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01.
arXiv (CS.AI) 2026-06-15

Hybrid Open-Ended Tri-Evolution Makes Better Deep Researcher

arXiv:2606.13710v1 Announce Type: new Abstract: Deep research and agent evolution serve as de-facto tasks for AI agents in real-world applications toward artificial general intelligence. The former enables autonomous retrieval and integration of information in open-ended environments to tackle open-ended research tasks, yet it is constrained by the static parametric deep research capabilities of agent systems. The latter allows agents to autonomously interact with the environment to gain experiences that evolve model capabilities. However, its effectiveness has been widely validated only on verifiable tasks with standard answers, leaving a gap with open-ended research tasks. To bridge these two critical tasks, we propose the Hybrid Open-Ended Tri-Evolution (HOTE) framework, which leverages hybrid-mode reinforcement learning to facilitate the collaborative evolution of a proposer, solver and judge based on web-scale knowledge, moving toward autonomous evolving agents in open-ended tasks and environments. Extensive experiments on three long-form deep research benchmarks demonstrate that the 8B model trained via HOTE surpasses the strongest static open 8-32B models as well as those trained by state-of-the-art deep research training methods with less time overhead, and further verify that the evolution of all three modules in HOTE is indispensable.

02.
arXiv (CS.LG) 2026-06-19

MolGraphBench: A Benchmark of GNN Architectures for Molecular Regression Tasks

arXiv:2602.20573v3 Announce Type: replace Abstract: Molecules are often represented as SMILES strings, which can be readily converted to hand-crafted descriptors or fingerprints (FP) for molecular property prediction. Research has demonstrated that SMILES can be converted to molecular graphs $G = (V, E)$, with atoms as nodes $(V)$ and bonds as edges $(E)$. These molecular graphs can subsequently be used to train graph neural networks (GNN) models. Despite the recent surge in application of GNN (existing and novel architectures) for molecular property prediction, a rigorous benchmark is still lacking. We propose MolGraphBench, a comprehensive benchmark of four commonly used GNN models for molecular property prediction. Benchmarking results demonstrate graph convolutional network (GCN) and graph isomorphism networks (GIN) as the optimal GNN architectures for molecular graph regression tasks, based on absolute performance, training efficiency, transfer learning and prediction quality. The study also indicates the non-complementary nature of molecular fingerprints in the fusion (GNN-FP) framework. Furthermore, our GNN models achieved performance superior or comparable performance to current state-of-the-art GNN baselines across three datasets (GCN with RMSE of $0.518$ on B3DB, GIN-FP with RMSE of $1.022$ on FreeSolv and GIN with MAE of $63.783$ on RT datasets). Findings from this study indicate that type of GNN-layer, should be treated as a tunable hyperparameter rather than a fixed design choice to achieve superior performance.

03.
arXiv (CS.LG) 2026-06-16

EnvShip-Bench: An Environment-Enhanced Benchmark for Short-Term Vessel Trajectory Prediction

arXiv:2606.15240v1 Announce Type: new Abstract: Vessel trajectory prediction is important for intelligent shipping, maritime surveillance, and navigation safety. However, existing public maritime AIS resources are often limited by inconsistent forecasting protocols, uneven data quality, and the lack of benchmark-ready contextual annotations, which hinder fair comparison and context-aware modeling. To address this gap, we present EnvShip-Bench, a unified benchmark for short-term vessel trajectory prediction built from large-scale raw AIS data from the Danish Maritime Authority (DMA) and NOAA through a common processing pipeline. EnvShip-Bench adopts a standardized forecasting protocol with 10 minutes of observation, 10 minutes of prediction, and 20-second sampling in vessel-centric local metric coordinates. Beyond the large-scale core benchmark, it provides a quality-first compact subset for efficient and reproducible experimentation, together with synchronized environmental and nearby-vessel context extensions. As a result, EnvShip-Bench supports trajectory-only, environment-aware, and interaction-aware forecasting under a unified evaluation framework. Extensive benchmark statistics and analysis demonstrate that EnvShip-Bench offers a standardized, extensible, and context-aware foundation for maritime trajectory forecasting research.

05.
arXiv (CS.CV) 2026-06-15

Digital Twin Driven Textile Classification and Foreign Object Recognition in Automated Sorting Systems

The increasing demand for sustainable textile recycling requires robust automation solutions capable of handling deformable garments and detecting foreign objects in cluttered environments. This work presents a digital twin driven robotic sorting system that integrates grasp prediction, multi modal perception, and semantic reasoning for real world textile classification. A dual arm robotic cell equipped with RGBD sensing, capacitive tactile feedback, and collision-aware motion planning autonomously separates garments from an unsorted basket, transfers them to an inspection zone, and classifies them using state of the art Visual Language Models (VLMs). We benchmark nine VLM s from five model families on a dataset of 223 inspection scenarios comprising shirts, socks, trousers, underwear, foreign objects (including garments outside of the aforementioned classes), and empty scenes. The evaluation assesses per class accuracy, hallucination behavior, and computational performance under practical hardware constraints. Results show that the Qwen model family achieves the highest overall accuracy (up to 87.9 %), with strong foreign object detection performance, while lighter models such as Gemma3 offer competitive speed accuracy trade offs for edge deployment. A digital twin combined with MoveIt enables collision aware path planning and integrates segmented 3D point clouds of inspected garments into the virtual environment for improved manipulation reliability. The presented system demonstrates the feasibility of combining semantic VLM reasoning with conventional grasp detection and digital twin technology for scalable, autonomous textile sorting in realistic industrial settings.

06.
arXiv (CS.CV) 2026-06-11

AnchorEdit: Maintaining Temporal Consistency in Multi-turn Image Editing via Causal Memory

Multi-turn image editing is essential for iterative design, yet current models often struggle with identity drift and error accumulation over successive steps. While existing research leverages video priors for consistency, their reliance on bidirectional attention is fundamentally misaligned with the causal, sequential nature of interactive editing. In this paper, we propose AnchorEdit, the first autoregressive (AR) diffusion-based framework designed specifically for high-resolution, long-term multi-turn editing. AnchorEdit bridges the gap between video priors and causal inference through a three-stage training curriculum: identity-preserving sing-turn pretraining, causal AR forcing fine-tuning with a novel self-rollout strategy to mitigate exposure bias, and consistency distillation for efficient 4-step generation. During inference, we introduce a memory mechanism to anchor the initial subject identity and ensure stable extrapolation across extended editing trajectories. To evaluate performance, we provide a new high-resolution multi-turn editing benchmark designed to stress-test long-horizon stability. Extensive experiments demonstrate that AnchorEdit achieves state-of-the-art results, maintaining exceptional subject fidelity and instruction following even over 10+ interaction rounds.

07.
arXiv (CS.CL) 2026-06-12

HyperTool: Beyond Step-Wise Tool Calls for Tool-Augmented Agents

Tool-augmented LLM agents commonly rely on step-wise atomic tool calls, where each invocation, observation, and value transfer is exposed in the main reasoning trace. This creates an execution-granularity mismatch: locally deterministic tool workflows are unfolded into repeated model-visible decisions, consuming context and forcing the model to manage low-level dataflow in the trace. We introduce HyperTool, a unified executable MCP-style tool interface that changes the model-visible unit of tool execution. A model invokes HyperTool with a code block that can call existing tools through their original schemas, manipulate returned values, and pass intermediate results locally, folding deterministic tool subroutines into a single outer call. To train models to use this interface, we synthesize HyperTool-format trajectories from cross-tool compositional tasks and verify them in real MCP environments. On MCP-Universe, HyperTool improves average accuracy from 15.69\% to 35.29\% on Qwen3-32B and from 9.93\% to 33.33\% on Qwen3-8B, and surpass GPT-OSS and Kimi-k2.5 on average accuracy, showing that our HyperTool can substantially improve multi-step tool use.

08.
arXiv (CS.CL) 2026-06-16

Bridging the Usability Gap: Lessons from Interpreting Studies for Machine Interpreting Design

Machine interpreting (MI), the live, real-time branch of speech translation, has achieved remarkable progress on standard benchmarks, with some systems approaching human parity on textual fidelity. Yet the user experience remains far inferior to interpreter-mediated communication, revealing what we term the accuracy illusion: systems that appear accurate on paper but fail in practice to support smooth, goal-oriented interaction. This paper defines MI as a distinct subfield of speech translation, with its own characteristics and the need for evaluation methods grounded in communicative effectiveness rather than isolated fidelity metrics. Drawing on insights from interpreting studies, we identify critical dimensions of professional interpreting practice that are overlooked by current systems, and consolidate them into three interdependent design priorities for future MI: agency (context-sensitive initiative and repair), grounding (multimodal and discourse-level situational awareness), and experience (adaptive improvement through real interaction). Together, these priorities chart a path toward closing the usability gap and enabling systems that can sustain authentic multilingual communication in real time.

09.
arXiv (CS.LG) 2026-06-16

Closing the Approximation Gap in Simulation-free Latent SDEs

arXiv:2606.16138v1 Announce Type: cross Abstract: Recovering dynamical systems from noisy observations is a recurring challenge across scientific domains, including neuroscience and physics. Latent stochastic differential equations (SDEs) address this by modeling the system as an unobserved state that evolves according to a learnable SDE and generates the observations. Variational inference (VI) provides a tractable objective for fitting latent SDEs. Traditional VI algorithms evaluate this objective by numerical simulation over a time discretization, trading fidelity for computational cost. A recent class of algorithms, simulation-free VI, sidesteps this tradeoff by parameterizing the posterior through its instantaneous marginals rather than its drift. In this work, we show that the efficiency of existing simulation-free VI algorithms comes at a price: their parameterizations restrict the approximate posterior to a subset of the SDEs available to simulation-based methods, degrading posterior inference and parameter learning. We propose Helmholtz-SDE, a simulation-free VI algorithm that closes this gap by optimizing over path laws compatible with a prescribed collection of marginals. Helmholtz-SDE recovers dynamics more faithfully than prior simulation-free methods, with the largest gains under high posterior uncertainty. It further matches the performance of simulation-based VI at a fraction of the runtime.

10.
arXiv (CS.CL) 2026-06-19

The ACUTE Protocol: Operationalizing Language Model Activations for Better Calibration, Utility, and Trust

As language models improve and become increasingly deployed to solve a variety of tasks, trustworthiness becomes essential. Calibration is a good proxy for trust: well-calibrated confidence estimates help inform the risk versus reward tradeoff when trusting a specific model output. Unfortunately, even as models improve, they remain poorly calibrated, often biasing towards overconfidence. Additionally, calibration can be gamed: a policy that always predicts the base rate is perfectly calibrated, but completely uninformative. To resolve this, we develop a new metric, expected utility renormalized by the oracle (EURO), that balances calibration and informativeness. We also propose a general-purpose activation-based confidence, utility, and trust estimation protocol (ACUTE) to appropriately adjudicate uncertainty. The ACUTE protocol provides flexible, sample-efficient, and compute-efficient confidence estimators for 3 tasks including multiple choice question answering, tool-calling, and scientific document summarization across 6 models from 4 model families. ACUTE outperforms strong baselines on EURO, while maintaining low calibration error. Taken together, our work shows that equipping LLMs with the ACUTE protocol can improve calibration, utility, and trustworthiness in numerous settings.

11.
arXiv (CS.CL) 2026-06-11

T2MM: An LLM Supported Architecture For Inquiry-Based Modeling

Model Construction is a foundational practice in science learning that relies on visualization and interactivity. Large Language Models, increasingly augmented with multimodal capabilities, have been integrated in education contexts to support learning. However, these tools lack visual interactivity that is required by some learning contexts. We introduce Text to Multimodal Model (T2MM), a robust, dynamic LLM supported architecture that assists in model construction within the open inquiry ecology-based modeling software Virtual Experimental Research Assistant (VERA). T2MM accounts for the current context of the learner's model and creates interactive models, rather than static images, enabling the model to remain responsive to manual adjustment. To measure technical feasibility, we evaluate T2MM through a custom procedurally generated dataset of natural language learner modeling requests and target models within the VERA system. T2MM outperforms a baseline model generation architecture implemented through LLM-supported full code generation, common in the literature, across all measured success metrics. Our contribution not only outlines LLM integration into a inquiry-based learning modeling tool, but also describes a possible architecture through which more interactive multimodal LLM tools can be created.

12.
arXiv (CS.LG) 2026-06-19

Self-Adaptive Scale Handling for Forecasting Time Series with Scale Heterogeneity

arXiv:2606.20010v1 Announce Type: new Abstract: Current time series forecasting (TSF) research predominantly focuses on scale-homogeneous data, where different time series share similar numerical magnitude ranges. However, in real-world industrial scenarios such as financial product sales, different time series often differ by orders of magnitude (scale heterogeneity). Since these series share similar temporal patterns, joint modeling is desirable for better data utilization, yet existing scaling methods either compress low-scale signals (global normalization) or destroy semantic discriminability and amplify inverse-scaling errors (window-based scaling). This paper proposes a self-Adaptive Scale-handling (AS) module that learns adaptive scale factors tailored to each input, preserving semantic discriminability while reducing inverse-scaling errors. AS consists of Scale Calibrating (SC), which calibrates prior mean scaling factors through neural networks, and Scaling Selection (SS), which decides whether to apply calibration or retain the original factor, avoiding over-calibration. Experiments on real-world fund sales datasets from Ant Fortune and Alipay show that AS seamlessly integrates into popular TSF models and consistently improves their performance. The code and dataset are available at the link https://github.com/Meteor-Stars/ASTSF.

13.
medRxiv (Medicine) 2026-06-22

Integration of lung tissue proteomics and genome-wide association data to identify lung cancer susceptibility proteins and potential drug targets

Background: Proteins directly impact disease development and act as drug targets. Therefore, we integrated genomic and lung tissue proteomics data to identify lung cancer susceptibility proteins, elucidating genetic mechanisms and candidate drug targets. Method: We profiled the proteome and genome in non-neoplastic lung tissue from 200 lung cancer patients. Using this data, we constructed genetic models to predict abundance across the proteome in lung tissue. We applied these models to genome-wide association study (GWAS) data from 55,174 lung cancer cases and 1,294,174 controls to evaluate their associations with the risk of lung cancer, overall and by major histological subtypes. Bayesian colocalization and Mendelian randomization (MR) analyses were used to prioritize putative causal proteins, which were cross-referenced with three main drug-protein databases to identify potential therapeutic targets. Results: We identified 29 proteins associated with lung cancer risk at a false discovery rate < 5%, including 25 for overall lung cancer, two (AQP3 and IL18) specifically for adenocarcinoma, and another two (HMGN2 and HLA-DMB) for squamous cell carcinoma. Of them, genes encoding 17 proteins reside at least 2Mb away from any known GWAS risk loci, including 14 for overall lung cancer (HYI, GPX1, GMPPB, DSP, HDDC2, MTCH2, SUOX, JMJD7, PDIA3, IL16, IQGAP1, SULT1A2, ARHGAP27, and TYMP) and three for subtypes (AQP3, IL18, and HMGN2). Among the 12 proteins located within the known risk loci, EPHX2, CLDN18, PSMD5, and CYP2S1 proteins showed an association independent of the proximal GWAS-identified lead variant. Colocalization and/or MR analysis suggested 11 potential causal proteins. Five of these candidate causal proteins (DSP, CLDN18, IQGAP1, IL18 and TYMP) are targeted by nine drugs already approved by the FDA or in phase III trials. Conclusion: Our study identified novel lung cancer susceptibility proteins and potential drug targets, offering valuable insights into lung cancer biology and future translational utilities.

14.
arXiv (CS.CV) 2026-06-16

Stepwise Token Selection for Efficient Multimodal Large Language Models

In multimodal large language models (MLLMs), inference cost is largely dominated by the visual token prefix rather than the language backbone, making token reduction a key factor for improving efficiency. Existing approaches typically assign independent importance scores to visual tokens and retain a fixed number of top-ranked tokens, implicitly assuming token independence and a uniform compression ratio across inputs. In this work, we reformulate visual token pruning as a sequential decision-making process. Specifically, we introduce a pointer-style selection mechanism that iteratively chooses informative tokens, conditioning each decision on previously selected ones, and dynamically determines when to stop via a learned termination action. This enables joint optimization of both the selected subset and its size. To enable end-to-end training under standard language modeling objectives, we design a differentiable relaxation based on a variance-preserving noise interpolation scheme, allowing gradients to propagate through the discrete selection process. Extensive experiments on LLaVA-v1.5-7B and Qwen2.5-VL-7B demonstrate that our approach consistently outperforms fixed-ratio baselines across different compression levels. Under aggressive pruning that removes 88.9% of visual tokens, our method preserves 94.6% of the original accuracy while achieving a 1.88x speed-up in prefill latency.

15.
arXiv (CS.CV) 2026-06-16

3D Classification of Paramagnetic Rim Lesions in Multiple Sclerosis via Asymmetric QSM-FLAIR Modeling

Paramagnetic rim lesions (Rim$^+$) identified on susceptibility-sensitive MRI have recently emerged as a specific biomarker of chronic active inflammation in Multiple Sclerosis (MS) and are associated with long-term disability progression. However, susceptibility imaging and expert interpretation remain limited to specialized centers, visual assessment is time-consuming and variable, and the low prevalence of Rim$^+$ lesions poses severe class imbalance challenges for automated analysis. We propose a 3D multimodal deep learning framework for lesion-level Rim$^+$/Rim$^-$ classification from Quantitative Susceptibility Mapping (QSM) and FLAIR MRI. The architecture explicitly models modality asymmetry by treating QSM as the primary susceptibility-driven signal and conditioning it with FLAIR-derived structural context. To improve robustness under limited data, we employ self-supervised multimodal pretraining followed by supervised fine-tuning with contrastive regularization. The method was evaluated on a clinically acquired cohort of 88 people with MS with expert lesion annotations as reference standard. Results highlight improved performance compared to prior architectures, supporting the effectiveness of asymmetric multimodal modeling for automated chronic active lesion identification.

16.
arXiv (CS.AI) 2026-06-16

ATOM-Bench: A Real-World Benchmark for Atomic Skills and Compositional Generalization in Manipulation Policies

arXiv:2606.16826v1 Announce Type: cross Abstract: Generalist manipulation policies are increasingly presented as foundation models for robotic control, but their real-world generalization remains difficult to diagnose. A policy may succeed on demonstrated tasks while still failing to execute fine-grained atomic skills or recombine learned skills in new task structures. We introduce ATOM-Bench, a real-world benchmark for evaluating both atomic skills and compositional generalization in manipulation policies. ATOM-Bench factorizes tabletop manipulation into motor atoms and instruction atoms, and contains 30 atomic tasks and 24 held-out compositional tasks across paired single-arm and dual-arm robot tracks. We collect 3,000 human demonstrations for atomic fine-tuning and release both the demonstration data and evaluation rollout data to support reproducible real-world evaluation. Policies are fine-tuned on atomic tasks and evaluated on both atomic skill acquisition and held-out compositional tasks. We further introduce Atomic Score (AS) and Compositional Failure Share (CFS) to distinguish failures caused by weak atomic skills from failures caused by limited compositional reuse. Through 2,700 physical rollouts on five representative manipulation policies, we find that current policies can acquire simple instruction-grounding skills, but still struggle with fine-grained motor atoms, counting, and logical filtering. More importantly, strong atomic performance does not reliably transfer to held-out compositional tasks. ATOM-Bench provides a diagnostic testbed for studying whether failures arise from weak motor execution, poor instruction grounding, or limited compositional reuse.

17.
arXiv (CS.CL) 2026-06-15

SIMMER: Benchmarking Latent Failures in LLM Executable Planning with a World Model

Large language models (LLMs) are increasingly deployed as planners for autonomous agents in household environments. While existing benchmarks evaluate whether LLM-generated plans execute successfully, they overlook a critical type of failure: latent failures. Unlike immediate failures that trigger instant feedback at execution time and enable timely correction, latent failures do not immediately halt plan execution but silently compromise goal achievement. In severe cases, they cause irreversible harm. To address this gap, we introduce SIMMER, a benchmark for evaluating latent failures in LLM planning through a human-curated symbolic world model grounded in the kitchen domain. SIMMER defines a world model comprising 77 actions, 262 unique objects, and approximately 46,800 possible interactions that are semantically realistic, derived from real-world cooking scripts. It then leverages a state machine executor that validates plans against the world model and detects immediate precondition violations, latent hazards, and irreversible failures. Experiments across six LLMs show that even frontier models achieve at most 17% error-free plans. Moreover, up to 56% of plans contain latent failures, the majority of which lead to irreversible consequences. We further demonstrate that explicit state reasoning via counterfactual foresight simulation can reduce latent failures by up to 72% and irreversible cases by up to 75%, suggesting a promising direction for more robust LLM planners.

18.
arXiv (CS.CV) 2026-06-16

Faithful Action-unit Causal Reasoning for Counterfactually Faithful Emotion Explanations

Multimodal models can name the action units (AUs) behind a facial emotion, but their AU->emotion rationales are typically plausible rather than faithful: nothing forces the AUs a model invokes to be the AUs that actually drive its prediction. We cast AU->emotion reasoning as a counterfactual-consistency problem between the rationale, the label, and a structural AU->emotion causal graph G, and propose FACR, which grounds the reasoner in an independently induced, polarity-aware G and trains a counterfactual-faithfulness objective: a do-intervention on an AU that G marks causal for a class must move the prediction, while one it marks irrelevant must leave it unchanged. Faithfulness is thereby both trainable and measurable through a matching interventional metric, which we evaluate against a known causal structure, the PSPI pain-AU composition, as no existing affective-reasoning benchmark allows. We are explicit that this metric tests fidelity to the supplied structure rather than its rediscovery: it asks whether the trained reasoner invokes the AUs the structure marks causal, on held-out subjects and a second dataset. Under subject-independent evaluation on UNBC-PAIN, the objective raises the agreement between the invoked AUs and the PSPI composition from a no-objective baseline of 0.08 to 0.57, at a small detection cost; an unfaithfulness control attributes the gain to the objective. On a cross-dataset emotion transfer, the objective likewise raises fidelity to G on a seven-class task (0.50 to 0.84). Finally, we attach a language verbalizer and extend the audit to the generated text: biasing each action unit's emission by its latent activation makes the rationale faithful by construction, so that ablating an AU removes it from the explanation, a property that transfers to a second language-model backbone, whereas a freely generated rationale is unfaithful.

19.
arXiv (CS.CL) 2026-06-11

M4FC: a Multimodal, Multilingual, Multicultural, Multitask Real-World Fact-Checking Dataset

Existing real-world datasets for multimodal fact-checking have multiple limitations: they contain few instances, cover on only one or two languages, focus only on one task, or rely on external news article sets for sourcing true claims. To address these shortcomings, we introduce M4FC, a new real-world dataset comprising 4,982 images paired with 6,980 claims. The images, verified by professional fact-checkers from 22 organizations, represent a diverse range of cultural and geographic contexts. Each claim is available in one or two out of ten languages. M4FC spans six multimodal fact-checking tasks: visual claim extraction, claimant intent prediction, fake image detection, image contextualization, location verification, and verdict prediction. We provide baseline results for all tasks and analyze how combining intermediate tasks affects verdict prediction performance. We make our dataset and code publicly available.

20.
arXiv (CS.AI) 2026-06-16

Fusion is not one-size-fits-all: Cross-Modal Representation Alignment for Time-to-Event Modeling

arXiv:2606.15038v1 Announce Type: new Abstract: Accurate time-to-event (TTE) prediction from multimodal clinical data remains challenging due to modality imbalance and distribution shift. We introduce a foundation model-driven framework for cross-modal representation alignment between CT imaging and longitudinal EHR data, designed to generalize across tasks and institutions. CT and EHR modalities are encoded independently using domain-specific foundation models and aligned in a shared latent space through four principled fusion strategies: late fusion, contrastive alignment, cross-attention, and co-attention. We evaluate two clinically distinct TTE tasks: pulmonary embolism (PE) mortality and cardiovascular disease (CVD) outcomes, on large-scale multi-institutional cohorts (PE: N=3,099 train; 1,098 internal; 435 external; CVD: N=2,951 train; 837 internal; 682 external). Fusion consistently improves concordance index by 1.5-5.4% over unimodal baselines when modalities contribute comparably. Overall, contrastive multimodal fusion, particularly with CLMBR representations, provided the most consistent and statistically robust improvements, especially for PE mortality prediction. For MACE, cross-attention (one-hot) achieved the highest internal performance and image-guided co-attention achieved the best external performance. We therefore introduce a generalizable foundation model-based cross-modal alignment framework and provide the first systematic analysis of fusion behavior under modality imbalance in TTE prediction. Our results establish task-aware multimodal alignment as a necessary design principle for robust generalization and scalable clinical deployment.

21.
arXiv (CS.CL) 2026-06-15

Beyond Perplexity: UTF-8 Validity in Byte-aware Language Models

Byte-level tokenization enables language models to handle any Unicode input, but models can generate invalid UTF-8 sequences when encountering rare or unseen characters. We investigate the relationship between training scale and UTF-8 generation reliability with a 355M parameter model trained on 80B tokens from a balanced multilingual corpus of English, Japanese, Korean, and Chinese. We introduce multiple evaluation protocols that isolate UTF-8 structural validity from language modeling. UTF-8 validity convergence lags perplexity by a roughly a factor of two: perplexity stabilizes after 2.1B tokens, but UTF-8 validity requires 4.2B tokens. In context-free generation, rare characters achieve higher structural validity than common characters, suggesting over-specialization of frequent character representations. Through experiments, we observed that reliable UTF-8 generation is a distinct capability requiring evaluation beyond perplexity.

22.
medRxiv (Medicine) 2026-06-11

Population-scale detection of methylation outliers from long-read genome sequencing

Background: Aberrant DNA methylation can mediate the functional effects of rare genetic variation and contribute to imprinting disorders, repeat expansion diseases, and other pathogenic regulatory mechanisms. Long-read sequencing technologies now enable genome-wide detection of CpG methylation alongside genetic variation from a single assay. However, methods for systematic identification and interpretation of methylation outliers from long-read sequencing data remain limited. Methods: We developed METAFORA, a computational workflow for detecting methylation outlier regions from PacBio and Oxford Nanopore long-read sequencing data. METAFORA constructs population-level methylation references, segments the genome into correlated CpG blocks, infers technical and biological sources of variation through hidden factor estimation, models uncertainty due to variable depth sequencing, and computes covariate-adjusted methylation outlier scores for individual samples. We applied METAFORA across large long-read sequencing cohorts and integrated methylation outliers with multi-omic data. METAFORA is implemented as a snakemake workflow available at https://github.com/tjense25/METAFORA. Results: METAFORA identified methylation outlier regions associated with rare structural variants, tandem repeat expansions, and imprinting abnormalities. We found outlier regions were enriched for molecular outliers across transcriptomic and chromatin accessibility datasets, supporting their functional relevance in gene regulation. In a representative case, METAFORA identified an imprinting defect affecting the GNAS locus associated with an STX16 deletion. Conclusions: METAFORA enables scalable detection and interpretation of methylation outliers from long-read sequencing data and provides a framework for integrating epigenetic outliers with genomic and multi-omic analyses. These approaches may improve interpretation of rare regulatory variation and support discovery of clinically relevant epigenetic abnormalities in genomic medicine.

23.
bioRxiv (Bioinfo) 2026-06-12

Generalisable tissue-wide molecular reconstruction from histology

Spatial transcriptomics technologies measure gene expression within intact tissues but remain difficult to scale across large tissue sections and patient cohorts. Consequently, many studies rely on tissue microarrays (TMAs) or sparse spatial profiling designs, where molecular measurements are available for only limited tissue regions and are often generated using heterogeneous gene panels. Existing H&E to spatial gene expression prediction methods remain challenged by sparse molecular measurements, partially overlapping gene panels and tissue-wide reconstruction across heterogeneous spatial datasets. Here, we present GHIST+, a framework for tissue-wide reconstruction of single-cell molecular states from H&E histology. GHIST+ integrates cellular morphology, local tissue context and shared tissue representations to extend sparse molecular measurements into tissue-wide molecular maps across heterogeneous spatial datasets. Across multiple cancer types and GTEx breast tissues, GHIST+ reconstructs biologically meaningful tissue-wide molecular organisation from sparse TMA-derived measurements while preserving spatial tissue structure, cell-type organisation and age-associated tissue states across cancer and non-cancer settings. GHIST+ establishes a scalable framework for transforming sparse spatial profiling experiments into tissue-wide molecular maps, enabling cohort-scale molecular reconstruction from routine histology under heterogeneous spatial transcriptomic settings.

24.
arXiv (math.PR) 2026-06-11

Large deviations for marked sparse random graphs with applications to interacting diffusions

arXiv:2204.08789v2 Announce Type: replace Abstract: We consider the empirical neighborhood distribution of marked sparse Erdős-Rényi random graphs, obtained by decorating edges and vertices of a sparse Erdős-Rényi random graph with i.i.d. random elements taking values on Polish spaces. We prove that the empirical neighborhood distribution of this model satisfies a large deviation principle in the framework of local weak convergence. We rely on the concept of BC-entropy introduced by Delgosha and Anantharam~(2019) which is inspired on the previous work by Bordenave and Caputo~(2015). Our main technical contribution is an approximation result that allows one to pass from graph with marks in discrete spaces to marks in general Polish spaces. As an application of the results developed here, we prove a large deviation principle for interacting diffusions driven by gradient evolution and defined on top of sparse Erdős-Rényi random graphs. In particular, our results apply for the stochastic Kuramoto model. We obtain analogous results for the sparse uniform random graph with given number of edges.

25.
arXiv (CS.CL) 2026-06-16

Weaving Multi-Source Evidence for Biomedical Reasoning: The BioMedHop Benchmark and BioWeave Framework

Biomedical question answering (QA) increasingly requires reasoning over interacting entities, where supporting evidence is scattered across biomedical knowledge graphs, literature documents, and web-accessible resources. However, existing biomedical QA benchmarks mainly focus on exam-style knowledge, literature comprehension, or short-range multi-hop inference, leaving source-conditioned graph reasoning and evidence topology construction underexplored. To fill this gap, we introduce BioMedHop, a multi-source graph-grounded benchmark for evaluating biomedical reasoning over structured evidence topologies. BioMedHop contains 10,045 instances across KG, document, web, and hybrid evidence settings, covering shared-neighbor matching, intersection reasoning, path-based reasoning, and counting, with option-based, open-ended, and numeric count renderings. To support this benchmark, we further propose BioWeave, a source-aware reasoning framework that retrieves biomedical KG paths, gathers supporting clues from documents and web sources, assembles them into a unified evidence graph, and verifies answers through entity-level evidence support. Comprehensive experiments show that BioWeave achieves the best overall performance among compared methods on BioMedHop, outperforming the strong hybrid baseline ToG-2 by 10.5% in the overall average. Moreover, BioWeave consistently improves different LLM backbones and enables smaller models, such as Qwen3-4B, to achieve reasoning performance comparable to GPT-4-Turbo.