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01.
arXiv (math.PR) 2026-06-16

A Machine-Checked Itô Calculus for Brownian Motion

arXiv:2606.15089v1 Announce Type: cross Abstract: We present a machine-checked development of the $L^2$ Itô calculus of Brownian motion on a bounded time interval $[0,T]$, formalized in Lean 4 on top of Mathlib and the BrownianMotion package. The development contains: the construction of the Itô integral as an isometry of Hilbert spaces, from a predictable-rectangle $\pi$-system through the density of simple adapted processes; the Itô integral as a process, proved to be an $L^2$-continuous martingale through a single structural identity (the integral at time $t$ is the conditional-expectation projection of its terminal value onto $\mathcal{F}t$), from which adaptedness, the martingale property, the contraction bound, and both the terminal and the time-indexed Itô isometries follow as corollaries; and Itô's formula for $C^3$ functions with bounded derivatives, including its time-dependent form $df = f_x,dB + (f_t + \tfrac12 f{xx}),dt$, obtained by a discrete-to-continuous argument through weighted quadratic variation and explicit $L^2$ remainder bounds. To our knowledge this includes the first machine-checked proof of Itô's formula, and the first machine-checked construction of the Itô integral as a martingale-valued process, in any proof assistant. We are deliberate about the boundary: the theory is the $L^2$ theory on $[0,T]$ with bounded-derivative integrand classes; localization to the unrestricted $C^2$ formula, integrators beyond Brownian motion, and pathwise statements are out of scope, and we say precisely why and where. The development is roughly 7,200 lines of Lean across 22 modules; every theorem is sorry-free, the axioms of each headline result are pinned to Mathlib's classical defaults by a build-enforced gate, and the whole is reproducible from a pinned toolchain.

02.
arXiv (CS.CL) 2026-06-12

Multi-Bitwidth Quantization for LLMs Using Additive Codebooks

As large language models (LLMs) are increasingly deployed across heterogeneous hardware with varying resource constraints, the ability to adaptively manage the trade-off between performance and efficiency without retraining is critical. We propose Drop-by-Drop, a novel multi-bitwidth post-training quantization framework that enables inference-time precision control over LLM weights from a single trained model. Our method is theoretically grounded in information theory and successive refinement. We establish that LLM weights, which commonly follow a Gaussian distribution, can be optimally reconstructed with increasing fidelity as additional bits are incorporated, under a weighted mean squared error distortion motivated by LLM loss functions. To realize this in practice, Drop-by-Drop incorporates Matryoshka-style supervision into the loss function, exploiting the structure of additive codebooks. Drop-by-Drop produces a single model where ordered subsets of codebooks yield accurate partial reconstructions at each precision level. This approach significantly reduces storage and memory overhead by allowing a single checkpoint to serve multiple bitwidths, while maintaining competitive perplexity and accuracy across major architectures, such as Qwen, LLaMA, Gemma, and Mistral.

03.
arXiv (CS.AI) 2026-06-15

Crypto x AI, AI x Crypto: A Survey

arXiv:2606.13892v1 Announce Type: cross Abstract: The intersection of crypto x AI is spawning papers, products, online posts, and companies. All the surrounding buzz, though, obscures what exactly has been done, what the opportunities and challenges are, and what open questions deserve attention. This survey paper asks what AI can do for blockchain-based technologies (broadly construed as "crypto") (crypto x AI), and vice versa (AI x crypto). We systematize existing work, summarize key takeaways, highlight open research questions, and offer a perspective on pervasive industry misconceptions, concluding that AI and crypto are still in the very early stages of meaningful integration.

04.
arXiv (CS.AI) 2026-06-19

AAPA: Adversarially Anchored Preference Alignment for Post-Training of Large Language Models

arXiv:2509.25148v2 Announce Type: replace Abstract: Post-training alignment of large language models often combines supervised fine-tuning (SFT) on expert demonstrations with reinforcement learning (RL) from preference or verifiable feedback. SFT provides a useful behavioral anchor but can overfit to static demonstrations, whereas RL encourages exploration but may drift from expert behavior or exploit imperfect rewards. We propose AAPA (Adversarially Anchored Preference Alignment), a plug-in framework that augments existing post-training objectives with a sentence-level adversarial anchoring signal. AAPA compares policy rollouts with offline, pre-collected expert responses using a fixed lightweight discriminator, and therefore requires neither online teacher inference nor discriminator co-training during policy optimization. The same anchoring term can be added to SFT, GRPO, and CHORD while preserving their original training pipelines. Experiments on instruction-following benchmarks show that AAPA consistently improves the corresponding base objectives across model scales. In particular, the staged AAPA configuration improves over a strong GRPO baseline by 5.77\% on \texttt{Qwen3-0.6B} and 3.75\% on \texttt{Qwen3-4B}. Further analyses on response length, log-probability distributions, and discriminator variants suggest that adversarial anchoring provides a stable semantic grounding signal for preference optimization. Code is available at \url{https://github.com/IsFaqq/AAPA}.

05.
arXiv (CS.CV) 2026-06-19

VideoSketcher: Sequential Sketch Generation Using Video Model Priors

Sketching is inherently sequential: strokes are drawn progressively to explore and refine ideas. Yet most generative approaches treat sketches as static images, ignoring the temporal process underlying creative exploration. Modeling this sequential structure remains challenging: prior methods either rely on large-scale human-drawn datasets with limited diversity, or use large language models (LLMs) to produce drawing instructions, often at the cost of visual fidelity. We present VideoSketcher, a method for generating high-quality sketching processes by adapting pretrained text-to-video diffusion models to the sparse, continuous nature of sketch formation. Our key insight is that LLMs and video diffusion models offer complementary strengths: LLMs act as semantic planners that decompose concepts into step-by-step instructions, while video diffusion models serve as powerful "renderers" that translate them into temporally coherent sketch sequences. We introduce a two-stage fine-tuning strategy that decouples temporal structure from visual appearance: stroke ordering is learned from synthetic shape compositions, while style is distilled from as few as seven hand-drawn examples. Despite minimal supervision, our method can generate diverse, high-quality sequential sketches that faithfully follow specified drawing orders. Our framework naturally extends to brush style control and autoregressive generation, supporting artistic applications.

06.
PLOS Computational Biology 2026-06-02

PepAnno: A structure-aware deep learning framework for bioactive peptide prediction, structural visualization, and physicochemical profiling

作者:

by Enyan Liu, Yueming Hu, Liya Liu, Yifan Chen, Shilong Zhang, Sida Li, Haoyu Chao, Luyao Xie, Yi Shen, Liangwei Wu, Julio Raúl Fernández Massó, Ming Chen Peptides are gaining prominence as therapeutic candidates due to their diverse physiological functions and structural simplicity. Although multiple computational tools exist for bioactive peptide prediction, many suffer from limitations such as non-intuitive interfaces, sequence-only representations, insufficient structural awareness, restricted interpretability, or fragmented analysis workflows, leading to reduced research efficiency and higher costs. To address these challenges, we present PepAnno (https://bis.zju.edu.cn/pepanno/), a comprehensive and user-friendly web server for multi-functional peptide annotation. PepAnno is powered by a novel structure-aware, multi-view geometric deep learning framework that integrates pre-trained sequence embeddings with predicted 3D structural graphs through a dual-stream architecture combining a Transformer and a GATv2 network. A cross-modal attention mechanism is employed to effectively fuse semantic and geometric representations, enabling accurate multi-task prediction across 7 key bioactivities, including antimicrobial and anticancer properties. Comprehensive evaluation on seven curated bioactivity datasets demonstrates that PepAnno achieves robust and competitive predictive performance across tasks, consistently outperforming or matching existing methods in terms of discrimination and stability. Beyond functional prediction, PepAnno provides automated calculation of physicochemical properties, structure visualization, and access to an integrated repository of peptide-related databases and tools. By enabling one-click peptide annotation, PepAnno offers an efficient and interpretable solution for large-scale peptide analysis and facilitates downstream experimental design and peptide-based drug discovery.

08.
arXiv (CS.CL) 2026-06-12

BLUEmed: Retrieval-Augmented Multi-Agent Debate for Clinical Error Detection

Terminology substitution errors in clinical notes, where one medical term is replaced by a linguistically valid but clinically different term, pose a persistent challenge for automated error detection in healthcare. We introduce BLUEmed, a multi-agent debate framework augmented with hybrid Retrieval-Augmented Generation (RAG) that combines evidence-grounded reasoning with multi-perspective verification for clinical error detection. BLUEmed decomposes each clinical note into focused sub-queries, retrieves source-partitioned evidence through dense, sparse, and online retrieval, and assigns two domain expert agents distinct knowledge bases to produce independent analyses; when the experts disagree, a structured counter-argumentation round and cross-source adjudication resolve the conflict, followed by a cascading safety layer that filters common false-positive patterns. We evaluate BLUEmed on a clinical terminology substitution detection benchmark under both zero-shot and few-shot prompting with multiple backbone models spanning proprietary and open-source families. Experimental results show that BLUEmed achieves the best accuracy (69.13%), ROC-AUC (74.45%), and PR-AUC (72.44%) under few-shot prompting, outperforming both single-agent RAG and debate-only baselines. Further analyses across six backbone models and two prompting strategies confirm that retrieval augmentation and structured debate are complementary, and that the framework benefits most from models with sufficient instruction-following and clinical language understanding.

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

LegalHalluLens: Typed Hallucination Auditing and Calibrated Multi-Agent Debate for Trustworthy Legal AI

AI systems deployed in legal workflows hallucinate at rates that aggregate metrics report at ~52%, but this average conceals where errors concentrate and in which direction they run, leaving compliance officers without an actionable signal for trustworthy deployment. We present LegalHalluLens, an auditing framework with three components: typed hallucination profiles across four legally-motivated claim categories (numeric, temporal, obligation/entitlement, factual) over CUAD (Hendrycks et al., 2021); a Risk Direction Index (RDI) that reduces omission-versus-invention bias to a single deployment-comparable scalar; and a typed debate pipeline calibrated to both magnitudes and directions. Across 510 contracts and 249,252 clause-level instances we measure a within-model gap of approximately 38-40 pp between obligation/numeric and temporal claims that aggregate reporting hides, and show that two systems with matched 52% rates can carry opposite RDIs. The debate pipeline reduces fabricated detections by 45% with per-category gains tracking the diagnosis, matching commercial APIs with a substantially smaller backbone (4B active parameters). Typed profiles and RDI surface failure modes that aggregate metrics hide; we further show these diagnostics serve as calibration inputs for multi-agent debate pipelines, where Skeptic challenges and asymmetric gates targeted at measured failure modes outperform generically-tuned debate. The framework supports direction-aware procurement, accountability, and agent design for legal AI deployed in the wild.

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

Does the Data Processing Inequality Reflect Practice? On the Utility of Low-Level Tasks

The data processing inequality is an information-theoretic principle stating that the information content of a signal cannot be increased by processing the observations. In particular, it suggests that there is no benefit in enhancing the signal or encoding it before addressing a classification problem. This assertion can be proven to be true for the case of the optimal Bayes classifier. However, in practice, it is common to perform "low-level" tasks before "high-level" downstream tasks despite the overwhelming capabilities of modern deep neural networks. In this paper, we aim to understand when and why low-level processing can be beneficial for classification. We present a comprehensive theoretical study of a binary classification setup, where we consider a classifier that is tightly connected to the optimal Bayes classifier and converges to it as the number of training samples increases. We prove that for any finite number of training samples, there exists a pre-classification processing that improves the classification accuracy. We also explore the effect of class separation, training set size, and class balance on the relative gain from this procedure. We support our theory with an empirical investigation of the theoretical setup. Finally, we conduct an empirical study where we investigate the effect of denoising and encoding on the performance of practical deep classifiers on benchmark datasets. Specifically, we vary the size and class distribution of the training set, and the noise level, and demonstrate trends that are consistent with our theoretical results.

11.
arXiv (CS.CV) 2026-06-16

Physics-Driven Zero-Shot MRI Reconstruction with Non-local Image Priors

Zero-Shot Self-Supervised Learning (ZS-SSL) has emerged as a promising paradigm for accelerated Magnetic Resonance Imaging (MRI) reconstruction, eliminating the reliance on fully-sampled external datasets. However, learning solely from a single under-sampled scan suffers from supervision scarcity and optimization instability, often leading to overfitting or artifacts. To address these challenges, we propose a robust physics-driven ZS-SSL framework that synergizes physical consistency with image-domain non-local priors. Our method introduces three core innovations: (1) a Coil Sensitivity Map (CSM)-Guided Dynamic Repository, which stabilizes the training trajectory by filtering physically inconsistent artifacts based on coil sensitivity constraints; (2) a SPIRiT-based regularization, which enforces k-space self-consistency via a learned correlation kernel and stochastic masking; (3) a Non-Local Self-Similarity (NSS) Pixel Bank, which leverages the high-fidelity reference established by the former modules to explicitly mine non-local anatomical similarities, thereby augmenting supervision in the image domain. Extensive experiments on the FastMRI dataset demonstrate that our approach achieves state-of-the-art performance, particularly under high acceleration factors, effectively bridging the gap between zero-shot learning and supervised methods. The code is available at https://github.com/Zolento/NS-SSL.

12.
PLOS Medicine 2026-06-18

Association between initial benzodiazepine prescribing patterns and time to benzodiazepine discontinuation: A population-based retrospective cohort study

by Nikki Bozinoff, Tanya S. Hauck, Robert A. Kleinman, Matthew E. Sloan, Beth A. Sproule, Simone N. Vigod, Jennifer Wyman, Priscila Pequeno, Tara Gomes Background Long-term benzodiazepine use has been associated with increased risk of morbidity and mortality. Preventing long-term use through safer prescribing practices has received little attention to date. We sought to better understand associations between initial prescription characteristics and duration of benzodiazepine use. Methods and findings This was a retrospective population-based cohort study of 1,820,808 adults in Ontario with incident benzodiazepine prescriptions between January 1, 2013 and December 31, 2020, with follow-up to December 31, 2021. The primary exposure was duration of the index prescription (≤7 days—referent group, 8–14 days, 15–30 days, or >30 days). Secondary exposures were: (a) duration of action of index benzodiazepine(s) prescription (short-acting, long-acting or both); (b) number of benzodiazepine dispensed on index (1 or 2+); and (c) mean daily dose of the index prescription in Diazepam Milligram Equivalents (DMEs). The primary outcome was time to benzodiazepine discontinuation in days. Multivariable models were adjusted for age, sex, anxiety, insomnia, and substance use disorders as well as other important comorbidities and socio-demographic characteristics. The median age at index was 53 years (Interquartile Range (IQR) 38–67), and 62.6% were women. The median time to discontinuation in women was 16 days (IQR: 6–29) while the median time to discontinuation in men was 19 days (IQR: 6–29). Lorazepam was the most commonly prescribed benzodiazepine on index (63.9%), followed by clonazepam (17.3%) and diazepam (5.8%). In multivariable Cox Proportional Hazards Models, longer index prescriptions were associated with a lower likelihood of benzodiazepine discontinuation (adjusted Hazard Ratio (aHR) 0.54 (95% Confidence Interval (CI) [0.54,0.54]) for 8–14 days; aHR 0.26 (95% CI [0.25,0.26] for 15–30 days and aHR 0.14 (95% CI [0.14,0.14]) for >30 days, compared to ≤7 days, respectively). Being prescribed two or more benzodiazepines versus 1 was also associated with a reduced likelihood of discontinuation (aHR 0.59 (95% CI [0.57,0.61])), as was being prescribed long-acting benzodiazepines (aHR 0.80 (95% CI [0.80,0.80])) or a combination of short and long acting benzodiazepine (aHR 0.84 (95% CI [0.80,0.88])) versus short-acting benzodiazepines alone. Mean daily doses of >5 to ≤10 DME and >10 to ≤20 DME were associated with an increased likelihood of discontinuation (aHR 1.03 (95% CI [1.03,1.03]); aHR: 1.03 (95% CI [1.03,1.04])), whereas doses >20 DME were associated with a reduced likelihood of discontinuation (aHR 0.98 (95% CI [0.97,0.98])) compared with ≤5 DME. Findings may be subject to bias from unmeasured confounding. Conclusion This large population-based cohort study found that prescribing shorter courses of benzodiazepines, use of a single benzodiazepine, use of a short-acting agent, were associated with reduced likelihood of long-term benzodiazepine use. Findings suggest that simple changes to prescribing practices could reduce prolonged benzodiazepine use and the morbidity and mortality associated with long-term use of these medications.

13.
arXiv (CS.CL) 2026-06-16

Connecting Speech to Words through Images

How can we learn the mapping between written words and their spoken counterparts in the absence of explicit textual supervision? We present a visually grounded method for building a vocabulary of spoken words using only images and their spoken descriptions. First, image captioning systems are used to build a vocabulary of written words representing salient visual concepts in the images. For each word, we then find utterances whose image captions contain that word. Then we use an unsupervised word discovery technique to align these utterances to locate instances of the target word. The result is spoken word segments that are linked to written words – all accomplished without any text supervision. In spoken word retrieval and keyword spotting experiments, the proposed approach outperforms a strong neural baseline while being more interpretable. These results demonstrate the feasibility of the approach in English and motivate future work on low-resource languages without transcripts.

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

PMOF: A Dataset and Benchmark for Passenger Monitoring Using Overhead Fisheye Cameras

Autonomous staff-free public transport requires reliable in-vehicle passenger monitoring. However, perception inside moving vehicles is challenged by confined spaces, variable illumination, motion-induced background variation, occlusion, and limited viewpoints. To mitigate these spatial constraints, ceiling-mounted fisheye cameras provide full-scene coverage from a single viewpoint. Yet existing public overhead fisheye datasets are recorded in static environments and do not capture the domain shift introduced by vehicle motion. To fill this gap, we introduce PMOF, Passenger Monitoring using Overhead Fisheye cameras, the first public dataset of top-view fisheye imagery captured inside a moving vehicle, comprising over 19k manually annotated frames. PMOF provides rotated bounding boxes, tracking identifiers, and action labels, supporting object detection, tracking, and action recognition. We benchmark PMOF using YOLO26m-obb models fine-tuned under multiple dataset configurations that combine PMOF with existing overhead fisheye datasets. Cross-domain fine-tuning with custom rotation-aware augmentation achieves 94.8% AP50 on PMOF and 96.5% AP50 on an unseen overhead fisheye dataset from a different domain. Our results highlight the domain gap between static and moving environments and show that incorporating PMOF improves detection performance and advances generalization beyond passenger monitoring to broader fisheye-based person detection tasks. The dataset and code are available at https://swermuth.github.io/pmof/.

15.
bioRxiv (Bioinfo) 2026-06-20

The recount3 Python package for programmatic access to uniformly processed RNA-seq data

The recount3 online resource provides tens of thousands of uniformly processed RNA-seq samples across human and mouse from major sequencing repositories like the Sequence Read Archive. While access to these datasets has traditionally been centered in the R/Bioconductor ecosystem, the growing prominence of Python in bioinformatics and machine learning necessitates native, efficient tooling for Python users. Therefore, we present the recount3 Python package with robust application programming interface (API) and command-line interface (CLI) for discovering, downloading, and materializing recount3 resources. The software orchestrates uniform resource locator (URL) resolution, persistent on-disk caching, and the automatic parsing of data into analysis-ready data structures, including Pandas DataFrames and BiocPy RangedSummarizedExperiment objects. The recount3 Python package drastically lowers the barrier to entry for large-scale utilization of RNA-seq data in Python-based computational pipelines, bridging the gap between massive public transcriptomic data and modern machine learning ecosystems.

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

Subsystem Quantum Error Correction for Noisy Quantum Metrology

arXiv:2606.19628v1 Announce Type: new Abstract: Quantum error correction has been successfully applied to enhance the precision of parameter estimation in the presence of noise. Nonetheless, existing methods require a number of noiseless, controllable ancillae and lack efficient encoding and decoding procedures. In this Letter, we demonstrate that subsystem error correction provides a new direction that can substantially simplify the metrological protocol. We derive general conditions under which subsystem stabilizer codes achieve the Heisenberg limit and show that, for broad classes of noise, this can be realized by syndrome-free protocols using at most a single ancilla qubit. Furthermore, we extend this framework to dynamical error correction and show that Floquet codes can protect time-dependent metrological signals in reaching the Heisenberg limit.

17.
arXiv (quant-ph) 2026-06-16

Finite-Dimensional Type I von Neumann Algebras in PyTorch: A GPU-Accelerated Framework for Random Block-Diagonal Operators

arXiv:2606.15882v1 Announce Type: cross Abstract: We present \texttt{torch\_vn\_algebra}, an open-source Python library built on PyTorch for numerical experiments with finite-dimensional Type I von Neumann algebras (direct sums of matrix algebras). The library provides: $\bullet$ a compact batched tensor representation $(B,C,k_{\max},k_{\max})$ that handles both Monte Carlo samples and multiple direct summands; $\bullet$ lazy evaluation of operators to avoid unnecessary memory allocation; $\bullet$ generation of random operators with arbitrary eigenvalue distributions (user-provided samplers) and various unitary ensembles (Haar, $\mathrm{SU}(n)$, COE, CSE, diagonal phases); $\bullet$ functional calculus via SVD (absolute value, square root, inverse, entropy) and a hybrid method for extreme eigenvalues (exact diagonalisation for $k_{\max}\le256$, otherwise power iteration); $\bullet$ three trace functionals (blunt, normalised subspace trace, and the von Neumann tracial state); $\bullet$ GPU-accelerated batched linear algebra for moderate-scale Monte Carlo studies (e.g., $2\times10^4$ samples of $100\times100$ operators). The library is validated against analytical expectations (Haar moments, trace properties). Performance benchmarks on a Tesla P100 GPU are presented and discussed. Limitations and future work are outlined. The code is open-source.

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

Vector Quantized Latent Concepts: A Scalable Alternative to Clustering-Based Concept Discovery

Large language models (LLMs) encode rich semantic information in their hidden states, yet it remains difficult to understand what information these internal representations capture. Latent concepts extracted from hidden states offer a promising direction for interpreting LLMs, but existing clustering-based methods face a trade-off: hierarchical clustering produces coherent concepts but is limited to small datasets due to its quadratic memory cost, while K-Means scales efficiently but may yield less semantically coherent concepts. We propose Vector Quantized Latent Concept (VQLC), a discrete concept learning framework that learns a codebook of latent concepts on frozen hidden states. Across 12 dataset-model settings, VQLC stays close to K-Means in computational cost, scales better than hierarchical clustering, and remains competitive in faithfulness, with the clearest gains on decoder-only models. LLMs-based evaluation, qualitative analysis, and a Sparse Autoencoder (SAE) comparison demonstrate that the learned concepts are interpretable and task-relevant.

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

Single-Stage Hierarchical Rectification for Weakly Supervised Histopathology Segmentation

Existing weakly supervised semantic segmentation (WSSS) methods in computational pathology rely on a multi-stage paradigm: class activation map (CAM) generation, offline pseudo-mask refinement, and fully supervised retraining. While established, this decoupled approach presents fundamental limitations. The multi-stage process not only incurs high computational training costs but also suffers from error propagation: local texture biases in shallow CNN layers generate false-positive artifacts that subsequent refinement steps often fail to correct. To address these persistent challenges through a simple yet highly effective approach, we propose the Single-Stage Hierarchical Rectification (SSHR) framework. Rather than passively refining CAMs post-hoc, our method proactively purifies intermediate feature representations during the forward pass. We introduce a Hierarchical Feature Rectification Module (HFRM) that utilizes deep global semantic context to filter out local anomalies in shallow layers. This mechanism generates high-fidelity activation maps directly within a single training loop. Experiments on the LUAD-HistoSeg and BCSS datasets demonstrate that SSHR outperforms state-of-the-art multi-stage methods. Furthermore, SSHR reduces training duration by 2 to 5 times. This efficiency minimizes computational overhead and accelerates clinical translation for large-scale histopathology workflows. The code is available at: https://github.com/trongduc-nguyen/SSHR

20.
bioRxiv (Bioinfo) 2026-06-19

Morpho-FM: spatial molecular reconstruction from routine H&E histology using transcriptomic foundation-model priors

Routine haematoxylin and eosin (H&E) histology captures tissue architecture at clinical scale, but lacks a direct molecular readout of the transcriptional programmes that organise tumour epithelium, stroma, vasculature and immune compartments. Spatial transcriptomics provides this context, yet cost, workflow complexity and sparse sampling limit routine use. Most existing histology-to-expression models are trained de novo on small paired cohorts and therefore remain weakly constrained when extrapolating from sparse measurements to dense, tissue-wide molecular maps. Here we introduce Morpho-FM, a weakly supervised framework that predicts spatial gene expression from routine H&E whole-slide images by conditioning a pretrained single-cell transcriptomic foundation-model prior on local histological neighbourhoods. A lightweight morphology-to-transcriptome adapter maps cached whole-slide histology features into a transcriptomic decoder, enabling prediction at measured locations, dense full-section reconstruction, and re-aggregation to the original measurement support. Across harmonized prostate cancer benchmarks, Morpho-FM achieved the strongest overall performance among five representative methods, reaching mean per-gene Pearson correlations of 0.286 in rotating single-slide evaluation and 0.298 in multi-slide held-out validation. The framework reproduced this advantage across kidney cancer sections, achieved a mean correlation of 0.210 across 56 directed single-slide evaluations and retained measurable predictive signal after external transfer to clear-cell renal cell carcinoma sections. Controlled ablation analyses identified pretrained transcriptomic initialization as a reproducible source of performance gain exceeding that attributable to changes in the histology feature backbone. Beyond predictive accuracy benchmarks, Morpho-FM recovered ERBB2-enriched tumour compartments, boundary-associated molecular gradients, and annotation-aligned tissue domains across Xenium and HER2ST breast cancer datasets. Together, these results support transcriptomic foundation-model priors as an effective constraint for morphology-conditioned molecular decoding and demonstrate the potential of Morpho-FM to extend spatial transcriptomic insight across routine pathology sections.

21.
Nature Biotechnology 2026-06-05

Structural motif search across the protein universe with Folddisco

作者:

Detecting similar protein structural motifs in large structure collections is computationally expensive. We developed Folddisco, a fast structural motif search tool that uses an index of position-independent geometric features, including side-chain orientation, combined with a rarity-based scoring system. Folddisco is 20-fold faster in querying and fourfold more storage-efficient than existing methods while improving accuracy. Folddisco is freely available online ( https://folddisco.foldseek.com ), along with a webserver ( https://search.foldseek.com/folddisco ). Folddisco enables protein structural motif search in million scale databases.

22.
arXiv (CS.LG) 2026-06-12

Machine Learning-based Two-Stage Graph Sparsification for the Travelling Salesman Problem

arXiv:2604.20236v2 Announce Type: replace Abstract: High-performance TSP solvers such as Lin-Kernighan-Helsgaun (LKH) search within a candidate graph – a small subset of edges pre-selected for the solver – rather than over the complete graph. The two leading sparsification heuristics, $\alpha$-Nearest and POPMUSIC, each fall short of the density-coverage balance: $\alpha$-Nearest is dense with stable recall, while POPMUSIC is sparser but its recall degrades with scale. Their union closes the recall gap while remaining far below the complete graph in density, leaving room for further reduction. Existing learning-based sparsifiers score edges on the complete graph, an approach that is expensive and largely limited to Euclidean instances. We propose a two-stage method that inverts this logic. Stage~1 takes the union of $\alpha$-Nearest and POPMUSIC, achieving near-perfect recall at ${\sim}6N$ edges. Crucially, the union annotates each edge with its source provenance – whether it was endorsed by $\alpha$-Nearest, POPMUSIC, or both. Stage~2 trains a lightweight classifier on these annotated edges and prunes the lowest-scoring ones. Because dual-source edges are almost always optimal, the learning problem reduces to filtering the single-source subset – a substantially easier task than classifying all $O(N^2)$ edges from scratch. Across four distance types, five spatial distributions, and problem sizes from 50 to 500, the pipeline reduces candidate-graph density by $37$-$47\%$ while retaining ${\geq}99.69\%$ of optimal-tour edges, and matches or exceeds the coverage of recent Euclidean-only neural sparsifiers at lower density at TSP500.

23.
arXiv (CS.CL) 2026-06-15

ScoreGate: Adaptive Chunk Selection for Retrieval-Augmented Generation via Dual-Score Statistical Fusion

Fixed-cardinality retrieval injects a constant top-K chunks into the generator regardless of query complexity, causing over-retrieval for narrow queries and under-retrieval for compositional ones. We describe ScoreGate, a lightweight score-space decision mechanism that controls retrieval cardinality at inference time using two scores already produced by the standard pipeline: bi-encoder similarity s_i and cross-encoder reranker score r_i, with no additional model inference calls required. Its core insight is that cross-encoder affirmation can rescue semantically relevant chunks that bi-encoder retrieval ranks poorly due to vocabulary mismatch – a failure mode unaddressed by fixed-K or single-score thresholding. On MS MARCO (200 dev queries), ScoreGate achieves MRR@10 = 0.401 with 35% fewer retained chunks than Standard Top-K. On an internal benchmark (n=300, Fleiss' kappa=0.87), ScoreGate observed zero false positives (95% CI [96.4%, 100%]) at 97.77-99.34% recall, with 34.8% fewer tokens per query and only 31ms added latency. Results on both MS MARCO and real-world production traffic suggest that adaptive retrieval cardinality can improve retrieval efficiency without degrading retrieval quality.

24.
bioRxiv (Bioinfo) 2026-06-19

Tox21mer, A transformer foundation model for Tox21 high-throughput concentration-response curves data

The U.S. Tox21 collaboration has generated a large reference library of high-throughput concentration-response assays. Here we present Tox21mer, a 43.5-million-parameter transformer that encodes each Tox21 concentration-response curve together with assay metadata into a 768-dimensional representation. Tox21mer was pretrained on ~2.5 million curves from 102 assay protocols and 6,727 compounds using masked-response reconstruction as the primary objective, with low-weight auxiliary supervision on assay outcome and AC50. To evaluate the learned representation, we trained lightweight probes on frozen embeddings from concentration-response curves of held-out compounds. The representation supported a macro-F1 of 0.985 for three-class outcome prediction (agonist, antagonist, inactive), a binary F1 of 0.994 for active/inactive prediction, and an R2 of 0.87 for log10(AC50). The learned embeddings formed coherent groupings by curve-class category. A masked-only pretraining variant retained near-baseline probe performance, indicating that the representation is learned largely from the self-supervised objective rather than from auxiliary labels. Ablation analyses further showed that predictive performance depends mainly on curve-level response-value distributions conditioned on assay context, with limited reliance on detailed within-curve ordering. Tox21mer thus provides a reusable foundation representation for Tox21 concentration-response data that can support extrapolation to untested compounds through integration with chemical features or distillation into chemistry-only student models for large-scale external screening.

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

Design and Scheduling of an AI-based Queueing System

arXiv:2406.06855v3 Announce Type: replace-cross Abstract: To leverage prediction models to make optimal scheduling decisions in service systems, we must understand how predictive errors impact congestion due to externalities on the delay of other jobs. Motivated by applications where prediction models interact with human servers (e.g., content moderation), we consider a large queueing system comprising of many single server queues where the class of a job is estimated using a prediction model. By characterizing the impact of mispredictions on congestion cost in heavy traffic, we design an index-based policy that incorporates the predicted class information in a near-optimal manner. Our theoretical results guide the design of predictive models by providing a simple model selection procedure with downstream queueing performance as a central concern, and offer novel insights on how to design queueing systems with AI-based triage. We illustrate our framework on a content moderation task based on real online comments, where we construct toxicity classifiers by finetuning large language models.