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01.
arXiv (CS.AI) 2026-06-11

Graph2Idea:Retrieval-Augmented Scientific Idea Generation with Graph-Structured Contexts

arXiv:2606.09105v3 Announce Type: replace Abstract: Generating novel, feasible, and high-quality research ideas is an important yet challenging task in scientific discovery. Recent Large Language Model (LLM)-based methods often ground idea generation with retrieved literature, but the retrieved evidence is usually provided as flat text, such as titles, abstracts, or summaries. Such flat contexts may contain redundant or weakly relevant information, while making cross-paper relations among problems, methods, mechanisms, and findings difficult to identify and trace. To address this challenge, we propose Graph2Idea, a knowledge graph-guided framework for retrieval-augmented scientific idea generation.Graph2Idea first retrieves papers according to the input topic, transforms them into structured knowledge triples, and dynamically constructs a target-centered knowledge graph to make literature relations explicit. It then extracts compact graph-derived contexts that retain target-relevant relational evidence while reducing noisy textual input. Based on these contexts, a two-stage generation process first identifies promising research directions and then guides the LLM to synthesize candidate ideas from graph-grounded evidence. Experiments on a scientific idea generation benchmark show that Graph2Idea outperforms representative baselines under the automatic evaluation protocol. Compared with the strongest baseline scores, it improves Novelty from 0.45 to 0.52, Quality from 0.24 to 0.29, and Feasibility from 0.22 to 0.28. These results suggest that graph-structured evidence helps LLMs generate research ideas through more explicit, compact, and traceable recombination of prior scientific knowledge.

02.
arXiv (CS.AI) 2026-06-16

Metric Match: A Subset Selection Approach to Evaluating LLM Judge Reliability

arXiv:2606.15029v1 Announce Type: new Abstract: LLM judges are used to reduce the need for costly human labor in evaluating open-ended text generation. However, the reliability of these judges depends critically on their alignment with human raters – a property that itself depends on costly human annotations. In this work, we develop a method (Metric Match) for estimating correlation-based reliability metrics of LLM judges from limited annotations. Metric Match selects a subset of samples for human annotation such that the subset matches the population reliability metric with respect to acquired synthetic labels. We empirically show that Metric Match achieves a win-rate of 0.838 against random subset selection across four different correlation metrics and 15 datasets, with an 18.7% decrease in average estimation error and reduces annotation needs by 32.5%. We provide a cost model and highlight a medical case study where our method saves $1,041.67 compared to random selection for expert annotation. Further, we shift our task from reliability estimation to reliability classification of whether a given judge is above a deployment threshold, outperforming random selection with Metric Match. All project code is publicly available, and we additionally provide an installable package for ease of use.

03.
arXiv (CS.LG) 2026-06-19

Recurrent neural networks approximate continuous functions

arXiv:2606.20325v1 Announce Type: new Abstract: Classical approximation theorems ask for a new neural network whenever the target accuracy is improved. This paper studies the opposite possibility: can the network be chosen once and for all, and can accuracy be bought only by letting it run longer? We prove that this is possible for every continuous function on [-1,1]. More precisely, each such function is uniformly approximated by the time evolution of a single ReLU recurrent neural network with fixed weights and fixed hidden dimension. The mechanism behind the construction is a new intermediate model, the Turing machine with neural units (TMNU). This model retains the algorithmic freedom needed to implement polynomial approximation schemes, while remaining rigid enough to be simulated by RNNs with explicit bounds on hidden dimension and weight magnitude. The resulting convergence rates reflect the underlying polynomial approximation rates. We complement the construction with minimax lower bounds showing that runtime is not merely a proof artifact, but an unavoidable resource in this fixed-network approximation paradigm.

04.
arXiv (CS.CV) 2026-06-18

Splaxel: Efficient Distributed Training of 3D Gaussian Splatting for Large-scale Scene Reconstruction via Pixel-level Communication

3D Gaussian Splatting (3DGS) enables high-fidelity and real-time 3D scene reconstruction, but scaling training to large-scale scenes requires optimizing hundreds of millions of Gaussians across multiple GPUs. Existing distributed approaches either partition scenes into isolated regions, causing global inconsistency, or rely on global Gaussian-level exchanges, which lead to substantial growth in inter-GPU communication and quickly dominate iteration time. We propose Splaxel, a communication-efficient distributed 3DGS training framework based on pixel-level local rendering and global composition. Instead of synchronizing Gaussians, each GPU renders its local subset and exchanges only partial pixel values, maintaining mathematical consistency while keeping communication cost stable as the scene size increases. Splaxel further reduces pixel-level redundancy through geometric and transmittance visibility prediction and improves GPU utilization via conflict-free camera-view consolidation. Evaluated on large-scale datasets with up to 120M Gaussians, Splaxel achieves up to 7.6$\times$ speedup over the state-of-the-art distributed 3DGS framework while preserving high reconstruction quality.

05.
arXiv (CS.CL) 2026-06-11

I Understand How You Feel: Enhancing Deeper Emotional Support Through Multilingual Emotional Validation in Dialogue System

Emotional validation - explicitly acknowledging that a user's feelings make sense - has proven therapeutic value but has received little computational attention. Emotional validation in dialogue systems can be decomposed into (i) validating response identification, (ii) validation timing detection, and (iii) validating response generation. To support research on all three subtasks, we release M-EDESConv, a 120k English-Japanese multilingual corpus created through hybrid manual and automatic annotation, and M-TESC, a multilingual spoken-dialogue test set. For timing detection, we propose MEGUMI, a Multilingual Emotion-aware Gated Unit for Mutual Integration, that fuses frozen XLM-RoBERTa semantics with language-specific emotion encoders via cross-modal attention and gated fusion. MEGUMI shows superior performance on both the M-EDESConv and M-TESC datasets, both objectively and subjectively. Finally, our EmoValidBench benchmarks of GPT-4.1 Nano and Llama-3.1 8B indicate that current LLMs generate contextually similar and diverse validating responses, but emotional understanding remains a major area for improvement. Project page: https://github.com/zihaurpang/Multilingual-Emotional-Validation

06.
arXiv (CS.AI) 2026-06-19

Process-Verified Reinforcement Learning for Theorem Proving via Lean

arXiv:2606.20068v1 Announce Type: new Abstract: While reinforcement learning from verifiable rewards (RLVR) typically has relied on a single binary verification signal, symbolic proof assistants in formal reasoning offer rich, fine-grained structured feedback. This gap between structured processes and unstructured rewards highlights the importance of feedback that is both dense and sound. In this work, we demonstrate that the Lean proof assistant itself can serve as a symbolic process oracle, supplying both outcome-level and fine-grained tactic-level verified feedback during training. Proof attempts are parsed into tactic sequences, and Lean's elaboration marks both locally sound steps and the earliest failing step, yielding dense, verifier-grounded credit signals rooted in type theory. We incorporate these structured rewards into a GRPO-style reinforcement learning objective with first-error propagation and first-token credit methods that balances outcome- and process-level advantages. Experiments with STP-Lean and DeepSeek-Prover-V1.5 show that tactic-level supervision outperforms outcome-only baselines in most settings, delivering improvements on benchmarks such as MiniF2F and ProofNet. Beyond empirical gains, our study highlights a broader perspective: symbolic proof assistants are not only verifiers at evaluation time, but can also act as process-level reward oracles during training. This opens a path toward reinforcement learning frameworks that combine the scalability of language models with the reliability of symbolic verification for formal reasoning.

07.
arXiv (CS.CL) 2026-06-18

Learning User Simulators with Turing Rewards

Learning to simulate human users in interactive settings could advance the training of agent assistants, evaluation of personalization systems, research in the social sciences, and more. Existing approaches generally do so by training a large language model (LLM) to match a single ground truth response, either by maximizing the log probability or by using a similarity reward. We instead propose {Turing-RL}: a Turing-Test-based reinforcement learning approach for training user simulator models. {Turing-RL} uses a discriminative Turing reward with an LLM judge to score how indistinguishable a generated response is from the real user's given the user's history, and the user simulator LLM learns to produce responses indistinguishable from what the user could have said with such rewards. Across two different domains–conversational chat and Reddit forum discussion–we find that {Turing-RL} consistently outperforms baseline methods on both LLM and human evaluation metrics. Our study suggests that optimizing for indistinguishability, rather than response matching, is effective for learning user simulators.

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

GridVQA-X: A Framework for Evaluating Multimodal Explainability Methods

With the increasing development of Vision-Language Models, it becomes imperative that their predictions are readily explainable to relevant stakeholders. However, the field of explainability has not kept pace with the multimodal surge. While recent Multimodal Explainable AI (MxAI) methods generate explanations to attribute the interaction between different modalities, current evaluation protocols lack the ground truth required to distinguish between true cross-modal reasoning (e.g., spatial composition) and shallow cross-modal shortcuts (e.g., Bag-of-Words attribute matching). It remains unknown whether MxAI methods faithfully capture synergistic interactions or merely hallucinate reasoning on models acting as simple feature detectors. In this paper, we introduce GridVQA-X, the first diagnostic framework specifically designed to evaluate cross-modal explainability. Unlike natural datasets, GridVQA-X leverages a closed-world synthesis logic to generate unique, mathematically guaranteed explanations. We utilize this controlled environment to train paired ground-truth models on identical architectures: $M_{pure}$, which learns robust spatial-relational reasoning and $M_{spur}$, which is structurally forced to rely on cross-modal shortcuts. This behavioral divergence creates a rigorous testbed: a faithful explainer must report distinct reasoning pathways for each model. Our findings reveal that widely used methods fail to distinguish between models relying on genuine spatial-relational reasoning and those exploiting cross-modal shortcuts, highlighting a critical gap in capturing true cross-modal synergy and misrepresenting how multimodal models actually make decisions.

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

BadWorld: Adversarial Attacks on World Models

Visual world models (VWMs) synthesize interactive, action-conditioned rollouts from a single context image. However, it remains an open question how robust these models are to adversarial perturbations. Standard adversarial attacks fail to assess this vulnerability because attackers lack ground-truth future videos and cannot predict subsequent user controls. We introduce BadWorld, a label-free adversarial framework tailored for autoregressive VWMs that systematically overcomes both constraints. First, to bypass the need for future supervision, we propose a self-supervised velocity attack that directly disrupts the early denoising dynamics of the model. Second, to ensure the attack generalizes across unpredictable user actions, we formulate a trajectory-adaptive bi-level optimization that actively mines hard control sequences to forge control-agnostic perturbations. Evaluated on representative VWMs with continuous and discrete controls, BadWorld exposes severe structural fragility. Visually indistinguishable adversarial images reliably trigger catastrophic degradation in future rollouts, leading to incomplete denoising, structural collapse, and control inconsistency. These findings reveal critical risks for deploying VWMs in safety-critical systems while highlighting a practical mechanism for privacy protection.

10.
arXiv (CS.LG) 2026-06-17

Recursive Scaling in Masked Diffusion Models

arXiv:2606.18022v1 Announce Type: new Abstract: Masked diffusion models (MDMs) have recently emerged as a promising paradigm for sequence generation. Scaling MDMs is conventionally achieved by increasing the parameter count or the number of denoising steps. We introduce Recursive Masked Diffusion Models (R-MDMs), which add recursive depth as a third scaling axis by repeatedly applying the same denoising transformer within each diffusion step. Recursion enables iterative refinement of the output through parameter reuse, increasing effective model depth without increasing parameter count. Across structured generation tasks, including Sudoku and Countdown, we show that R-MDMs achieve substantially improved parameter efficiency: a model with $L$ recursive iterations often matches the performance of non-recursive baselines with roughly $L\times$ more parameters. Moreover, recursive refinement can partially substitute for additional denoising steps, allowing recursive models to reach the same generation quality with fewer forward passes at inference time. These results suggest that recursive depth is a practically useful scaling mechanism for MDMs, improving both parameter efficiency and the allocation of test-time compute.

11.
arXiv (CS.CV) 2026-06-18

Revealing Hidden Vulnerabilities in Autoencoders through Gradient Signal Restoration

Adversarial robustness of deep autoencoders (AEs) has received less attention than that of discriminative models, although their compressed latent representations induce ill-conditioned mappings that can amplify small input perturbations and destabilize reconstructions. Existing white-box attacks for AEs, which optimize norm-bounded adversarial perturbations to maximize reconstruction damage, often converge to suboptimal perturbations, thereby potentially overstating AE robustness. We show that this limitation is linked to vanishing adversarial loss gradients during backpropagation through ill-conditioned layers, associated with near-zero singular values in their intermediate weight matrices. To address this, we propose GRILL (Gradient Signal Restoration in Ill-Conditioned Layers), a framework designed to mitigate gradient degradation and improve the reliability of adversarial robustness evaluation in encoder-decoder architectures. GRILL is designed to mitigate adversarial gradient degradation during optimization, enabling attacks to better approximate high-distortion perturbations under fixed norm constraints. Through extensive experiments across multiple AE architectures, under both sample-specific and universal attacks, as well as standard and adaptive attack settings, we show that GRILL significantly increases attack effectiveness, thereby exposing vulnerabilities hidden by existing attack limitations. Beyond AEs, we provide preliminary evidence that modern multimodal encoder-decoder architectures exhibit similar vulnerabilities.

12.
arXiv (CS.LG) 2026-06-17

A 3D Isovist World Model – Revealing a City's Unseen Geometry and Its Emergent Cross-City Signature

arXiv:2606.03609v3 Announce Type: replace-cross Abstract: Embodied agents that navigate cities rely on world models that predict how their surroundings will change as they move. But for navigation, what matters is not what the buildings look like; it is where the agent can go. Most world models nonetheless predict appearance, learning how a scene looks rather than the space an agent can move through. Those that do target geometry, such as bird's-eye-view occupancy grids, flatten the three-dimensional environment onto a ground plane, discarding the above-ground and multi-level structure that shapes real navigation. What is missing is a predictive target that captures the navigable geometry an agent actually traverses, without photometric entanglement and without collapsing the third dimension. Our key idea is to model the open volume between buildings, the negative space, encoded as a 3D isovist: a spherical visibility-depth map recording the distance to the nearest surface in every direction. We introduce an embodied world model that predicts the next isovist from a short history of past isovists and a movement action. The prediction is formulated as a depth residual so the decoder inherits sharp building edges, trained with self-rollout scheduled sampling to keep corrupted context on the geometry manifold, and equipped with a persistent latent bird's-eye-view spatial map for cross-path consistency. Our central finding is emergent and unexpected: a single city-blind model trained on Manhattan and Paris develops a cross-city spatial signature, with city identity linearly decodable from its temporal latents far above single-frame baselines, so the signature lives in the learned dynamics rather than in appearance. The representation is lightweight, interpretable, and reproducible, offering a geometric substrate for spatial reasoning in embodied AI, robotics, and urban analysis, released with an open dataset and pipeline.

13.
arXiv (math.PR) 2026-06-17

Persistence diagrams of random triangular matrices over finite fields

arXiv:2606.17895v1 Announce Type: cross Abstract: Let us consider a random infinite lower triangular matrix, where the entries on and below the diagonal are i.i.d. uniform random elements of a fixed finite field. We investigate the evolution of the span of the first $n$ rows of this matrix as $n$ grows. Many properties of this evolving subspace can be captured with the help of the verbose persistence diagram, which is a standard tool in stochastic topology and topological data analysis. We give an explicit formula for the distribution of the persistence diagram. We prove a law of large numbers for the distribution of lifetimes. We also describe the fluctuations of the persistent Betti numbers.

14.
arXiv (quant-ph) 2026-06-17

Tunneling Dynamics and Time Delay in Electron Transport through Time-Dependent Barriers with Finite-Bandwidth Reservoirs

arXiv:2507.20649v2 Announce Type: replace-cross Abstract: We study a model system consisting of a tunneling barrier driven by an external harmonic field and coupled to two leads with finite bandwidth. Avoiding Floquet expansions, we derive simple expressions for the time-dependent tunneling current in the adiabatic regime. Our approach relates the barrier modulation to a measurable time delay in the steady-state periodic current. It provides a physically consistent definition of the tunneling time inside the barrier by subtracting the time delay associated with the leads from the total time delay. We find that the tunneling time always vanishes for wide/high barriers. Remarkably, the time delay persists even when the barrier becomes static, i.e., in the limit where the modulation frequency vanishes. This indicates that the time delay obtained through the introduction of an external periodic perturbation actually reflects an intrinsic property of the tunneling dynamics, rather than an effect of the external drive or of a particular system. We apply our results to the analysis of tunneling times in optical experiments and find good agreement with the experimental data.

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

A First-Principles Derivation of LLM Policy Optimization: From Expected Reward to GRPO and Its Structural Extensions

arXiv:2606.16733v1 Announce Type: new Abstract: Policy gradient algorithms for language models optimize the same objective $J(\theta) = \mathbb{E}*{\tau \sim p*\theta(\tau)}[R(\tau)]$, which has exactly two factors: the trajectory probability $p_\theta(\tau)$ and the reward $R(\tau)$. Every method from REINFORCE to PPO to GRPO and their descendants modifies one or both factors to address a specific failure in the preceding formulation. Existing surveys organize these methods by domain or chronology, which obscures the rationale behind each design choice and the precise location of its intervention within the gradient estimator. This survey revisits the landscape of LLM policy optimization from $J(\theta)$ on first principles and uses the trajectory side, induced by $p_\theta(\tau)$, and the reward side, induced by $R(\tau)$, as the two axes along which methods are located. It covers the path from REINFORCE and PPO to GRPO, as well as post-GRPO variants, Agentic RL, and GRPO-OPD. The resulting framework is unified, diagnostic, and extensible: it analyzes methods from a shared objective, identifies which side each method modifies and why, and applies the same trajectory and reward axes across these settings. Across these settings, the framework also exposes compound failures that no single-side fix resolves and that therefore require joint design of the trajectory side and the reward side. The boundary cases and coupled failures identified by this map mark where existing solutions run out and provide a principled starting point for designing the next generation of LLM policy optimization algorithms.

16.
arXiv (quant-ph) 2026-06-19

Local controllability of heralded quantum linear optics

arXiv:2606.19470v1 Announce Type: new Abstract: Photonic linear optical networks provide a versatile platform for quantum information processing and quantum state engineering. However, the set of states that can be generated using passive linear optics alone is fundamentally constrained by bosonic symmetries. Heralding, based on conditional measurements on auxiliary modes, is a widely used technique to overcome these limitations and effectively enlarge the set of accessible states. Despite the widespread use of heralding, it is often unclear how specific ancillary resources impact the overall reachability of the target space. In this work, we investigate the local controllability of photonic states in linear optical networks by analyzing the rank of the Jacobian of the output state with respect to the underlying unitary circuit, which provides a quantitative measure of the dimension of the accessible tangent space at a given configuration. Our analysis ranges from passive linear optics to heralded linear optics, where auxiliary resources and conditional measurements are included. Within this framework, we quantify how different resources enlarge the locally accessible state space beyond that of passive linear optics and determine the resources required for the Jacobian rank to reach its maximal value, thereby achieving full local controllability. As maximal local rank is a necessary condition for global reachability, our framework offers a systematic tool to assess and compare the accessible state space of measurement-based photonic architectures, and to establish practical criteria for the resources needed in high-dimensional quantum state engineering.

17.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

Authors:

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20–25% of individuals exhibited accelerated aging in a single cell type and 1–3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer’s Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience. The biological age of individual cell types can be evaluated using plasma proteomics, revealing diverse aging profiles across more than 40 cell types and links between the accelerated aging of specific cell types and disease.

18.
arXiv (quant-ph) 2026-06-11

Quantum Entanglement, Stratified Spaces, and Topological Matter: Towards Entanglement-Sensitive Langlands Data

arXiv:2601.13467v2 Announce Type: replace Abstract: Using the spinless Haldane model, we study the witness-filtered Berry curvature, quantum geometric tensor, and quantum Fisher information on the gapped strata of the parameter space and evaluate them through the Fukui-Hatsugai-Suzuki discretization. The filtered quantities isolate the part of the geometric response carried by sublattice coherence: they suppress contributions from regions where the occupied Bloch state is locally A/B-separable and emphasize regions where curvature and coherence coexist. We derive exact lattice identities, reconstruction formulas for the curvature-weighted coherence, and bounds relating the filtered quantum geometric tensor and quantum Fisher information to single-particle mode entanglement. Across the gap-closing stratum, the quantized response changes admit a natural description in terms of Hecke modifications. We elicit a corresponding Langlands viewpoint – not as a full correspondence, but as an organizational principle and as the mathematical shadow of these physical geometric constructions.

19.
arXiv (CS.CL) 2026-06-16

Not What, But How: A Framework for Auditing LLM Responses across Positioning, Generalization, Anthropomorphism, and Maxims

Large language models (LLMs) are being increasingly used to answer subjective, information-seeking questions, where users are sensitive to how responses are communicated, not just whether the answers are correct. Existing LLM evaluations for subjective cultural queries largely focus on factual correctness, ignoring how the response is framed. To this end, we introduce FRANZ, an automated FRAmework for respoNse characteriZation to conduct communicative audit of LLM responses along four dimensions: cultural positioning, use of generalizing language, anthropomorphic cues, and adherence to conversational maxims. To enable this evaluation, we contribute SQUARE - a corpus of 376k subjective questions sourced from 57 subreddits, and mapped to 7 countries and 19 question categories. We demonstrate FRANZ's applicability by scoring responses from three open-weight LLMs. We observe that LLMs show statistically significant differences in the frequency with which they employ each response characteristic. Unlike single-dimensional audits, FRANZ reveals that insider positioning and anthropomorphism are positively coupled, with the degree of coupling varying by country, providing a diagnostic lens for identifying framing divergences.

20.
arXiv (CS.CV) 2026-06-12

Magnifying What Matters: Attention-Guided Adaptive Rendering for Visual Text Comprehension

Visual Text Comprehension (VTC) renders text into images for a vision-language model (VLM) to read, sidestepping LLM context-window limits and powering applications from long-page OCR to multi-page memory QA. Yet existing VTC pipelines treat rendering and layout as a fixed, content-agnostic preprocessing step and offer little mechanistic understanding of how VLMs internally process visualized text. Through a focused empirical study on VTC QA tasks, we reveal that VLMs exhibit a localization-without-utilization regime: evidence-localizing attention emerges sharply in the middle-to-late layers and is largely decoupled from answer correctness, yet simply enlarging the localized spans on the rendered page recovers a large fraction of the failures. Building on these observations, we propose AGAR (Attention-Guided Adaptive Rendering), a training-free, model-agnostic method that leverages a VLM's own middle-to-late layer attention to identify the top-K important visual patches, maps them back to word spans, and re-renders the page with those spans enlarged before re-inferring the answer. Extensive experiments across nine VTC benchmarks (short-form, long-context, and multi-page memory QA) and four VLM backbones show that AGAR (i)consistently improves off-the-shelf VLMs as a plug-and-play enhancement, (ii)composes with VLM post-training to yield further gains, and (iii)remains robust under both visual- and text-side input degradation.

21.
arXiv (CS.CV) 2026-06-19

SpatialSV: Internalizing Interpretable 3D Spatial Awareness in MLLMs via Task-Oriented Visual Supervision

Unlocking the spatial intelligence of multimodal large language model (MLLMs) is crucial for understanding and interacting with the 3D world. Prevailing approaches typically inject spatial priors via external tools, which impose significant inference overhead, or rely on latent feature distillation, which remains uninterpretable and lacks fine-grained geometric constraints. To address these issues, we propose SpatialSV, a framework designed to internalize robust 3D spatial awareness within MLLMs while simultaneously offering inherent interpretability. Deviating from passive feature imitation, SpatialSV employs task-oriented visual supervision, compelling the model to actively lift its 2D visual features into explicit 3D representations, including depth maps, camera poses, and point clouds. Crucially, this 2D-to-3D lifting process provides a transparent window into the model's representations: the resulting 3D reconstructions serve as an intuitive proxy for visualizing and diagnosing the quality of the model's intrinsic spatial knowledge. Extensive experiments across multiple models and benchmarks demonstrate the effectiveness of SpatialSV in enhancing and interpreting MLLMs' spatial intelligence. Furthermore, the framework exhibits strong generalization in semi-supervised settings, validating its potential to leverage unlabeled visual data for scalable, interpretable spatial representation learning.

22.
bioRxiv (Bioinfo) 2026-06-18

Predicting optimal growth temperatures of bacteria using learned structural information from a single protein

Temperature is a fundamental determinant of bacterial physiology and ecology. Optimal growth temperature (OGT) is highly variable across species, contributing to differences in where and when species are most likely to thrive. Although the OGTs for most bacteria remain unknown, the increasing availability of genomes from uncultivated and cultivated taxa has made it advantageous to build genomic, cultivation-independent models to infer OGT. However, pre-existing genomic models often lack the generalizability and mechanistic grounding required for robust inferences of OGT. We propose a novel framework for predicting bacterial OGT which uses learned protein structural signatures of thermal adaptation. We hypothesize that biophysical tradeoffs which dictate enzymatic functions across variable temperatures provide a more robust empirical basis for OGT prediction than broad genomic features. Our OGT-predicting model, ROSEATE, is based on a single gene, adenylate kinase (ADK), that encodes for a ubiquitous enzyme essential for energy homeostasis. ROSEATE uses high-dimensional latent space encoding via MSA Transformer, a protein language model which embeds ADKs in a manner which preserves biophysical information about embedded proteins. We show that the accuracy of the ROSEATE model is on par with other genome-based models, has a high degree of phylogenetic generalizability, and the ESM embeddings effectively capture key temperature-adaptive enzyme characteristics derived from AlphaFold structures. Because ROSEATE is based on analyses of a single ubiquitous protein, it can be used with metagenomic data to infer the community-level variation in bacterial OGTs. We demonstrate this feature of ROSEATE by reconstructing ADK sequences from over 500 environmental and host-associated metagenomes, successfully distinguishing community-wide thermal preferences across diverse habitats, from polar oceans to mammalian guts. By transitioning from genomic proxies to informationally dense protein structural features, this work provides an efficient, interpretable tool for predicting bacterial OGTs across taxa and whole communities.

23.
arXiv (CS.LG) 2026-06-16

Spectral Analysis of Molecular Features: When Richer Features Do Not Guarantee Better Generalization

arXiv:2510.14217v2 Announce Type: replace Abstract: The spectral properties of feature embeddings offer critical insights into model generalization and representation quality. While deep learning models are widely used for molecular property prediction, kernel methods remain competitive in low-data regimes, yet their spectral behavior is largely unexplored. We present the first comprehensive spectral analysis of kernel ridge regression across diverse representations-including molecular fingerprints (ECFP), pretrained transformers, graph neural networks, and 3D descriptors-evaluated on QM9 and 3 MoleculeNet benchmarks. Surprisingly, richer spectral features do not consistently yield better generalization performance, contradicting common representation heuristics used in self-supervised learning (SSL). Across 4 spectral metrics, only ECFP-based kernels show a strictly positive correlation with performance. Transformer and global 3D representations exhibit mixed behavior, whereas local 3D representations show consistently negative correlations. Truncation analysis further emphasizes this disparity: for local 3D representations on thermodynamic targets, fewer than 2\% of eigenvalues (and occasionally as few as 0.02\%) are needed to recover 95\% of performance, whereas ECFP and transformer kernels require significantly more. By demonstrating a strong dependence on both task and representation, our results challenge the heuristic that richer spectra inherently improve generalization, providing new guidance for evaluating representations in SSL and in label-limited scientific tasks.

24.
bioRxiv (Bioinfo) 2026-06-18

Accounting for allelic diversity and multicopy gene detection improves the accuracy of antibiotic resistance genotypic determination

Background Genomic prediction of antimicrobial resistance (AMR) relies on the accurate detection of resistance genes or allelic variants of core genes from raw or assembled genomes sequences. For several bacterial species and antibiotics, AMR genotype-phenotype discrepancies are common, indicating that important sources of error remain unresolved. For Enterococcus faecium, we focused on identifying the sources of discrepancies for tetracycline resistance, for which genotypic detection had shown particularly low accuracy. We investigated the effect of structural variation in antibiotic resistance genes (ARGs), including gene duplications, truncations, interruptions, and mixed configurations of complete and partial gene copies, as a source of genotype-phenotype discrepancies from short-read data. We conduct further extended investigations to other antibiotic families and into another bacterial species: Escherichia coli. Methods We analyzed collections of E. faecium and E. coli genomes, integrating high-quality complete assemblies, simulated Illumina short reads, and matched AMR phenotypic data. The integrity, copy number, and allelic diversity of ARGs were examined for multiple antibiotic classes, and their impact on ARG detection and accuracy of AMR determination was assessed using several commonly used bioinformatic tools (SRST2, ARIBA and AMRFinderPlus). Results For E. faecium, after ruling out the effect of specific tet allelic variants on tetracycline susceptibility, we found that the integrity and copy number of tet(M) had a major effect on detection accuracy. Duplicated and incomplete ARGs are also common in E. faecium genomes, particularly for macrolides (erm(B)) and aminoglycosides (ant(6)-Ia and aph(3')-IIIa). In E. coli, similar patterns were observed for tet(A), erm(B) and aminoglycoside-associated genes (aph(3')-IIIa and ant(6)-Ia). Across ARGs in both species, short-read mapping methods wrongly reported interrupted genes as complete in some instances, while assembly-based methods often failed to resolve complete copies of duplicated genes. Detection accuracy improved when tools were adapted to account for gene integrity and when extended AMR databases incorporating species-specific alleles were included. Conclusions Our findings reveal that bioinformatic limitations in dealing with ARG copy number and completeness, and in accounting for allelic variation, underly a substantial source of genotype-phenotype errors, highlighting the need for improved AMR databases and bioinformatic tools that consider these factors to achieve reliable genomic prediction of AMR.

25.
medRxiv (Medicine) 2026-06-15

SPIRIT-CONSORT-ELM: Element-Level Assessment of Randomized Controlled Trial Reporting Using Large Language Models

Randomized controlled trials (RCTs) play a central role in assessing the benefits and harms of interventions. Incomplete reporting in RCT publications can compromise the verifiability and usefulness of RCTs. SPIRIT and CONSORT reporting guidelines aim to improve the completeness of RCT protocols and results publications, respectively. However, many RCTs are not reported completely. Checking manuscripts automatically could help authors improve the completeness of reports prior to publication. We previously annotated SPIRIT-CONSORT-TM, a corpus of 200 articles (comprising 100 protocol-results publication pairs) using 83 checklist items drawn from SPIRIT 2013 and CONSORT 2010. We also trained machine learning models to automatically assess reporting at the item level. Each checklist item can include multiple constituent elements (i.e., specific details required for that item), and an item might be considered fully reported when all of its elements are present. However, prior work does not explicitly capture or evaluate reporting at the element level. To address this gap, we extended SPIRIT-CONSORT-TM by incorporating element-level annotations and using them to assess reporting completeness (SPIRIT-CONSORT-ELM). We formulated element-level assessment as a machine reading comprehension task, operationalized through 119 questions, where each question targets a specific reporting element within a checklist item. Using the 200 articles included in SPIRIT-CONSORT-TM, two annotators independently answered 119 questions for 50 articles (25 protocol-results pairs) and resolved any discrepancies through discussion; the remaining 150 articles (75 protocol-results pairs) were assessed by a single annotator. We then developed an automated pipeline for element-level assessment using SPIRIT-CONSORT-ELM. The pipeline first applies a PubMedBERT-based model to identify sentences containing item-level reporting information, then it uses a generative large language model (LLM; GPT-5) with chain-of-thought reasoning to answer element-level questions based on the retrieved evidence. Agreement between the two annotators was high (Gwet's AC1: 0.782) and our pipeline achieved high accuracy in identifying element-level reporting evidence (F1: 0.822, Gwet's AC1: 0.796). Ablation studies indicate that chain-of-thought reasoning and the inclusion of illustrative in-context examples modestly improve LLM performance on the machine reading comprehension task. SPIRIT-CONSORT-ELM provides a benchmark for evaluating reporting guideline completeness at the element level, enabling assessment of RCT transparency beyond the simple presence or absence of checklist items and is publicly available at https://osf.io/kznx4/. The automated pipeline establishes a robust baseline for assessing RCT reporting and demonstrates potential as a practical aid for authors, reviewers, and editors to identify and address gaps in completeness and transparency of RCT reports.