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01.
arXiv (CS.AI) 2026-06-12

AgentRivet: an automated system for producing Rivet routines from journal publications

arXiv:2606.13535v1 Announce Type: cross Abstract: Particle physics collider experiments provide Rivet routines as part of the analysis preservation strategy for model-independent measurements. Rivet is a C++ toolkit that allow new theoretical models to be compared to the measurements, thus aiding the development and tuning of Monte Carlo event generators as well as searches for physics beyond the Standard Model. However, analysis coverage is known to be incomplete, with only 39% of measurements having documented and publicly available Rivet routines. In this article, we design and implement an automated workflow based on Large Language Models with the goal of providing the missing routines. This multi-step workflow, referred to as AgentRivet, extracts the physics analysis information from published papers and writes the missing Rivet routines, with intermediate code- and physics- reviews as part of an autonomous quality control. We report the results obtained using commercial Large Language Models, provided by OpenAI, Anthropic, and Google, for two recent measurements from the ATLAS and CMS experiments. We find that AgentRivet produces competent Rivet routines with few syntax errors. The physics fidelity of the routines is reasonable and follows the explanations given in the relevant publications. Nevertheless, physics-implementation issues do arise and are investigated using the artefacts produced by AgentRivet. The majority of physics implementation issues arise from subtle-but-ambiguous definitions in the given publication, although some models struggle to implement complex observables even when clear definitions are given.

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

Generative Molecular Design with Steerable and Granular Synthesizability Control

arXiv:2505.08774v2 Announce Type: replace-cross Abstract: Designing molecules that are both property-optimal and readily synthesizable is a central challenge in drug discovery. Existing works that do consider synthesizability can jointly output predicted synthesis routes for generated molecules. However, there has been minimal attention in addressing the ease of synthesis and with flexibility to incorporate desired reaction constraints. On the other hand, virtual screening searches for commercially available compounds, but imposes challenges when scaling to ultra-large (billion-size and beyond) chemical spaces. Here, we propose a generative design framework that unifies synthesis-constrained molecular design and ultra-large-scale virtual screening through steerable and granular synthesizability control. Generated molecules satisfy arbitrary multi-parameter optimization objectives with predicted synthesis routes satisfying mix-and-match constraints: including or avoiding certain reactions, incorporating specific building blocks, and minimizing synthesis route length. In an end-to-end in-house campaign targeting BRD4, we designed molecules synthesizable with specific selected reactions and building blocks, synthesized all six selected compounds, and identified two micromolar binders. We further demonstrate that reaction control enables efficient navigation of ultra-large make-on-demand chemical spaces to identify property-optimal candidates. By applying our framework to Chemspace's Freedom 4.0 make-on-demand space (142 billion molecules), we generated ~320k molecules (0.00023% of the library) on a single consumer-grade GPU (with only 8 GB GPU memory) and identified a micromolar Wee1 binder amongst 60 synthesized candidates. The single unified framework thus enables generating novel synthesizable molecules and retrieving catalogue-ready candidates, offering a flexible solution to mitigating the synthesizability bottleneck.

03.
medRxiv (Medicine) 2026-06-15

Quality Improvement Based Implementation and Evaluation of a Decision Aid for Patients with Nephrolithiasis

Introduction Patients with nephrolithiasis face challenges in making a high-quality, preference sensitive decision. Our prior work established feasibility and patient acceptance of a software-based decision aid (DA). The objectives for this study were to identify implementation strategies for the DA in routine care and determine whether DA implementation enhances decisional quality for patients. Methods New nephrolithiasis patients were recruited from the institution Medical Center from June 2018 to April 2024 to receive a software-based pre-visit DA that measured care preferences and used decision analysis to rank treatments. The RE-AIM framework and Plan-Do-Study-Act (PDSA) cycles were used to improve implementation outcomes. Patients completed survey instruments evaluating decisional conflict, shared decision-making, care satisfaction, and treatment choice following their provider visit. These metrics were compared in the DA cohort (n=81) to those in a usual care cohort (n=78) with Wilcoxon rank-sum and Chi-square (or Fishers exact) tests. Results Implementation data revealed sustained reach and progressive improvement in fidelity. The DA cohort reported higher decisional quality relative to controls (p=0.003) and reported greater support/advice to make a choice (p=0.005). The DA cohort more often discussed options with their doctor (87.5% vs 69.2%, p=0.005) and were more likely to be promoters of their provider (p

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

Beware of Aliases – Signal Preservation is Crucial for Robust Image Restoration

Image restoration networks are usually comprised of an encoder and a decoder, responsible for aggregating image content from noisy, distorted data and to restore clean, undistorted images, respectively. Data aggregation as well as high-resolution image generation both usually come at the risk of involving aliases, i.e.~standard architectures put their ability to reconstruct the model input in jeopardy to reach high PSNR values on validation data. The price to be paid is low model robustness. In this work, we show that simply providing alias-free paths in state-of-the-art reconstruction transformers supports improved model robustness at low costs on the restoration performance. We do so by proposing BOA-Restormer, a transformer-based image restoration model that executes downsampling and upsampling operations partly in the frequency domain to ensure alias-free paths along the entire model while potentially preserving all relevant high-frequency information.

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

When, Where, and How: Adaptive Binning for Tabular Self-Supervised Learning

arXiv:2606.19827v1 Announce Type: cross Abstract: Medical tabular data are ubiquitous in clinical research, but deep learning for tables remains underexplored because reliable labels often require costly expert adjudication, even though structured clinical variables are routinely available in tabular form. Self-supervised learning can leverage these unlabeled tables, and recent binning-based pretexts offer a promising inductive bias, but existing objectives fix a single global quantile discretization and apply feature-agnostic supervision. We propose Adaptive Binning, a training-adaptive discretization pretext for tabular SSL that couples discretization to learning through a feature-wise coarse-to-fine curriculum. Motivated by the spectral bias of neural networks and the principles of curriculum learning, our method progressively refines discretization per feature upon plateau detection and selects representation-aware splits to jointly improve value-space concentration and representation-space coherence. A heterogeneity-aware objective unifies categorical reconstruction with ordinal supervision for numerical features, and experiments on public medical tabular datasets under unified evaluation protocols show consistent gains for linear probing and fine-tuning without dataset-specific discretization tuning. We further introduce a medical tabular SSL benchmark with standardized protocols to support reproducible progress in this underexplored domain. Our code is available at https://github.com/labhai/Adaptive-Binning.

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

Learning When to Sample: Confidence-Aware Selective Sampling for Efficient Chain-of-Thought Reasoning

Large language models (LLMs) can achieve strong reasoning performance through chain-of-thought (CoT) reasoning, yet they often generate unnecessarily long reasoning paths that incur high inference cost. Self-consistency-based approaches push accuracy higher still, but they require sampling and aggregating multiple reasoning trajectories, leading to substantial computational overhead. In this paper, we introduce a confidence-aware selective sampling framework that, at inference time, analyzes a single reasoning trajectory to adaptively determine whether to rely on that trajectory alone or trigger multi-path sampling. The framework uses trajectory-level numeric features and sentence-level linguistic features extracted from reasoning states to guide selective multi-path reasoning. We train it on MedQA and evaluate it in-domain on MedQA and under calibration-only transfer on MathQA, MedMCQA, and MMLU, without further fine-tuning. Experimental results show that the proposed framework maintains comparable performance to full and efficient multi-path reasoning baselines, with accuracy changes of $-0.41 \pm 0.58$ and $-0.31 \pm 0.58$ percentage points, respectively, while reducing token usage by $71.7 \pm 5.0%$ and $36.6 \pm 9.1%$. These findings demonstrate that reasoning trajectories contain rich signals for uncertainty estimation, enabling a simple, transferable mechanism to balance accuracy and efficiency in LLM reasoning.

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

Token-Level LLM Collaboration via FusionRoute

Large language models (LLMs) exhibit strengths across diverse domains. However, achieving strong performance across these domains with a single general-purpose model typically requires scaling to sizes that are prohibitively expensive to train and deploy. On the other hand, while smaller domain-specialized models are much more efficient, they struggle to generalize beyond their training distributions. To address this dilemma, we propose FusionRoute, a robust and effective token-level multi-LLM collaboration framework in which a lightweight router simultaneously (i) selects the most suitable expert at each decoding step and (ii) contributes a complementary logit that refines or corrects the selected expert's next-token distribution via logit addition. Unlike existing token-level collaboration methods that rely solely on fixed expert outputs, we provide a theoretical analysis showing that pure expert-only routing is fundamentally limited: unless strong global coverage assumptions hold, it cannot in general realize the optimal decoding policy. By augmenting expert selection with a trainable complementary generator, FusionRoute expands the effective policy class and enables recovery of optimal value functions under mild conditions. Empirically, across both Llama-3 and Gemma-2 families and diverse benchmarks spanning mathematical reasoning, code generation, and instruction following, FusionRoute outperforms both sequence- and token-level collaboration, model merging, and direct fine-tuning, while remaining competitive with domain experts on their respective tasks.

08.
arXiv (CS.LG) 2026-06-19

A Solver-Free Training Method for Predict-then-Optimize

arXiv:2606.19587v1 Announce Type: cross Abstract: We propose a scalable method for training prediction (machine learning) models in the predict-then-optimize paradigm, where model outputs serve as coefficients for a subsequent linear optimization task. Directly minimizing the empirical decision regret is intractable for linear programming and combinatorial optimization since the decision mapping is piecewise constant, and the gradients are zero almost everywhere. While existing methods address this by smoothing the differentiation process, they suffer from scalability issues, since a computationally expensive solver call is required for every gradient evaluation. To address this, we propose a decision-focused learning pipeline based on a measure transformation principle, which yields a new surrogate loss that is completely optimization-solver-free during training. We establish theoretical guarantees, including Fisher consistency and excess risk bounds. Empirically, our method achieves decision quality competitive with state-of-the-art methods while reducing training time by orders of magnitude.

09.
arXiv (CS.CV) 2026-06-18

SC3-Eval: Evaluating Robot Foundation Models via Self-Consistent Video Generation

Evaluating generalist robot manipulation policies in the real world is expensive, slow, and difficult to scale. Action-conditioned video world models offer a scalable alternative by simulating policy rollouts. Autoregressive rollouts accumulate compounding errors, observations across multiple camera views must remain mutually consistent, and the evaluator must generalize to policies whose behaviors lie outside the training distribution. We address these challenges with SC3-Eval, a self-consistent video generation recipe that adapts a pre-trained video foundation model into an accurate policy evaluator by enforcing three complementary forms of consistency. First, forward-inverse dynamics consistency jointly trains the model to predict frames from actions and to recover actions from frames, anchoring generated rollouts to a physically plausible action manifold and counteracting the drift a forward-only model cannot penalize. Second, cross-view consistency trains the model to inpaint each camera view from the other, keeping the multi-camera observation coherent over long rollouts without any explicit memory mechanism. Third, test-time consistency reuses the inverse dynamics mode at inference as a per-action-chunk uncertainty signal that terminates rollouts whose generated frames drift away from the requested actions. We also demonstrate SC3-Eval rollouts reproduce the failure modes that policies exhibit in real-world rollouts, supporting fine-grained diagnostic comparison rather than aggregate ranking alone. Across seven real-world vision-language-action policies, SC3-Eval attains a closed-loop Pearson correlation of $0.929$ and MMRV of $0.119$, outperforming three strong prior video-model-based baselines, and generalizes to new tasks.

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

Robustness of Similarity-based Positional Encoding Under Rotations: Theoretical Analysis and Experimental Validation

Positional encoding is a fundamental component of Transformer architectures, as it injects information about the spatial or sequential arrangement of inputs. Among recent alternatives to standard absolute and sinusoidal encodings, similarity-based positional encoding (simPE) has emerged as a flexible framework for representing positional structure through pairwise relations. simPE was originally designed for medical imaging applications, where geometric robustness is especially relevant: small rotations naturally arise during image acquisition, induced by imaging instruments, patient positioning, or slight acquisition misalignments. Despite its empirical promise, the theoretical behavior of simPE under geometric perturbations has not been fully characterized. In this paper, we study the robustness of simPE with respect to rotations, combining formal theoretical analysis with experimental validation. We first show that simPE is generally not rotation-invariant. We then prove that, under mild Lipschitz assumptions on the elementary components, simPE is stable under rotational perturbations and derive explicit perturbation bounds in Frobenius norm. We validate these findings experimentally on four controlled datasets–a synthetic Arrow dataset, a synthetic Shapes dataset (four geometric shape categories), a synthetic Digits dataset, and a benchmark image classification dataset (FashionMNIST)–in which training and validation images are kept in a fixed canonical orientation while test images are subjected to increasing rotation angles. Across all datasets, simPE consistently outperforms standard learned positional encoding in terms of accuracy, F1 score, precision, and recall under rotation, particularly in the small-to-moderate angle regime, corroborating the theoretical stability guarantees.

11.
medRxiv (Medicine) 2026-06-24

Repetitive Transcranial Magnetic Stimulation over Primary Somatosensory Cortex for Upper Limb Function in Stroke: An Exploratory Randomized Controlled Trial

Background: Stroke often causes Upper Limb (UL) functional impairments. The Primary Somatosensory Cortex (S1) plays an important role in motor learning. Repetitive Transcranial Magnetic Stimulation (rTMS) over S1 could enhance UL recovery. We aimed to explore its preliminary effects on UL motor activity and function post-stroke. Methods: An exploratory parallel-group randomized controlled trial in people with chronic stroke (>3 months) and moderate hemiparesis was conducted. Participants received 20 sessions of active or sham 5Hz rTMS over affected S1, with Robot-Assisted Therapy and Task-Oriented Training, 5 days/week for 4 weeks. The primary endpoint was UL motor activity (Action Research Arm Test, ARAT). Secondary measures were the UL Fugl-Meyer Assessment (UL-FMA) and sensory outcomes. Results: The baseline-adjusted mean difference (MD) in ARAT was 4.05 points [0.78, 7.33], favoring active stimulation. Secondary measures did not favor active stimulation (UL-FMA: MD = 2.62 [-1.51, 6.76]; sensory outcomes showed no between-group differences). Conclusion: High-frequency rTMS over S1 may enhance UL motor activity (ARAT), but no evidence for motor impairment (UL-FMA) or sensory domains was found. Compensation rather than restoration may underlie this improvement. Stimulation targets should match the intended recovery domain, although larger trials are needed to confirm these preliminary findings.

12.
arXiv (quant-ph) 2026-06-25

How to improve the accuracy of semiclassical and quasiclassical dynamics with and without generalized quantum master equations

arXiv:2603.04563v2 Announce Type: replace-cross Abstract: Semi- and quasi-classical (SC) theories can handle arbitrary interatomic interactions and are thus well-suited to predict quantum dynamics in condensed phases that encode energy and charge transport, spectroscopic responses, and chemical reactivity. However, SC theories can be computationally expensive and inaccurate. When combined with generalized quantum master equations (GQMEs), the resulting SC-GQMEs have been observed to enhance the efficiency and accuracy of SC dynamics. Yet, while the mechanism responsible for improved efficiency is clear, the underlying improved accuracy remains elusive. What is worse, SC-GQMEs can yield unphysical dynamics in challenging parameter regimes – a shortcoming that might be avoided if the mechanism of accuracy improvement were understood. Here, we uncover this mechanism. We leverage short-time analyses to prove that exact, "left-handed" time-derivatives delay the onset of SC inaccuracy, and show that their numerical integration yields dynamics with improved accuracy, even without the GQME. We find, however, that these derivatives are a double-edged sword: while offering greater short-time accuracy, they become unphysical in challenging parameter regimes. Because short-lived memory kernels can leverage short-time accuracy while circumventing long-time instability, we develop a protocol to unambiguously determine the memory kernel cutoff, even in challenging regimes where previous treatments had failed. Our insights into accuracy improvement and kernel cutoff protocol can be expected to apply to complex systems that go beyond simple models.

13.
arXiv (CS.LG) 2026-06-19

Quantum ring all-reduce: communication and privacy advantages for distributed learning

arXiv:2606.20344v1 Announce Type: cross Abstract: Machine learning models have scaled to unprecedented sizes, making training across distributed devices the de facto standard in the field. In this work, we explore how quantum communications can make distributed training both more communication-efficient and information-theoretically private, for both classical and quantum learning models. Ring all-reduce is the foundational communication primitive for large-scale distributed training. We present a quantum version that reduces per-link online communication by a provably optimal factor of two using pre-shared entanglement and superdense coding, without requiring the learning model or gradient computation to change. Beyond bandwidth, the primitive enables privacy guarantees that are information-theoretically impossible for any classical protocol, achieving composable {\epsilon}-secure aggregation, via verified entanglement, at a 2x overhead in GHZ copies. Our hybrid quantum-classical communication architecture yields simultaneous communication and security advantages for large scale distributed training, regardless of whether the learning itself is quantum or classical. Finally, we characterise quantum advantages in gradient conflict detection for server-to-client communication under bandwidth constraints, a setting that arises after ring all-reduce is completed, when full gradient broadcast to external clients is infeasible. Two variants of the problem admit different separations. For margin-based alignment testing (\textsc{GapIP}_{\tau}), the quantum advantage is quadratic in the margin parameter: \widetilde{O}({\tau}^{-1}\log P) qubits versus \widetilde{O}(\min(\{\tau}^{-2},P)) bits. For sign-consistency auditing against a private parameter matching (\textsc{TieAudit}_{\epsilon}), the advantage represents an exponential separation in communication complexity: \Omega(\sqrt{P}) bits whereas O({\epsilon}^{-2}\log P) qubits suffice.

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

Structure-aware Knowledge-guided Heterogeneous Mamba for Zygomaticomaxillary Suture Assessment

The Zygomaticomaxillary Suture is a key circummaxillary structure that connects the zygomatic bone and the maxilla, which serves as a primary site of resistance during maxillary advancement, and its maturation status directly influences the timing and efficacy of orthopedic interventions. However, accurate staging of ZMS maturation remains challenging due to subtle high-frequency transitions in suture lines and the global semantic ambiguity between adjacent stages. To address this, we present the first public ZMS dataset, comprising 3,790 ZMS images covering the entire age range from 4 to 24 years. Based on this dataset, we propose SKMamba, a Structure-aware and Knowledge-guided Mamba-based multi-modal framework for automated ZMS maturation assessment. SKMamba adopts a decoupled dual-path architecture that mimics the hierarchical diagnostic process used by experienced orthodontists. We first introduce an Implicit Edge Extractor (IEE), which leverages structural pre-training to reduce trabecular noise and accentuate sutural boundaries. Complementarily, a Cross-Modal Semantic Alignment (CSA) module is designed to incorporate anatomical descriptions from a large language model (LLM). This module helps align local morphological cues with global semantic descriptions while ensuring that objective morphological evidence remains the primary basis for decisions. Extensive experiments on our ZMS dataset demonstrate that SKMamba achieves state-of-the-art performance compared to existing methods. Code is available at https://github.com/galaxygxq1116/SKMamba.

15.
arXiv (CS.CV) 2026-06-24

Full-resolution MLPs Empower Medical Dense Prediction

Dense prediction is a fundamental requirement for many medical vision tasks such as medical image restoration, registration, and segmentation. The most popular vision model, Convolutional Neural Networks (CNNs), has reached bottlenecks due to the intrinsic locality of convolution operations. Recently, transformers have been widely adopted for dense prediction for their capability to capture long-range visual dependence. However, due to the high computational complexity and large memory consumption of self-attention operations, transformers are usually used at downsampled feature resolutions. Such usage cannot effectively leverage the tissue-level textural information available only at the full image resolution. This textural information is crucial for medical dense prediction as it can differentiate the subtle human anatomy in medical images. In this study, we hypothesize that Multi-layer Perceptrons (MLPs) are superior alternatives to transformers in medical dense prediction where tissue-level details dominate the performance, as MLPs enable long-range dependence at the full image resolution. To validate our hypothesis, we develop a full-resolution hierarchical MLP framework that uses MLPs beginning from the full image resolution. We evaluate this framework with various MLP blocks on a wide range of medical dense prediction tasks including restoration, registration, and segmentation. Extensive experiments on six public well-benchmarked datasets show that, by simply using MLPs at full resolution, our framework outperforms its CNN and transformer counterparts and achieves state-of-the-art performance on various medical dense prediction tasks.

16.
bioRxiv (Bioinfo) 2026-06-15

DAQplugin: Deep Learning based Real-time Model Evaluation Plugin for ChimeraX

Although an increasing number of protein structures are determined by cryogenic electron microscopy (cryo-EM), protein structure modeling frequently suffers from residue misassignments and sequence register shifts, particularly in regions with ambiguous density. Here, we present DAQplugin, a ChimeraX plugin that performs real-time evaluation of protein models against cryo-EM density maps using the deep-learning-based residue-wise model quality (DAQ) score. Unlike existing validation tools that are typically applied after model construction, DAQplugin enables real-time deep-learning-based validation during model building and refinement. To our knowledge, DAQplugin is the first tool that provides real-time deep-learning based validation of protein models for cryo-EM map within an interactive modeling environment. In addition to identifying potential modeling errors, DAQplugin also provides guidance for correcting sequence register shifts by suggesting alternative residue placements along the backbone. The computation in this plugin is designed to run efficiently on general CPUs without requiring GPU hardware. Using DAQplugin, users can perform deep-learning-based validation on standard laptops during interactive model building, model-map fitting, and refinement. DAQplugin is able to facilitate more accurate interpretation of cryo-EM density maps and improve the reliability assessment of protein structure models.

17.
arXiv (CS.AI) 2026-06-19

Emergent Alignment

arXiv:2606.19527v1 Announce Type: new Abstract: Can Large Language Models (LLMs) discern when their own outputs are misaligned with human ethics? And can they self-correct? We endow an LLM with a conscience step that reviews its own reasoning and outputs, and we extend the training loss with an alignment component using Direct Preference Optimization (DPO) to steer the model away from non-ethical outputs. The result is an online technique to align models in a wide range of applications: training, fine-tuning, adversarial prompting, and zero-shot learning. It does not require a weaker or stronger judge, relying instead on a frozen copy of itself. In previous work, the Emergent Misalignment scenario showed a range of emergent unethical behaviors from fine-tuning the model to hack code. Instead, we empirically show how to achieve Emergent Alignment: a single high-level introspective question steers training toward an ethical model under the same code hacking scenario.

18.
arXiv (CS.CL) 2026-06-19

Learning to Prompt: Improving Student Engagement with Adaptive LLM-based High-School Tutoring

LLMs can personalize education, although current static-prompt tutoring systems struggle to adapt to diverse academic disciplines. We develop and test a system with subject-aware prompting, based on 14 pedagogical features (e.g., tutor scaffolding, student understanding) extracted from raw transcripts. We first train a prompt routing model in a simulation environment, and then deploy it for online adaptation with actual high-school students. The simulation benchmark shows the router outperforming two static baselines ($0.694$ vs. $0.647$ and $0.64$, $p

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

Lius: Translation Model Based Instructional Lingustic Using Continual Instruction Tuning In Kupang Malay

Large Language Models (LLMs) offer new potential for translation tasks but often experience performance degradation when handling low-resource languages. To address this limitation, we propose an approach for fine-tuning LLMs on a low-resource language, Kupang Malay. Our approach involves designing a set of instructions by leveraging explicit lexical and semantic features from a bilingual dictionary, and introducing Continual Instruction Tuning (CIT), a training paradigm that enables iterative instruction-based training. Experimental results demonstrate that our model, named Lius, yields notable improvements over standard instruction-tuned models by outperforming 4-6 points, and surpassing both Neural Machine Translation (NMT) and Multilingual LLM models by 10-13 points on several evaluation metrics. These findings highlight the potential of our approach to mitigate the reliance on large-scale parallel data in low-resource language translation.

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

Not all Jensen-Shannon Divergence Estimators are Equal

arXiv:2606.16411v1 Announce Type: new Abstract: The Jensen-Shannon divergence is widely reported as a scalar measure of fidelity for synthetic tabular data. Yet, in practice, it is estimated from finite samples using protocols that are often underspecified. This creates a measurement problem. Although the population divergence is well defined, the empirical value depends on the estimator family, sampling protocol, calibration, dimensionality, and class balance. We show that different protocols can yield non-comparable values: marginal-based estimators ignore dependencies in the joint distribution and can severely underestimate divergence, while classifier-based estimators capture joint structure but exhibit strong estimator dependence. We systematically study this behavior across controlled settings with reference divergences and real-world synthetic tabular benchmarks. Our analysis reveals dependence blindness in marginal estimators, prior-shift bias under class imbalance, and estimator sensitivity in high dimensions. To address prior shift, we derive a closed-form posterior correction for classifier-based Jensen-Shannon estimation. Our results show that empirical Jensen-Shannon divergence values are inherently protocol-dependent, making explicit specification of the estimation procedure necessary for meaningful comparison. We provide practical guidelines and an open-source tool for estimator-aware Jensen-Shannon evaluation.

21.
bioRxiv (Bioinfo) 2026-06-11

Calibrated Uncertainty Quantification for Patient-Level AML Drug Sensitivity Prediction Using Split Conformal Prediction

Accurate prediction of ex vivo drug sensitivity in acute myeloid leukemia (AML) patients from transcriptomic data is a critical challenge for precision oncology. Existing computational approaches have explored uncertainty quantification in cancer drug response prediction primarily using cell line data, while patient-level AML models typically rely on heuristic confidence measures rather than statistically calibrated uncertainty estimates. Here, we present a framework applying split conformal prediction to patient-level AML drug response modeling using the BeatAML 2.0 cohort. We trained Elastic Net and XGBoost regressors on bulk RNA-seq gene expression profiles from 318 AML patients, analyzing 34,764 patient-drug observations across 122 compounds. Baseline models achieved median Pearson R values of 0.291 (Elastic Net) and 0.281 (XGBoost) across 122 drugs. Wrapping these models with split conformal prediction yielded well-calibrated prediction intervals across three confidence levels: empirical coverages of 81.4%, 90.7%, and 95.5% against nominal targets of 80%, 90%, and 95%, respectively. Analysis of prediction interval widths revealed substantial drug-class-specific uncertainty patterns, with HDAC and BCL-2 inhibitors exhibiting markedly higher uncertainty than MDM2 inhibitors, suggesting a potential association between transcriptomic predictability and drug mechanism of action, although several drug classes were represented by only a small number of compounds. Predictive uncertainty was not significantly associated with ELN2017 molecular risk classification (Kruskal-Wallis p=0.395) or NPM1 mutation status (p=0.788). These results demonstrate that statistically valid uncertainty quantification can be achieved for patient-level AML drug response prediction despite substantial biological heterogeneity. to the best of our knowledge, no published study has applied split conformal prediction to patient-level ex vivo drug sensitivity prediction in the BeatAML cohort, providing a principled alternative to heuristic confidence scoring approaches. Keywords: Acute myeloid leukemia (AML); Ex vivo drug sensitivity; Conformal prediction; Uncertainty quantification; Precision oncology; BeatAML; Transcriptomic biomarkers; Machine learning.

22.
bioRxiv (Bioinfo) 2026-06-11

DLDN-Bench: A Benchmark Framework for Deep Learning de Novo Peptide Sequencing in Proteomics

De novo peptide sequencing is an essential approach for analyzing mass spectrometry data because it enables the identification of novel peptides without relying on protein sequence databases. Recent advances in deep learning have substantially improved the performance of de novo sequencing methods, but the rapid emergence of new models has led to heterogeneous evaluation practices and limited comparability. To address this, we introduce DLDN-Bench, a benchmark framework including a set of benchmark datasets derived from human muscle biopsy mass spectrometry data retrieved from PRIDE and annotated through consensus across multiple widely used database search engines. Using these datasets, we systematically benchmark recent deep learning-based de novo sequencing tools alongside traditional approaches. Performance is assessed using established metrics, including precision and coverage relative to a pseudo-ground truth defined by cross-engine agreement. To demonstrate the utility of DLDN-Bench, we benchmark four recent deep learning models and make all results publicly available. This benchmark framework provides a standardized basis for comparing state-of-the-art methods and offers an extensible resource for evaluating future tools in de novo peptide sequencing.

23.
arXiv (math.PR) 2026-06-18

Milstein-type Schemes for Hyperbolic SPDEs

arXiv:2512.19647v4 Announce Type: replace-cross Abstract: This article studies the temporal approximation of hyperbolic semilinear stochastic evolution equations with multiplicative Gaussian noise by Milstein-type schemes. We take the term hyperbolic to mean that the leading operator generates a contractive, not necessarily analytic $C_0$-semigroup. Optimal convergence rates are derived for the pathwise uniform strong error \[ E_h^\infty := \Big(\mathbb{E}\Big[\max_{1\le j \le M}\|U_{t_j}-u_j\|_X^p\Big]\Big)^{1/p} \] on a Hilbert space $X$ for $p\in [2,\infty)$. Here, $U$ is the mild solution and $u_j$ its Milstein approximation at time $t_j=jh$ with step size $h>0$ and final time $T=Mh>0$. For sufficiently regular nonlinearity and noise, we establish strong convergence of order one, with the error satisfying $E_h^\infty\lesssim h\sqrt{\log(T/h)}$ for rational Milstein schemes and $E_h^\infty \lesssim h$ for exponential Milstein schemes. This extends previous results from parabolic to hyperbolic SPDEs and from exponential to rational Milstein schemes. Moreover, root-mean-square error estimates are strengthened to pathwise uniform estimates. Numerical experiments validate the convergence rates for the stochastic Schrödinger equation. Further applications to Maxwell's and transport equations are included.

24.
bioRxiv (Bioinfo) 2026-06-11

AGZArank: Investigating epitope-conditioned antibody binder ranking with structure-derived synthetic supervision

Computational antibody design methods can generate large libraries of candidate binders for a target epitope, but prioritizing which candidates to test experimentally remains a major bottleneck. Existing scoring approaches, including physics-based affinity estimators, structure-prediction-derived confidence measures, and inverse-folding likelihood models, provide useful proxy signals but are not explicitly optimized for early enrichment of binders among many structurally similar candidates. Here we investigate epitope-conditioned antibody binder ranking as a dedicated learning problem and introduce AGZArank, a geometric deep learning framework trained with structure-derived synthetic supervision based on normalized pseudo-energy targets. On a benchmark of 45 experimentally validated antibody-antigen interfaces, AGZArank recovered the true binder within the top ten candidates in 44.4% of cases and showed stronger generalization on post-2021 structures than ProteinMPNN, ESM-IF, and PRODIGY. Ablation experiments indicate that ranking performance depends primarily on training scale and alignment between the optimization objective and retrieval-based evaluation, rather than architectural complexity alone. These results support candidate prioritization as a distinct and tractable problem in computational antibody design.

25.
arXiv (CS.CL) 2026-06-17

Variable-Width Transformers

Scaling model size, specifically depth and width, has driven significant progress in transformer-based language models. However, most architectures maintain a constant width across all layers, allocating a fixed parameter and computation budget evenly despite different layers potentially playing distinct computational roles. In this work, we empirically investigate nonuniform capacity allocation across network depth by proposing a $\times$-shaped >