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01.
arXiv (CS.AI) 2026-06-16

Orchestrated Reality: From Role-Play to Living, Playable Game Worlds – LLM-Driven World Simulation as a Parameterized-Action POMDP

arXiv:2606.16014v1 Announce Type: cross Abstract: Many games rely on storytelling combined with systems that track levelling, NPC behaviour, and consequence simulation; bridging tightly-authored narrative with deeply-simulated worlds – most acute in sandbox and open-world settings – has been prohibitively expensive. LLM-driven worlds open a new path: a single harness can coordinate numerical state, narrative voice, storytelling pacing, and rule logic together. Realising this requires the LLM system to sustain a persistent world (who is where, what has just happened, what is currently true), which today's deployed systems do not: the narrative voice asserts state in free prose without any validated representation, so a fully autonomous game engine remains infeasible. We treat this as an architectural choice, not a limitation of language models, and report work in progress on a framework – orchestrated reality – that makes the world a canonical object owned by a singleton orchestration agent analogous to the tabletop-RPG Game Master (GM). We formalise an LLM-driven game world for a human player as a Parameterized-Action POMDP: state is a tree of canonical JSON entities, actions decompose as $a=(k, x_k)$ (a discrete intent kind plus structured JSON parameters), the agent observes only a narrative projection $o=O(s)$ of state, and the transition kernel $F$ is an LLM-driven Plan-Diff-Validate-Apply (PDVA) pipeline that commits schema-validated, content-hashed JSON deltas. We give the formal model, a JSON-state example, a worked single-turn example, and a catalogue of 15 illustrative incidents drawn from a real deployment showing the framework in action. Empirical validation through a planned human player study – together with multi-NPC concurrent agency and deployment as an RL environment – is situated as future work.

02.
PLOS Computational Biology 2026-06-01

Histology-informed spatial domain identification through multi-view graph convolutional networks

作者:

by Huihui Zhang, Jiaxing Chang, Zirong Li, Yue Sun, Pinli Hu, Haoxiu Wang, Hang Yang, Yonglin Ren, Xingtan Zhang, Zehua Chen, Kok Wai Wong, Haojing Shao Identifying spatial domains is crucial in spatial transcriptomics, yet effectively integrating gene expression, spatial location, and histology remains challenging. We present STESH, a Spatial Transcriptomics clustering method that combines Expression, Spatial information and Histology. STESH extracts histological features using a convolutional neural network and generates expression, histology, spatial, and collaborative convolution modules for a multi-view graph convolutional network with a decoder and attention mechanism. We evaluated STESH on multiple tissue types and technology platforms. STESH consistently outperformed ten state-of-the-art methods, achieving superior clustering accuracy with the highest scores in adjusted Rand index, normalized mutual information, and Fowlkes-Mallows index.

03.
arXiv (CS.CV) 2026-06-17

When LLMs Analyze Scars: From Images to Clinically-Meaningful Features

Medical image classification faces a fundamental dilemma: while deep learning models achieve remarkable performance at scale, real-world clinical scenarios often suffer from severe data scarcity due to annotation costs, privacy constraints, and disease rarity. This challenge is particularly pronounced in pathological scar classification, where differentiating keloids from hypertrophic scars requires subtle expert knowledge and labeled images are extremely limited. We propose a novel paradigm that repositions large language models (LLMs) as knowledge-driven feature engineers rather than end-to-end classifiers. We call this framework ScaFE (Scar Feature Engineering). Our key insight is that LLMs encode rich medical knowledge that can be externalized as executable feature extraction code, enabling the transformation of high-dimensional images into low-dimensional, clinically interpretable representations. Specifically, we prompt an LLM with established scar assessment criteria to generate deterministic Python code that extracts features aligned with clinical scoring systems such as the Vancouver Scar Scale. Our approach offers three key advantages: (1) data efficiency, achieving robust performance with limited training samples by decoupling knowledge acquisition from statistical learning; (2) privacy preservation, as raw images are processed locally without exposure to external LLMs; and (3) interpretability, through explicit features grounded in clinical reasoning. Extensive experiments on scar classification demonstrate that our method consistently outperforms end-to-end deep learning baselines or using LLMs as black-box classifiers under limited data conditions, establishing a promising direction for integrating LLMs into data-efficient and clinically transparent medical AI systems.

04.
arXiv (CS.CL) 2026-06-17

Beyond Domains: Reusing Web Skills via Transferable Interaction Patterns

Large language model (LLM) web agents are usually deployed as tool callers: each turn, the model reads a fresh page observation and emits one structured tool action. When every action is a low-level primitive, horizons grow quickly and so do policy-facing LLM completions, dominating latency and cost on benchmarks such as Mind2Web and WebArena. Recent systems therefore wrap repeated interaction fragments as web skills: callable tools built from successful trajectories or induced programs, so one call can replace several primitives. However, prior skill libraries are still triggered mainly by instruction similarity or coarse site metadata, which yields low skill reuse on held-out sites and leaves much of the potential step and token reduction on the table. We present SkillMigrator, an agent that learns reusable web skills and transfers them across sites by matching layout structure rather than specific element references. Each induced skill is stored as a transferable interaction pattern (TIP): the skill paired with a structural sketch of the snapshot at induction time. At test time, SkillMigrator retrieves TIPs by layout similarity and grounds their references on the live page. The rest of the stack is standard: accessibility-snapshot observations with stable references, and fixed tool calling over primitives plus skill invocations. Compared with the state-of-the-art approaches, SkillMigrator reduces the average LLM-action count on successful trajectories by 8-10% across both WebArena and Mind2Web at matched success rate.

05.
bioRxiv (Bioinfo) 2026-06-18

fuzzyfold: a high-performance framework for stochastic RNA folding kinetics

作者:

The analysis of nucleic acid secondary structures is overwhelmingly dominated by methods that analyze the thermodynamic equilibrium distribution and which ignore all dynamic aspects of nucleic acid folding. Yet, there are numerous popular examples of nucleic acid folding that rely on kinetic models, such as RNA riboswitches or DNA strand displacement systems. Here, I am presenting fuzzyfold, a Rust-based software package for nucleic acid secondary structure analysis with an explicit focus on stochastic modeling. The framework introduces three-way and four-way shift moves with a biophysically motivated rate-model parameterization, and it is developed with an emphasis on both model flexibility and performance, e.g. allowing for the generation of single co-transcriptional trajectories for thousand-nucleotide long RNA molecules in just a few minutes. The main strength of the fuzzyfold package, however, is its focus on user and developer interfaces for long-term development. It provides easily installable command-line interfaces, e.g. for aggregating data from multiple parallel trajectories efficiently into an ensemble-level dynamic analysis. For developers, the code-base supports straight-forward substitution of thermodynamic and kinetic free-energy models, and a flexible library interface with Python bindings, enabling integration of individual components into custom computational workflows.

06.
Nature (Science) 2026-06-10

Human migration has surged since 2000 — these maps reveal where people are going

Modelling with artificial-intelligence tools has filled gaps in migration data, revealing detailed global population movements from 1990 to 2023. Modelling with artificial-intelligence tools has filled gaps in migration data, revealing detailed global population movements from 1990 to 2023.

07.
arXiv (CS.LG) 2026-06-15

Optimal Hidden-Target Learning for Online Inventory Optimization on General Convex Sets

arXiv:2606.14679v1 Announce Type: new Abstract: Online inventory optimization (OIO) is online convex optimization with physical memory: inventory carryover makes the feasible action set depend on the past. A natural principle, used in stochastic inventory learning and recently in OIO under a single linear capacity constraint, is to maintain a hidden target chosen by an online learner and implement its projection onto the currently feasible order-up-to set. We prove that this simple principle is optimal for OIO on arbitrary bounded convex capacity sets. With online gradient descent as the base learner, the method improves the best known regret guarantee for OIO on general convex sets from inverse to inverse-square-root dependence on the common-demand probability, and we prove a matching lower bound. The same principle gives the first polylogarithmic regret guarantee for strongly convex losses and the first dynamic regret guarantee adapting to Euclidean path variation on general convex capacity sets. The analysis introduces a norm alignment principle: the right state variable is the distance from the hidden target to the feasible set, measured in the same norm as the projection. Under norm alignment, this distance evolves pathwise as a scalar queue, with target movement as arrival and common demand as service. This reduction to one-dimensional queue control resolves the state dependence and extends the guarantees to general convex capacity sets, beyond the reach of prior productwise approaches. Experiments on synthetic and real-world inventory data corroborate the theory.

08.
arXiv (quant-ph) 2026-06-16

On-Demand Coherent Mapping of Telecom Optical States onto Erbium Hyperfine Spins

arXiv:2606.15009v1 Announce Type: new Abstract: Optical quantum memories operating directly at telecom wavelengths are a key enabling technology for long-distance quantum networks, yet on-demand storage onto long-lived ground-state spins in this spectral region has remained elusive due to the challenge of coherently transferring optical excitations to hyperfine spin states. Here we demonstrate spin-wave storage in $^{167}$Er$^{3+}$:Y$_2$SiO$_5$ at 0.8 K and 1.1 T, establishing the core operational primitive required for on-demand telecom quantum memories. Using classical optical control pulses, we coherently transfer collective optical excitations to erbium hyperfine states with transfer efficiency exceeding 12%, enabling on-demand retrieval. We measure a hyperfine population lifetime of 25 s and demonstrate spin-wave storage for up to 25 $\mu$s. By identifying hyperfine inhomogeneous broadening as the dominant present limitation, our measurements define a clear pathway toward second-scale storage through improved spectral tailoring and dynamical decoupling. The results highlight the application of erbium-based solid-state memories for scalable fiber-compatible quantum repeater architectures.

09.
arXiv (CS.CV) 2026-06-17

FATE: Pillar Encoding and Frequency-Aware Training for Event-Based Object Detection

Event cameras are bio-inspired sensors that asynchronously capture logarithmic intensity changes, offering inherent advantages in high-speed and high-dynamic-range scenarios. However, the sparse and asynchronous nature of event streams poses a fundamental challenge for modern deep learning architectures. To enable compatibility with standard models, most existing approaches partition the accumulation window into fixed temporal sub-bins. While effective for spatial processing, this internal discretization discards fine-grained temporal structure and constrains inference to the low temporal frequencies imposed by training supervision. To address this limitation, we propose FATE, a unified framework built upon a novel Pillar Encoding (PE). While operating over discrete macro-accumulation windows dictated by the target frequency, PE avoids internal temporal sub-binning. It organizes events into spatial pillars and approximates their intra-window evolution via projection onto a continuous-time orthogonal polynomial basis. This formulation yields an L2-optimal representation that retains rich temporal dynamics in a dense pseudo-image, mitigating information loss under sparse event conditions. To fully leverage this representation, we introduce Frequency-Aware Training (FAT), a soft mean-teacher curriculum that generates temporally dense pseudo-labels, effectively bridging the mismatch between low-frequency supervision and high-frequency inference. Extensive experiments demonstrate that FATE generalizes across architectural paradigms and consistently outperforms strong baselines. It enables robust object detection at high temporal resolutions up to 200 Hz, while incurring minimal overhead in parameter count and inference latency

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

Improving Code-Switching ASR with Code-Mixing Guided Synthetic Speech

arXiv:2606.19381v1 Announce Type: cross Abstract: Code-switch (CS) Automatic Speech Recognition (ASR) remains challenging due to limited availability of high quality CS text-speech pairs for training. Although synthetic data augmentation via Text-to-speech (TTS) has been explored, existing CS TTS approaches primarily optimise reconstruction fidelity and do not explicitly enforce language-boundary consistency, thereby limiting their effectiveness for CS ASR augmentation. This paper proposes a code-mixing guided preference-learning framework that steers synthetic speech generation toward improved code-switching fidelity using the Code Mixing Index (CMI). Experiments on the SEAME Mandarin-English conversational corpus demonstrate that the proposed method enhances the utility of synthetic data for ASR fine-tuning. Specifically, when fine-tuning Whisper Large, the proposed approach reduces Mixed Error Rate (MER) from 12.1%/17.8% to 8.9%/14.2% on the DevMAN and DevSGE sets, respectively.

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

TacCoRL: Integrating Tactile Feedback into VLA via Simulation

arXiv:2606.11743v1 Announce Type: cross Abstract: Vision-language-action (VLA) models provide strong visual, language, and action priors for robot manipulation, but visual observations alone often miss the local contact state required for contact-rich tasks. We present TacCoRL, a scalable framework that injects Tactile feedback into VLA policies and improves them through sim-real Co-training and simulation-based reinforcement learning (RL), without requiring large-scale tactile pretraining or extensive real-world contact exploration. The key idea is not only adding touch as an input, but learning how contact readings should modulate action responses in near-failure states that are rare in demonstrations and risky to collect on hardware. We use a real-aligned simulator as a closed-loop training environment for contact interaction. Mixed simulated and real trajectories first warm-start tactile-conditioned actions in the pretrained policy. Reinforcement learning with verifiable task rewards then optimizes the policy using simulated contact rollouts. It reinforces tactile-conditioned actions that lead to task completion, while a supervised objective on real trajectories keeps the refined policy anchored to deployment visual, tactile, and action distributions. The resulting policy transfers directly to the real robot without privileged simulation state or online real-world RL. Across four bimanual contact-rich tasks, the final visuo-tactile policy achieves an average success rate of 72.5%, compared to baseline of 50.0%. Result videos and more details are available at https://tac-corl.github.io/

12.
arXiv (quant-ph) 2026-06-16

Witnessing Spin-Orbital Entanglement using Resonant Inelastic X-Ray Scattering

arXiv:2512.06718v2 Announce Type: replace Abstract: Entanglement plays a central role in quantum technologies, yet its characterization and control in materials remain challenging. Recent developments in spectrum-based entanglement witnesses have enabled new strategies for quantifying many-body entanglement in macroscopic materials. Here, we develop a protocol for detecting spin-orbital entanglement using experiment-accessible resonant inelastic x-ray scattering (RIXS). Central to our approach is the construction of a Hermitian generator from experimentally measurable spectra, which allows us to compute the quantum Fisher information (QFI) available in spin–orbital systems. The resulting QFI provides upper bounds for $k$-producible states and thus serves as a robust witness of spin-orbital entanglement. To account for realistic experimental limitations, we further extend our framework to include relaxed QFI bounds applicable to measurements lacking full polarization resolution.

13.
arXiv (CS.CL) 2026-06-15

Succeeding at Scale: Enterprise Retrieval Benchmark Construction and Index-Preserving Query Adaptation for Multi-Tenant Search

Large-scale multi-tenant retrieval systems generate extensive query logs but lack curated relevance labels for effective domain adaptation, resulting in substantial underutilized "dark data." This challenge is compounded by the high cost of model updates, as jointly fine-tuning query and document encoders requires full corpus re-indexing, which is impractical in multi-tenant settings with thousands of isolated indices. We introduce DevRev-Search, a passage retrieval benchmark for technical customer support built via a fully automated pipeline. Candidate generation uses fusion across diverse sparse and dense retrievers, followed by an LLM-as-a-Judge for consistency filtering and relevance labeling. We further study and systematically evaluate index-preserving query-only adaptation strategies that fine-tune only the query-encoder while keeping the document indices fixed. Experiments on DevRev-Search, SciFact, and FiQA-2018 show that parameter-efficient fine-tuning of the query encoder delivers a remarkable quality-efficiency trade-off, enabling scalable and practical enterprise multi-tenant retrieval.

14.
arXiv (CS.LG) 2026-06-15

Can Machine Learning Forecast Rice Yields in Data-Constrained Settings? Satellite Climate Data, National Crop Statistics, and Lessons from Sierra Leone

arXiv:2606.13959v1 Announce Type: new Abstract: Sierra Leone's agriculture operates with almost no data-driven decision support, and no published machine learning study has examined the country's crop yields. We ask whether rice yield can be forecast from data Sierra Leone currently has. Using 25 years of FAOSTAT production data (2000-2024) for nine major crops, we train XGBoost, Gradient Boosting, and Random Forest under a strict anti-leakage protocol with expanding-window walk-forward evaluation across seven held-out years, benchmarked against naive persistence. No model trained on crop statistics alone outperforms persistence. Augmenting with free satellite climate data (CHIRPS rainfall, NASA POWER temperature) reverses this result: a climate-only XGBoost reduces forecast error by one third (RMSE 284 vs 428 kg/ha), a gain that holds for a linear model and is robust to excluding the anomalous 2018 season. Early-season (May-June) rainfall is the dominant predictor, implying seasonal yield risk is observable months before harvest. No model anticipated the 2018 collapse, whose origins were institutional rather than climatic. We translate the findings into policy recommendations for Sierra Leone's Feed Salone Strategy, with a fully open-source pipeline.

15.
arXiv (CS.AI) 2026-06-12

ARROW: Augmented Replay for RObust World models

arXiv:2603.11395v3 Announce Type: replace-cross Abstract: Continual reinforcement learning challenges agents to acquire new skills while retaining previously learned ones with the goal of improving performance in both past and future tasks. Most existing approaches rely on model-free methods with replay buffers to mitigate catastrophic forgetting; however, these solutions often face significant scalability challenges due to large memory demands. Drawing inspiration from neuroscience, where the brain replays experiences to a predictive World Model rather than directly to the policy, we present ARROW (Augmented Replay for RObust World models), a model-based continual RL algorithm that extends DreamerV3 with a memory-efficient, distribution-matching replay buffer. Unlike standard fixed-size FIFO buffers, ARROW maintains two complementary buffers: a short-term buffer for recent experiences and a long-term buffer that preserves task diversity through intelligent sampling. We evaluate ARROW on two challenging continual RL settings: Tasks without shared structure (Atari), and tasks with shared structure, where knowledge transfer is possible (Procgen CoinRun variants). Compared to model-free and model-based baselines with replay buffers of the same-size, ARROW demonstrates substantially less forgetting on tasks without shared structure, while maintaining comparable forward transfer. Our findings highlight the potential of model-based RL and bio-inspired approaches for continual reinforcement learning, warranting further research.

16.
PLOS Computational Biology 2026-06-03

IsoPepTracker: An interactive web application for peptide-driven isoform analysis

作者:

by Araf Mahmud, Chen Huang Alternative splicing affects 95% of multi-exon genes, generating protein isoforms with distinct functions. While current alternative splicing analyses effectively identify splice events at the RNA level, they provide limited protein-level insight. To address this gap, we developed IsoPepTracker (https://www.isopeptracker.org), a user-friendly web application for analyzing and visualizing differential peptides across canonical and novel isoforms that are theoretically detectable by shotgun mass spectrometry-based proteomics. IsoPepTracker features four modules: Canonical Isoform Analysis, Novel Isoform Discovery, Peptide Sequence Search, and Alternative Splicing Analysis. Each module is tailored for distinct and complementary proteogenomics analyses. Users can input genes, novel cDNA sequences, peptides, or alternative splicing results to pinpoint peptides of interest and identify their associations with target genes or isoforms. We demonstrate the straightforward application of IsoPepTracker in proteogenomics through case studies. IsoPepTracker not only provides informative peptide signatures to understand the protein-level consequences of alternative splicing but also supplies peptide candidates for validation in shotgun proteomics.

17.
arXiv (CS.AI) 2026-06-18

Engagement Intensity as a Learner-Modeling Signal for Adaptive AI Ethics Instruction

arXiv:2606.18548v1 Announce Type: cross Abstract: Adaptive AI ethics instruction in graduate research training benefits from intake measures that reflect differences in prior LLM experience. Prior coursework or workshop attendance is an obvious candidate, but it is not clear whether it is associated with pre-instruction ratings on key AI perception items. We compare three candidate intake features, self-reported usage frequency, self-rated LLM familiarity, and prior AI education, across five baseline perception outcomes in 93 bioscience graduate and postdoctoral trainees enrolled in a required research ethics course. Usage frequency shows Holm-corrected associations with all five outcomes, self-rated familiarity with three, and prior AI education with none. A threshold-like pattern at the lower end of the scale is most visible for training interest and accuracy trust rather than appearing as a uniform gradient across all five outcomes. In a short intake survey, reported LLM use is more consistently associated with these perceptions than prior coursework or workshops, with self-rated familiarity serving as a secondary indicator. These results suggest that simple pre-instruction behavioral signals can inform lightweight intake profiling for adaptive AI ethics education.

18.
arXiv (CS.AI) 2026-06-15

FPGA-Based Neural Network Accelerators for Space Applications: A Survey

arXiv:2504.16173v3 Announce Type: replace-cross Abstract: Space missions are becoming increasingly ambitious, necessitating high-performance onboard spacecraft computing systems. In response, field-programmable gate arrays (FPGAs) have garnered significant interest due to their flexibility, cost-effectiveness, and radiation tolerance potential. Concurrently, neural networks (NNs) are being recognized for their capability to execute space mission tasks such as autonomous operations, sensor data analysis, and data compression. This survey serves as a valuable resource for researchers aiming to implement FPGA-based NN accelerators in space applications. By analyzing existing literature, identifying trends and gaps, and proposing future research directions, this work highlights the potential of these accelerators to enhance onboard computing systems.

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

Context-Aware Multimodal Claim Verification in Spoken Dialogues

Every day, millions absorb claims from podcasts and streams that no fact-checker ever sees. Spoken misinformation is built through conversation, where credibility comes not from facts alone but from how claims are framed, reinforced, or left unchallenged across turns. Yet fact-checking has focused on isolated text, leaving dialogue audio under-studied. We introduce MAD2, a new Multi-turn Audio Dialogues benchmark for spoken claim verification, containing 1,000 two-speaker dialogues with 3,368 check-worthy claims and approximately 10 hours of audio, and propose calibrated multimodal fusion of a context-aware audio encoder and a dialogue-aware text model. Across settings, adding dialogue context improves verification, but the gains depend on scenario type. Using only preceding context often matches offline performance, supporting live-moderation settings, and audio contributes most when transcript-based models are destabilized by additional context. Overall, conversational structure matters more for verification than misinformation framing.

20.
arXiv (quant-ph) 2026-06-15

Resolving the Edge of a Quantum Pyramid

arXiv:2606.14698v1 Announce Type: new Abstract: Standing on the shoulders of giants, we resolve the quantum pyramids conjecture, confirming the globally information-optimal measurement for an ensemble of equiangular equiprobable pure states, as conjectured by Englert and \v{R}eháček (arXiv:0905.0510). We do so by proving the remaining entropy inequalities of Holevo and Utkin (arXiv:2506.06700), which certify optimality for obtuse and flat pyramids. For obtuse pyramids, our key contribution is a rigorous proof that local minimizers of the corresponding entropy inequality cannot have three distinct coordinate values. We show that eliminating this family can be reduced to a neat algebraic reciprocal inequality relating branches of the Lambert $W$ function, which may be of independent interest. For flat pyramids, we prove a tight $\ell^p$ inequality for zero-sum vectors that was recently conjectured, proved analytically in dimension $d=3$, and computationally verified for $d\leq 200$ by Holevo and Utkin (arXiv:2603.24017). We prove this bound for all $d\geq 2$ via a technique in symmetric inequalities known as the equal variables method.

21.
medRxiv (Medicine) 2026-06-15

Data-Driven Stochastic Model for Detecting Patientswith Alzheimer's Disease

Alzheimer s disease (AD) is a critical neurological disorder that causes the brain to shrink and leads to the eventual death of brain cells, adversely affecting a person s ability to function. AD is a fast-growing disease in the United States and was the fifth leading cause of death among Americans 65 years of age or older in 2023. In the United States 6.9 million people aged 65 or older were diagnosed with AD, along with a high rate of undiagnosed patients. Thus, the objective of our study is to develop a real data-driven predictive model to identify a patient with AD based on eight risk factors: Age, Gender, ADAS-Cog13, Entorhinal, Fusiform, Intracranial Volume (ICV), Amyloid-Beta, and Tau Protein, with a high degree of accuracy. The quality of the model was evaluated using well-established and sophisticated statistical measures: the area under the receiver operating characteristic curve, calibration plot, Hosmer-Lemeshow goodness-of-fit test, and K-fold cross-validation. If a patient is given information on the above risk factors, our proposed binary logistic regression model can classify the patient as having AD or not with at least 98% accuracy.

22.
arXiv (CS.LG) 2026-06-15

EqCollide: Equivariant and Collision-Aware Deformable Objects Neural Simulator

arXiv:2506.05797v2 Announce Type: replace Abstract: Simulating collisions of deformable objects is a fundamental yet challenging task due to the complexity of modeling solid mechanics and multi-body interactions. Existing data-driven methods often suffer from lack of equivariance to physical symmetries, inadequate handling of collisions, and limited scalability. Here we introduce \name, the first end-to-end equivariant neural fields simulator for deformable objects and their collisions. We propose an equivariant encoder to map object geometry and velocity into latent control points. A subsequent equivariant Graph Neural Network-based Neural Ordinary Differential Equation models the interactions among control points via collision-aware message passing. To reconstruct velocity fields, we query a neural field conditioned on control point features, enabling continuous and resolution-independent motion predictions. Experimental results on 2D and 3D scenarios show that \name achieves accurate, stable, and scalable simulations across diverse object configurations. It achieves $24.34\%$ to $57.62\%$ lower rollout MSE, even compared with the best-performing baseline model. Furthermore, \name could generalize to more colliding objects and extended temporal horizons, and stay robust to input transformed with group action. Code is available at: https://github.com/AI4Science-WestlakeU/EqCollide

23.
PLOS Computational Biology 2026-06-02

Data-driven model reveals increased stability of CAG-expanded <i>huntingtin</i> RNA due to MID1 binding

作者:

by Yuhong Liu, Annika Reisbitzer, Domagoj Dorešić, Jan Hasenauer, Sybille Krauß, Tatjana Tchumatchenko RNA-binding proteins (RBP) are important regulators of RNA metabolism. In neurodegenerative disorders such as Huntington’s Disease (HD), disrupted RBP-RNA interactions contribute to neuronal dysfunction. One such RBP, Midline 1 (MID1), has been shown to aberrantly associate with mutant huntingtin (Htt) RNA, enhancing its translation, yet the mechanism driving this effect remains unknown. Here, we develop a computational model to understand the role of MID1. Based on previously published data, our model predicts that MID1 increases the stability of the Htt RNA. We experimentally validate this prediction, showing that overexpression of MID1 significantly prolongs the half-life of mutant Htt RNA. Furthermore, we evaluate model refinements, including clustering of MID1-bound RNA, which allow capturing all key observations in the data. Together, we provide a data-driven framework that underlines the importance of RBP-RNA interaction in post-transcriptional regulation. This framework also shows how individual molecular reactions jointly determine RNA stability and protein levels in HD.

24.
bioRxiv (Bioinfo) 2026-06-15

SMS: Symmetric Mediation Statistics for Powerful High-Dimensional Mediation Analysis

Background: Mediation analysis of high-dimensional features, particularly molecular-level omics features, provides important opportunities to uncover biological mechanisms underlying human health and disease. However, two central statistical challenges remain: testing the composite-null hypothesis and maintaining power when the exposure-mediator and mediator-outcome associations differ substantially in statistical significance. Existing methods typically rely on accurate estimation of the proportions of the three null types or on the maximum of the two association p-values, and may not always control the FDR well and may have limited power under imbalanced significance. Methods: We propose SMS, a new statistical framework based on symmetric mediation statistics. By exploiting symmetry, SMS calibrates the composite null distribution as a whole for FDR control. It also allows flexible combinations of the two association p-values, including the maximum, and then enables construction of an omnibus test. Moreover, it permits direct use of effect-size estimates, bypassing the need to compute p-values. Results: SMS controlled the FDR across a wide range of simulation scenarios while achieving a substantial sensitivity gain, often around 20 percentage points, over existing methods including HDMT, DACT, and DEI-B. Applications to a metabolomics dataset and a DNA methylation dataset further corroborated these findings. Notably, SMS discovered five plausible mediators in the metabolomics dataset that were missed by all existing methods considered.

25.
bioRxiv (Bioinfo) 2026-06-23

Systematic benchmarking of zero-shot utility and robustness in single-cell transcriptomic foundation models

Single-cell foundation models (scFMs) have been proposed as reusable representations for transcriptomic analysis, yet their practical utility and robustness when applied without task-specific fine-tuning remain incompletely characterized. Here, we systematically evaluated single-cell transcriptomic representations in zero-shot settings across 20 methods, 6 downstream tasks and 1,607 datasets comprising nearly 21.8 million cells. We characterized model behavior along three complementary dimensions: baseline utility, structural robustness, and dataset-level drivers of performance variability. Our large-scale analysis reveals a decoupling between utility and robustness: methods ranking highly on standard benchmarks often show marked instability under shifts in dataset structure. Furthermore, no single model performs uniformly well across tasks. In several tasks, classical statistical representations based on highly variable genes remain competitive under zero-shot conditions. Together, these results define the practical boundaries of zero-shot use in scFMs and provide a large-scale benchmark and decision framework for representation selection in single-cell genomics.