framework that recovers human-level reliability on several manipulation tasks in simulation and on real embodiments. We further introduce CaP-RL, showing reinforcement learning with verifiable rewards improves success rates and transfers from sim2real with minimal gap. Together, CaP-X provides a principled, open-access platform for advancing embodied coding agents.
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Operational machine learning for remote spectroscopic detection of CH$_{4}$ point sources

✇cs.AI, q-bio.NC updates on arXiv.org
By: V\'it R\r{u}\v{z}i\v{c}ka · Gonzalo Mateo-Garc\'ia · Itziar Irakulis-Loitxate · Juan Emmanuel Johnson · Manuel Montesino San Mart\'in · Anna Allen · Alma Raunak · Carol Castaneda · Luis Guanter · David R. Thompson
arXiv:2511.07719v2 Announce Type: replace Abstract: Mitigating anthropogenic methane sources is one of the most cost-effective levers to slow down global warming. While satellite-based imaging spectrometers, such as EMIT, PRISMA, and EnMAP, can detect these point sources, current methane retrieval methods based on matched filters produce a high number of false detections requiring manual verification. To address this challenge, we deployed a ML system for detecting methane emissions within the Methane Alert and Response System (MARS) of UNEP's IMEO. This represents the first operational deployment of automated methane point-source detection using spaceborne imaging spectrometers, providing regular global coverage and scalability to future constellations with even higher data volumes. This task required several technical advances. First, we created one of the largest and most diverse and global ML ready datasets to date of annotated methane plumes from three imaging spectrometer missions, and quantitatively compared different deep learning model configurations. Second, we extended prior evaluation methodologies from small, tiled datasets to full granules that are more representative of operational use. This revealed that deep learning models still produce a large number of false detections, a problem we addressed with model ensembling, which reduced false detections by over 74%. During 11 months of operational deployment, our system processed more than 25,000 hyperspectral products faciliting the verification of 2,851 distinct methane leaks, which resulted in 834 stakeholder notifications. We further demonstrate the model's utility in verifying mitigation success through case studies in Libya, Argentina, Oman, and Azerbaijan. Our work represents a critical step towards a global AI-assisted methane leak detection system, which is required to process the dramatically higher data volumes expected from current and future imaging spectrometers.
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Rethinking the Role of Entropy in Optimizing Tool-Use Behaviors for Large Language Model Agents

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zeping Li · Hongru Wang · Yiwen Zhao · Guanhua Chen · Yixia Li · Keyang Chen · Yixin Cao · Guangnan Ye · Hongfeng Chai · Zhenfei Yin
arXiv:2602.02050v3 Announce Type: replace Abstract: Tool-using agents based on Large Language Models (LLMs) excel in tasks such as mathematical reasoning and multi-hop question answering. However, in long trajectories, agents often trigger excessive and low-quality tool calls, increasing latency and degrading inference performance, making managing tool-use behavior challenging. In this work, we conduct entropy-based pilot experiments and observe a strong positive correlation between entropy reduction and high-quality tool calls. Building on this finding, we propose using entropy reduction as a supervisory signal and design two reward strategies to address the differing needs of optimizing tool-use behavior. Sparse outcome rewards provide coarse, trajectory-level guidance to improve efficiency, while dense process rewards offer fine-grained supervision to enhance performance. Experiments across diverse domains show that both reward designs improve tool-use behavior: the former reduces tool calls by 72.07% compared to the average of baselines, while the latter improves performance by 22.27%. These results position entropy reduction as a key mechanism for enhancing tool-use behavior, enabling agents to be more adaptive in real-world applications.
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Generalizable Heuristic Generation Through LLMs with Meta-Optimization

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yiding Shi · Jianan Zhou · Wen Song · Jieyi Bi · Yaoxin Wu · Zhiguang Cao · Jie Zhang
arXiv:2505.20881v2 Announce Type: replace-cross Abstract: Heuristic design with large language models (LLMs) has emerged as a promising approach for tackling combinatorial optimization problems (COPs). However, existing approaches often rely on manually predefined evolutionary computation (EC) heuristic-optimizers and single-task training schemes, which may constrain the exploration of diverse heuristic algorithms and hinder the generalization of the resulting heuristics. To address these issues, we propose Meta-Optimization of Heuristics (MoH), a novel framework that operates at the optimizer level, discovering effective heuristic-optimizers through the principle of meta-learning. Specifically, MoH leverages LLMs to iteratively refine a meta-optimizer that autonomously constructs diverse heuristic-optimizers through (self-)invocation, thereby eliminating the reliance on a predefined EC heuristic-optimizer. These constructed heuristic-optimizers subsequently evolve heuristics for downstream tasks, enabling broader heuristic exploration. Moreover, MoH employs a multi-task training scheme to promote its generalization capability. Experiments on classic COPs demonstrate that MoH constructs an effective and interpretable meta-optimizer, achieving state-of-the-art performance across various downstream tasks, particularly in cross-size settings. Our code is available at: https://github.com/yiding-s/MoH.
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From Noisy Labels to Intrinsic Structure: A Geometric-Structural Dual-Guided Framework for Noise-Robust Medical Image Segmentation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Tao Wang · Zhenxuan Zhang · Yuanbo Zhou · Xinlin Zhang · Yuanbin Chen · Tao Tan · Guang Yang · Tong Tong
arXiv:2509.02419v2 Announce Type: replace-cross Abstract: The effectiveness of convolutional neural networks in medical image segmentation relies on large-scale, high-quality annotations, which are costly and time-consuming to obtain. Even expert-labeled datasets inevitably contain noise arising from subjectivity and coarse delineations, which disrupt feature learning and adversely impact model performance. To address these challenges, this study propose a Geometric-Structural Dual-Guided Network (GSD-Net), which integrates geometric and structural cues to improve robustness against noisy annotations. It incorporates a Geometric Distance-Aware module that dynamically adjusts pixel-level weights using geometric features, thereby strengthening supervision in reliable regions while suppressing noise. A Structure-Guided Label Refinement module further refines labels with structural priors, and a Knowledge Transfer module enriches supervision and improves sensitivity to local details. To comprehensively assess its effectiveness, we evaluated GSD-Net on six publicly available datasets: four containing three types of simulated label noise, and two with multi-expert annotations that reflect real-world subjectivity and labeling inconsistencies. Experimental results demonstrate that GSD-Net achieves state-of-the-art performance under noisy annotations, achieving improvements of 1.58% on Kvasir, 22.76% on Shenzhen, 8.87% on BU-SUC, and 1.77% on BraTS2020 under SR simulated noise. The codes of this study are available at https://github.com/ortonwang/GSD-Net.
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Information Gain-based Policy Optimization: A Simple and Effective Approach for Multi-Turn Search Agents

✇cs.AI, q-bio.NC updates on arXiv.org
By: Guoqing Wang · Sunhao Dai · Guangze Ye · Zeyu Gan · Wei Yao · Yong Deng · Xiaofeng Wu · Zhenzhe Ying
arXiv:2510.14967v2 Announce Type: replace-cross Abstract: Large language model (LLM)-based agents are increasingly trained with reinforcement learning (RL) to enhance their ability to interact with external environments through tool use, particularly in search-based settings that require multi-turn reasoning and knowledge acquisition. However, existing approaches typically rely on outcome-based rewards that are only provided exclusively upon generating the final answer. This reward sparsity becomes particularly problematic in multi-turn settings, where long trajectories exacerbate three critical issues: (i) advantage collapse, where all rollouts receive identical rewards and provide no useful learning signals; (ii) lack of fine-grained credit assignment, where the correctness of intermediate turns is obscured, especially in long-horizon tasks; and (iii) poor sample efficiency, where each rollout yields only a single outcome signal, leading to low data utilization. In this paper, we propose Information Gain-based Policy Optimization (IGPO), a simple yet effective RL framework that provides dense and intrinsic supervision for multi-turn agent training. IGPO models each interaction turn as an incremental process of acquiring information about the ground truth, and defines turn-level rewards as the marginal increase in the policy's probability of producing the correct answer. Unlike prior process-level reward approaches that depend on external reward models or costly Monte Carlo estimation, IGPO derives intrinsic rewards directly from the model's own belief updates. These intrinsic turn-level rewards are combined with outcome-level supervision to form dense reward signals. Extensive experiments on both in-domain and out-of-domain benchmarks demonstrate that IGPO consistently outperforms strong baselines in multi-turn scenarios, achieving higher accuracy and improved data efficiency. Our code is available at https://github.com/GuoqingWang1/IGPO.
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MOON2.0: Dynamic Modality-balanced Multimodal Representation Learning for E-commerce Product Understanding

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zhanheng Nie · Chenghan Fu · Daoze Zhang · Junxian Wu · Wanxian Guan · Pengjie Wang · Jian Xu · Bo Zheng
arXiv:2511.12449v2 Announce Type: replace-cross Abstract: Recent Multimodal Large Language Models (MLLMs) have significantly advanced e-commerce product understanding. However, they still face three challenges: (i) the modality imbalance induced by modality mixed training; (ii) underutilization of the intrinsic alignment relationships among visual and textual information within a product; and (iii) limited handling of noise in e-commerce multimodal data. To address these, we propose MOON2.0, a dynamic modality-balanced MultimOdal representation learning framework for e-commerce prOduct uNderstanding. It comprises: (1) a Modality-driven Mixture-of-Experts (MoE) that adaptively processes input samples by their modality composition, enabling Multimodal Joint Learning to mitigate the modality imbalance; (2) a Dual-level Alignment method to better leverage semantic alignment properties inside individual products; and (3) an MLLM-based Image-text Co-augmentation strategy that integrates textual enrichment with visual expansion, coupled with Dynamic Sample Filtering to improve training data quality. We further release MBE2.0, a co-augmented Multimodal representation Benchmark for E-commerce representation learning and evaluation at https://huggingface.co/datasets/ZHNie/MBE2.0. Experiments show that MOON2.0 delivers state-of-the-art zero-shot performance on MBE2.0 and multiple public datasets. Furthermore, attention-based heatmap visualization provides qualitative evidence of improved multimodal alignment of MOON2.0.
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Schr\"odinger's Navigator: Imagining an Ensemble of Futures for Zero-Shot Object Navigation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yu He · Da Huang · Zhenyang Liu · Zixiao Gu · Qiang Sun · Guangnan Ye · Yanwei Fu · Yu-Gang Jiang
arXiv:2512.21201v2 Announce Type: replace-cross Abstract: Zero-shot object navigation (ZSON) requires robots to locate target objects in unseen environments without task-specific fine-tuning or pre-built maps, a capability crucial for service and household robotics. Existing methods perform well in simulation but struggle in realistic, cluttered environments where heavy occlusions and latent hazards make large portions of the scene unobserved. These approaches typically act on a single inferred scene, making them prone to overcommitment and unsafe behavior under uncertainty. To address these challenges, we propose Schr\"odinger's Navigator, a belief-aware framework that explicitly reasons over multiple trajectory-conditioned imagined 3D futures at inference time. A trajectory-conditioned 3D world model generates hypothetical observations along candidate paths, maintaining a superposition of plausible scene realizations. An adaptive, occluder-aware trajectory sampling strategy focuses imagination on uncertain regions, while a Future-Aware Value Map (FAVM) aggregates imagined futures to guide robust, proactive action selection. Evaluations in simulation and on a physical Go2 quadruped robot demonstrate that Schr\"odinger's Navigator outperforms strong ZSON baselines, achieving more robust self-localization, object localization, and safe navigation under severe occlusions and latent hazards. These results highlight the effectiveness of reasoning over imagined 3D futures as a scalable and generalizable strategy for zero-shot navigation in uncertain real-world environments.
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VLM-CAD: VLM-Optimized Collaborative Agent Design Workflow for Analog Circuit Sizing

✇cs.AI, q-bio.NC updates on arXiv.org
By: Guanyuan Pan · Shuai Wang · Yugui Lin · Tiansheng Zhou · Pietro Li\`o · Zhenxin Zhao · Yaqi Wang
arXiv:2601.07315v4 Announce Type: replace-cross Abstract: Vision Language Models (VLMs) have demonstrated remarkable potential in multimodal reasoning, yet they inherently suffer from spatial blindness and logical hallucinations when interpreting densely structured engineering content, such as analog circuit schematics. To address these challenges, we propose a Vision Language Model-Optimized Collaborative Agent Design Workflow for Analog Circuit Sizing (VLM-CAD) designed for robust, step-by-step reasoning over multimodal evidence. VLM-CAD bridges the modality gap by integrating a neuro-symbolic structural parsing module, Image2Net, which transforms raw pixels into explicit topological graphs and structured JSON representations to anchor VLM interpretation in deterministic facts. To ensure the reliability required for engineering decisions, we further propose ExTuRBO, an Explainable Trust Region Bayesian Optimization method. ExTuRBO serves as an explainable grounding engine, employing agent-generated semantic seeds to warm-start local searches and utilizing Automatic Relevance Determination to provide quantified evidence for the VLM's decisions. Experimental results on two complex circuit benchmarks demonstrate that VLM-CAD significantly enhances spatial reasoning accuracy and maintains physics-based explainability. VLM-CAD consistently satisfies complex specification requirements while achieving low power consumption, with a total runtime under 66 minutes, marking a significant step toward robust, explainable multimodal reasoning in specialized technical domains.
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FlyPrompt: Brain-Inspired Random-Expanded Routing with Temporal-Ensemble Experts for General Continual Learning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Hongwei Yan · Guanglong Sun · Kanglei Zhou · Qian Li · Liyuan Wang · Yi Zhong
arXiv:2602.01976v3 Announce Type: replace-cross Abstract: General continual learning (GCL) challenges intelligent systems to learn from single-pass, non-stationary data streams without clear task boundaries. While recent advances in continual parameter-efficient tuning (PET) of pretrained models show promise, they typically rely on multiple training epochs and explicit task cues, limiting their effectiveness in GCL scenarios. Moreover, existing methods often lack targeted design and fail to address two fundamental challenges in continual PET: how to allocate expert parameters to evolving data distributions, and how to improve their representational capacity under limited supervision. Inspired by the fruit fly's hierarchical memory system characterized by sparse expansion and modular ensembles, we propose FlyPrompt, a brain-inspired framework that decomposes GCL into two subproblems: expert routing and expert competence improvement. FlyPrompt introduces a randomly expanded analytic router for instance-level expert activation and a temporal ensemble of output heads to dynamically adapt decision boundaries over time. Extensive theoretical and empirical evaluations demonstrate FlyPrompt's superior performance, achieving up to 11.23%, 12.43%, and 7.62% gains over state-of-the-art baselines on CIFAR-100, ImageNet-R, and CUB-200, respectively. Our source code is available at https://github.com/AnAppleCore/FlyGCL.
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Behavioral Consistency Validation for LLM Agents: An Analysis of Trading-Style Switching through Stock-Market Simulation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zeping Li · Guancheng Wan · Keyang Chen · Yu Chen · Yiwen Zhao · Philip Torr · Guangnan Ye · Zhenfei Yin · Hongfeng Chai
arXiv:2602.07023v2 Announce Type: replace-cross Abstract: Recent works have increasingly applied Large Language Models (LLMs) as agents in financial stock market simulations to test if micro-level behaviors aggregate into macro-level phenomena. However, a crucial question arises: Do LLM agents' behaviors align with real market participants? This alignment is key to the validity of simulation results. To explore this, we select a financial stock market scenario to test behavioral consistency. Investors are typically classified as fundamental or technical traders, but most simulations fix strategies at initialization, failing to reflect real-world trading dynamics. In this work, we assess whether agents' strategy switching aligns with financial theory, providing a framework for this evaluation. We operationalize four behavioral-finance drivers-loss aversion, herding, wealth differentiation, and price misalignment-as personality traits set via prompting and stored long-term. In year-long simulations, agents process daily price-volume data, trade under a designated style, and reassess their strategy every 10 trading days. We introduce four alignment metrics and use Mann-Whitney U tests to compare agents' style-switching behavior with financial theory. Our results show that recent LLMs' switching behavior is only partially consistent with behavioral-finance theories, highlighting the need for further refinement in aligning agent behavior with financial theory.
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Children's Intelligence Tests Pose Challenges for MLLMs? KidGym: A 2D Grid-Based Reasoning Benchmark for MLLMs

✇cs.AI, q-bio.NC updates on arXiv.org
By: Hengwei Ye · Yuanting Guan · Yuxuan Ge · Tianying Zhu · Zhenhan Guan · Yijia Zhong · Yijing Zhang · Han Zhang · Yingna Wu · Zheng Tian
arXiv:2603.20209v2 Announce Type: replace-cross Abstract: Multimodal Large Language Models (MLLMs) combine the linguistic strengths of LLMs with the ability to process multimodal data, enbaling them to address a broader range of visual tasks. Because MLLMs aim at more general, human-like competence than language-only models, we take inspiration from the Wechsler Intelligence Scales - an established battery for evaluating children by decomposing intelligence into interpretable, testable abilities. We introduce KidGym, a comprehensive 2D grid-based benchmark for assessing five essential capabilities of MLLMs: Execution, Perception Reasoning, Learning, Memory and Planning. The benchmark comprises 12 unique tasks, each targeting at least one core capability, specifically designed to guage MLLMs' adaptability and developmental potential, mirroring the stages of children's cognitive growth. Additionally, our tasks encompass diverse scenarios and objects with randomly generated layouts, ensuring a more accurate and robust evluation of MLLM capabilities. KidGym is designed to be fully user-customizable and extensible, allowing researchers to create new evaluation scenarios and adjust difficuly levels to accommodate the rapidly growing MLLM community. Through the evaluation of state-of-the-art MLLMs using KidGym, we identified significant insights into model capabilities and revealed several limitations of current models. We release our benchmark at: https://bobo-ye.github.io/KidGym/.
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Boosting foundation models for rare eye disease diagnosis via a multimodal text-to-image generative framework

✇npj Digital Medicine
By: Ruoyu Chen · Weiyi Zhang · Bowen Liu · Xinyuan Wu · Xiaolan Chen · Pusheng Xu · Shunming Liu · Mingguang He · Danli Shi

npj Digital Medicine, Published online: 24 March 2026; doi:10.1038/s41746-026-02560-2

Boosting foundation models for rare eye disease diagnosis via a multimodal text-to-image generative framework
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TRIM21-mediated degradation of HILPDA overcomes anti-PD-1 immunotherapy resistance in breast cancer by limiting PD-L1 palmitoylation

✇Oncogene - Issue - nature.com science feeds
By: Xi Wang · Guangyan Li · Jiaming Wu · Baiyang Fu · Haoyang Zhang · Yichi Chen · Jianjiao Wang · Jianguo Zhang · Xi Chen

Oncogene, Published online: 24 March 2026; doi:10.1038/s41388-026-03728-6

TRIM21-mediated degradation of HILPDA overcomes anti-PD-1 immunotherapy resistance in breast cancer by limiting PD-L1 palmitoylation
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Unannotated noncoding transcripts as a source of intratumor heterogeneity in malignant cell states

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Xiaolan Zhou · Limin Lin · Yu Chen · Guangrui Yang · Ting Ni · Zhaozhao Zhao

Sci China Life Sci. 2026 Mar 16. doi: 10.1007/s11427-025-3273-6. Online ahead of print.

ABSTRACT

Phenotypic diversity of malignant cells within a tumor underlies intratumor heterogeneity (ITH), a key determinant of cancer metastasis and treatment failure. However, the molecular mechanisms driving this heterogeneity are poorly understood. Here, we curated and analyzed a cohort of 3' tag-based single-cell RNA-seq covering 12 common cancer types. We identified thousands of poly(A) site (PAS) peaks representing the 3' ends of previously unannotated transcripts, whose expression is widely associated with diverse malignant cellular states. By integrating multi-omics data, we characterized the expression patterns and epigenetic landscape of these unannotated PAS peak-associated transcripts (UPTs). The expression heterogeneity of UPTs was supported by multi-region sampling bulk RNA-seq data and recapitulated within cancer cell lines. As proof of principle validation, functional experiments confirmed that two noncoding UPTs promoted the proliferation and migration of lung cancer cells. Our results suggest that epigenetic activation of unannotated noncoding transcripts might represent a previously unrecognized mechanism contributing to transcriptomic ITH.

PMID:41870780 | DOI:10.1007/s11427-025-3273-6

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Spatial Omics in Gastrointestinal Oncology: Recent Advances, Therapeutic Insights, and Clinical Translation

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Lin Zhong · Qian Li · Ting Xiong · Shengzheng Lin · Kaining Wang · Guanying Li · Ye Yan · Jianhao Liu · Chuansong Xue

J Cancer. 2026 Jan 30;17(3):515-523. doi: 10.7150/jca.127381. eCollection 2026.

ABSTRACT

Gastrointestinal (GI) cancers remain a leading cause of cancer-related morbidity and mortality worldwide, largely due to their molecular heterogeneity, complex tumor microenvironment (TME), and variable treatment responses. In recent years, the emergence of spatially resolved omics technologies-encompassing spatial transcriptomics, proteomics, metabolomics, and epigenomics-has revolutionized the ability to interrogate tumor architecture with unprecedented resolution. These methods enable precise mapping of cellular and molecular interactions within intact tissue contexts, thereby uncovering spatially defined niches that influence tumor progression, immune evasion, and therapeutic resistance. In GI malignancies such as colorectal, gastric, and esophageal cancers, spatial omics have provided critical insights into cancer-stromal-immune crosstalk, identified predictive biomarkers for immunotherapy and targeted agents, and guided the development of novel therapeutic strategies. This review synthesizes the latest advances in spatial omics applied to GI oncology over the past five years, with an emphasis on their integration into early diagnosis, treatment stratification, and real-time monitoring of therapeutic efficacy. We also discuss current challenges, including standardization, data integration, and clinical validation, as well as future directions for incorporating spatial profiling into routine oncology practice. By bridging the gap between bench discoveries and bedside applications, spatial omics hold transformative potential for achieving truly personalized treatment in gastrointestinal cancers.

PMID:41869445 | PMC:PMC13003551 | DOI:10.7150/jca.127381

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Unannotated noncoding transcripts as a source of intratumor heterogeneity in malignant cell states

✇Omics In Lung
By: Xiaolan Zhou · Limin Lin · Yu Chen · Guangrui Yang · Ting Ni · Zhaozhao Zhao

Sci China Life Sci. 2026 Mar 16. doi: 10.1007/s11427-025-3273-6. Online ahead of print.

ABSTRACT

Phenotypic diversity of malignant cells within a tumor underlies intratumor heterogeneity (ITH), a key determinant of cancer metastasis and treatment failure. However, the molecular mechanisms driving this heterogeneity are poorly understood. Here, we curated and analyzed a cohort of 3' tag-based single-cell RNA-seq covering 12 common cancer types. We identified thousands of poly(A) site (PAS) peaks representing the 3' ends of previously unannotated transcripts, whose expression is widely associated with diverse malignant cellular states. By integrating multi-omics data, we characterized the expression patterns and epigenetic landscape of these unannotated PAS peak-associated transcripts (UPTs). The expression heterogeneity of UPTs was supported by multi-region sampling bulk RNA-seq data and recapitulated within cancer cell lines. As proof of principle validation, functional experiments confirmed that two noncoding UPTs promoted the proliferation and migration of lung cancer cells. Our results suggest that epigenetic activation of unannotated noncoding transcripts might represent a previously unrecognized mechanism contributing to transcriptomic ITH.

PMID:41870780 | DOI:10.1007/s11427-025-3273-6

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