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01.
arXiv (CS.LG) 2026-06-17

Constrained Diffusion Models with Primal-Dual Inference

arXiv:2606.17192v1 Announce Type: new Abstract: This paper develops constrained diffusion models with primal-dual inference (PDI) to sample from optimal distributions of entropy-regularized optimization problems with average constraints. We formalize constrained sampling in the Lagrangian dual domain, where the optimal distribution takes the form of a Gibbs distribution indexed by the optimal dual variable. Rather than estimating this dual multiplier before sampling and freezing it throughout generation, PDI jointly infers the optimal primal distribution and its parametrizing dual variable. Each reverse diffusion step denoises using the score field associated with the current multiplier and then updates the multiplier through dual ascent using the estimated constraint violation of the denoised samples. To enable this conditional score field, we train a single dual-conditioned score network over the family of Gibbs distributions induced by the dual variables encountered during inference. We prove that the time average of the dual variables generated along the inference trajectory converges to a neighborhood of the dual optimum and bound the effect of residual dual mismatch on the terminal distribution through schedule-dependent stability factors. We evaluate PDI on constrained sampling from a mixture of Gaussians, wireless resource allocation, and portfolio management.

02.
arXiv (CS.LG) 2026-06-24

A Differentially Private Weighted Empirical Risk Minimization Procedure and its Application to Outcome Weighted Learning

arXiv:2307.13127v3 Announce Type: replace-cross Abstract: Data used to train predictive models via empirical risk minimization (ERM) often contain sensitive personal information. While differential privacy (DP) provides mathematically provable bounds to protect such data, previous work has focused almost exclusively on unweighted ERM. We consider weighted ERM (wERM) – an important generalization where individual contributions to the objective function vary. We propose the first DP algorithm for general wERM with formal privacy guarantees and derive both its empirical and population excess risk bounds. Crucially, this general wERM framework provides a pathway for deriving privacy-preserving learning methods for individualized treatment rules, including the popular outcome-weighted learning (OWL) approach. We evaluate DP-wERM applied to OWL in simulated and real data experiments. Our empirical results demonstrate that training OWL models via wERM provides strong DP guarantees while maintaining robust performance, proving the method is practical for sensitive, real-world data.

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

Evaluating Open-Source LLMs for Multi-Label ATT&CK Technique Classification on CTI Reports

arXiv:2606.18166v1 Announce Type: cross Abstract: Classifying Cyber Threat Intelligence (CTI) using MITRE Adversarial Tactics, Techniques, and Common Knowledge (ATT&CK) is essential for proactive defense, but historically required extensive human effort. Pre-Large Language Model (LLM) automation sped up this process, but could not resolve the complex language and multi-step attack patterns found in unstructured CTI reports. LLMs addressed previous limitations by using contextual reasoning to understand unstructured text. However, current evaluations rely on simplified, single-technique sentences that ignore the complexity of real-world CTI reports, which often leads to inflated performance results. Consequently, the baseline performance of open-source LLMs on complex unstructured CTI reports remains unevaluated. To address this gap, we constructed a ground-truth dataset of 2,076 human-annotated sentences (1,281 technique-positive, 795 negative) from 83 complex unstructured CTI reports. These sentences were mapped to 114 unique ATT&CK techniques using a six-phase annotation process, achieving \k{appa} = 0.68 inter-annotator agreement. Using this dataset, we evaluated seven open-source LLMs ranging from 8B to 236B parameters across prompt strategy and temperature configurations. The highest-performing LLM achieved a micro-averaged F1 score of 0.22, establishing the empirical baseline for multi-label ATT&CK classification on complex unstructured CTI. Parameter size showed a statistically significant positive correlation with F1 score. Prompt strategy and temperature produced no statistically significant gains across model configurations. These results indicate that current open-source LLMs are insufficient for production-grade ATT&CK classification. The dataset, benchmark, and findings provide a reproducible foundation for future CTI research.

04.
arXiv (CS.AI) 2026-06-12

The Query Channel: Information-Theoretic Limits of Masking-Based Explanations

arXiv:2604.16689v2 Announce Type: replace Abstract: Masking-based post-hoc explanation methods, such as KernelSHAP and LIME, estimate local feature importance by querying a black-box model under randomized perturbations. This paper formulates this procedure as communication over a query channel, where the latent explanation acts as a message and each masked evaluation is a channel use. Within this framework, the complexity of the explanation is captured by the entropy of the hypothesis class, while the query interface supplies information at a rate determined by an identification capacity per query. We derive a strong converse showing that, if the explanation rate exceeds this capacity, the probability of exact recovery necessarily converges to one in error for any sequence of explainers and decoders. We also prove an achievability result establishing that a sparse maximum-likelihood decoder attains reliable recovery when the rate lies below capacity. A Monte Carlo estimator of mutual information yields a non-asymptotic query benchmark that we use to compare optimal decoding with Lasso- and OLS-based procedures that mirror LIME and KernelSHAP. Experiments reveal a range of query budgets where information theory permits reliable explanations but standard convex surrogates still fail. Finally, we interpret super-pixel resolution and tokenization for neural language models as a source-coding choice that sets the entropy of the explanation and show how Gaussian noise and nonlinear curvature degrade the query channel, induce waterfall and error-floor behavior, and render high-resolution explanations unattainable.

05.
arXiv (CS.AI) 2026-06-24

An Introduction to Causal Reinforcement Learning

arXiv:2606.24160v1 Announce Type: new Abstract: Causal inference provides a set of principles and tools that allow one to combine data and knowledge about an environment to reason with questions of counterfactual nature, i.e., what would have happened had reality been different, even when no data of this unrealized reality is currently available. Reinforcement learning provides methods to learn a policy that optimizes a specific measure (e.g., reward, regret) when the agent is deployed in an environment and pursues an exploratory, trial-and-error approach. These two disciplines have evolved independently and with virtually no interaction between them. We note that they operate over different aspects of the same building block, counterfactual relations, which makes them umbilically connected. Based on these observations, novel learning opportunities arise when this connection is explicitly acknowledged and mathematized. To realize this potential, we note that any environment where the RL agent is deployed can be decomposed as a collection of autonomous mechanisms with different causal invariances, parsimoniously modeled as a structural causal model; any standard RL setting implicitly encodes such a model. This formalization allows us to put under a unifying treatment different modes of learning, including online, off-policy, and causal calculus learning, which appear unrelated in the literature. However, these modalities are not exhaustive: we introduce several natural and pervasive classes of learning settings that entail novel dimensions of analysis. Specifically, we introduce and discuss through causal lenses generalized policy learning, where to intervene, imitation learning, and counterfactual learning. These tasks lead to a broader view of counterfactual learning and suggest great potential for studying causal inference and reinforcement learning side by side, which we call causal reinforcement learning (CRL).

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

Quantum Error Correction Codes for Truncated SU(2) Lattice Gauge Theories

Authors:

arXiv:2511.13721v2 Announce Type: replace Abstract: We construct two quantum error correction codes for pure SU(2) lattice gauge theory in the electric basis truncated at the electric flux $j_max=1/2$, which are applicable on quasi-1D plaquette chains, 2D honeycomb and 3D triamond and hyperhoneycomb lattices. The first code converts Gauss's law at each vertex into a stabilizer while the second only uses half of the vertices and is locally the carbon code. Both codes are able to correct single-qubit errors. The electric and magnetic terms in the SU(2) Hamiltonian are expressed in terms of logical gates in both codes. The logical-gate Hamiltonian in the first code exactly matches the spin Hamiltonian for gauge singlet states found in previous work.

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

Distributional Biases in Post-Training: A Markovian Analysis of Reasoning Trajectories

arXiv:2511.07368v3 Announce Type: replace-cross Abstract: Foundation models exhibit broad knowledge but limited task-specific reasoning, motivating post-training strategies such as RL with verifiable rewards (RLVR) and test-time scaling (TTS). While recent work highlights the role of exploration in improving pass@K, empirical evidence points to a paradox: RLVR and ORM/PRM typically reinforce existing paths rather than expanding the reasoning scope, raising the question of why exploration helps if no new patterns emerge. To reconcile this paradox, we adopt the perspective of Kim et al. (2025), viewing easy (e.g., simplifying a fraction) versus hard (e.g., discovering the some symmetry) reasoning steps as low versus high probability Markov transitions. In this tractable model, pretraining corresponds to tree-graph discovering, while post-training corresponds to CoT reweighting. We provably show that, both RLVR and ORM/PRM would favor heavily to several high-probability paths, and thereby forget rare-but-crucial CoTs. Building on this, we further prove that exploration strategies such as rejecting easy instances and KL regularization help preserve rare CoTs. Empirical simulations corroborate our theoretical results.

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

Large Language Models Do Not Always Need Readable Language

Large language models (LLMs) are commonly prompted and interfaced with human-readable natural language, even when the intended reader is another model. This paper investigates whether semantic information can be encoded in compact, non-standard textual forms that sacrifice human readability while remaining recoverable by LLMs. We refer to this class of model-centric textual representations as BabelTele, approached here not as a fixed protocol but as an empirical probe into LLMs' capacity to generate and interpret such representations. Through readability diagnostics, model likelihood measures, human questionnaires, and downstream task evaluations, we find that BabelTele can substantially depart from ordinary natural language while preserving core semantics for instruction-tuned LLMs. As a task-agnostic representational paradigm, BabelTele demonstrates high information density, maintaining 99.5% semantic fidelity even when the text volume is condensed to 27.9% of its original length. We further evaluate its semantic robustness in cross-model transfer, agent memory, and multi-agent communication. Results suggest that BabelTele can reduce context overhead while generally maintaining reliable downstream performance, although its effectiveness depends on the compressor-reader pair and task setting. These findings indicate that human readability, natural-language typicality, and model-side semantic recoverability can be partially decoupled, opening a path toward model-native representations in future exploration of LLM systems.

09.
arXiv (CS.CV) 2026-06-12

Radar-Guided Polynomial Fitting for Metric Depth Estimation

We propose POLAR, a novel radar-guided depth estimation method that introduces polynomial fitting to efficiently transform scaleless depth predictions from pretrained monocular depth estimation (MDE) models into metric depth maps. Unlike existing approaches that rely on complex architectures or expensive sensors, our method is grounded in a fundamental insight: although MDE models often infer reasonable local depth structure within each object or local region, they may misalign these regions relative to one another, making a linear scale and shift (affine) transformation insufficient given three or more of these regions. To address this limitation, we use polynomial coefficients predicted from cheap, ubiquitous radar data to adaptively adjust predictions non-uniformly across depth ranges. In this way, POLAR generalizes beyond affine transformations and is able to correct such misalignments by introducing inflection points. Importantly, our polynomial fitting framework preserves structural consistency through a novel training objective that enforces local monotonicity via first-derivative regularization. POLAR achieves state-of-the-art performance across three datasets, outperforming existing methods by an average of 24.9% in MAE and 33.2% in RMSE, while also achieving state-of-the-art efficiency in terms of latency and computational cost.

10.
bioRxiv (Bioinfo) 2026-06-11

DModE: An end-to-end framework for Differential Modification and Expression Analysis of Nanopore direct RNA sequencing data

Summary: Nanopore direct RNA sequencing (DRS) enables simultaneous quantification of transcript abundance and RNA modifications from native RNA molecules, providing a unique opportunity to study transcriptional and epitranscriptomic regulation within a single experiment. However, comprehensive analysis of DRS data remains challenging, as existing workflows typically focus on individual processing steps and often require manual integration of multiple software packages for expression analysis, modification detection, statistical testing, and visualization. Furthermore, integrated differential expression and differential RNA modification analysis at both gene and isoform resolution remains poorly supported by current workflows. Here, we present DModE (Differential Modification and Expression Analysis), an end-to-end framework for integrated analysis of Nanopore DRS data. DModE combines an Epi2ME-compatible Nextflow preprocessing workflow with a dedicated Python package for downstream statistical analysis, visualization, and reporting. The framework supports differential gene and isoform expression analysis, differential RNA modification analysis at genome and transcript level, metagene profiling, exploratory epitranscriptomic analyses, and integrated assessment of relationships between expression and modification dynamics. Results are automatically summarized in interactive HTML reports, facilitating reproducible and accessible data interpretation. By integrating transcriptomic and epitranscriptomic analyses within a single framework, DModE substantially simplifies comprehensive DRS data analysis and lowers the barrier for studying RNA modification biology using Nanopore sequencing.

11.
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.

12.
bioRxiv (Bioinfo) 2026-06-23

Multi-Scale Machine Learning for Antibody-Antigen Binding Affinity Prediction Using Deep Mutational Scanning and Structural Features

Authors:

Predicting how mutations alter antibody-antigen binding affinity is essential for antibody engineering and vaccine design, yet current methods generalize poorly to unseen complexes. We present a multi-scale machine learning framework integrating 93 descriptors across four modalities: physicochemical, structural, ESM-2 protein language model, and solvent-accessible surface area (SASA)/{Delta}{Delta}G_fold features. Under leave-one-complex-out deep mutational scanning (LOCO-DMS) cross-validation on AbAgym (36,541 mutations, 68 experiments, 13 pathogens), gradient boosting achieved MCC = 0.206; a confidence-stratified ensemble reached MCC = 0.374 (83.5% accuracy, 25.5% coverage). No single modality exceeds the majority baseline alone; only multi-scale fusion succeeds. Boltzmann ceiling analysis shows 45.9% of mutations are near-neutral (|{Delta}{Delta}G| < k_BT), bounding theoretical maximum MCC at 0.473; our method achieves 79.1% of this limit. Five deep learning architectures benchmarked under LOCO-DMS showed self-attention matching gradient boosting (MCC = 0.200). Cross-pathogen transfer failed systematically (mean 46.7%), confirming universal binding predictors remain an open challenge.

13.
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.

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

CoffeeBench: Benchmarking Long-Horizon LLM Agents in Heterogeneous Multi-Agent Economies

arXiv:2606.16613v1 Announce Type: new Abstract: As LLM agents become capable of increasingly long-horizon tasks, evaluating their performance in economic systems is becoming increasingly important. Unlike existing benchmarks that primarily evaluate a single agent interacting with a passive environment, economic systems are inherently multi-agent, requiring autonomous agents to communicate, negotiate, and transact while pursuing their own objectives over extended periods. We introduce CoffeeBench, a benchmark for evaluating LLM agents in a long-horizon multi-agent economy composed of heterogeneous firms. In CoffeeBench, two farmers, two roasters, and two retailers autonomously operate their businesses over a 90-day simulation, each seeking to maximize cumulative net income through communication and transactions while managing cash, inventory, and pricing. The evaluated model controls one coffee roaster, while the remaining firms are controlled by fixed reference agents. Across several recent open-weight and proprietary LLMs, all models outperform a passive baseline that takes no actions, with most achieving positive net income. Analysis of agent behavior reveals substantial differences in long-horizon economic interaction: higher-performing models communicate more actively with other firms, whereas Claude~Haiku~4.5 exhibits an idle-drift failure mode, repeatedly choosing inaction despite producing coherent assessments and plans. We release our code and agent trajectories to support future research.

15.
arXiv (CS.LG) 2026-06-11

Intention Driven Identification of In-Possession Match Phases in Association Football through Temporal Graph Learning

arXiv:2606.09289v2 Announce Type: replace Abstract: Understanding tactical organisation of association football, hereafter referred to as football, requires identifying distinct match phases. Yet in-possession phases are rarely directly observable and are shaped by evolving tactical intentions, rather than spatial patterns alone. This study proposes a data-driven framework for identifying in-possession match phases from spatiotemporal tracking data. Seven German Bundesliga matches recorded at 25 Hz with TRACAB were analysed. A hierarchical phase model was defined with three tactical intentions (Invade Opponent Space, Keep Possession, Scoring) and six phases (Build Up, Progression, Counter Attack, Maintenance, Sustained Threat, Finishing). A Temporal Graph Attention Network (T-GAN) was developed to combine frame-level player-interaction graphs, contextual features, and Transformer-based temporal modelling. Performance was evaluated using frame-level F1 and a sequence-aware Intersection over Truth-Dominance (IoT-D) metric. T-GAN achieved macro-average frame-level F1 scores of 0.87 at the intention level, 0.76 for invasion-related phases, and 0.79 for scoring phases. At the sequence level, mean diagonal IoT-D F1 increased from 0.68 to 0.79 for intentions and from 0.61 to 0.71 for phases after post-processing, indicating improved temporal coherence. Model comparisons showed that sequence modelling was the main driver of segmentation quality, while graph-based relational modelling was particularly beneficial for Counter Attack recognition. Exploratory player attention analysis further suggested that wide and midfield positional groups contributed strongly to phase discrimination. Overall, the framework translates continuous tracking data into tactically interpretable in-possession phase representations, with potential applications in automated match annotation, tactical analysis, and playing-style profiling.

16.
arXiv (CS.CL) 2026-06-24

Reinforcement Learning Towards Broadly and Persistently Beneficial Models

As AI systems are deployed across increasingly diverse and high-stakes settings, model alignment must generalize beyond the tasks and domains seen during training. This is especially important for reinforcement learning (RL), which can introduce unexpected misalignment through reward hacking, deception, or other unintended strategies. We study whether RL on beneficial behavior, instantiated in realistic domains, can produce broad and persistent alignment generalization beyond the training distribution. We construct a dataset of realistic situations designed to measure and train beneficial traits, such as truthfulness, fairness, risk awareness, and corrigibility, spanning varied domains, including health, science, and education. We then train models with RL on this dataset and evaluate them on more than 50 independent benchmarks of alignment and beneficial behavior. Compared to a compute-matched baseline, beneficial trait RL improves performance on over 80% of these out-of-distribution benchmarks. We observe substantial out-of-distribution alignment transfer: a beneficial-behavior RL intervention entirely limited to one domain, health, produces broad improvements on non-health alignment evaluations, including reduced reward hacking, deception, and general misalignment. Finally, we study alignment persistence: whether behavior remains robustly aligned under attempts to steer models towards misalignment. Models trained with beneficial trait RL show improved persistence, including greater resistance to adversarial prompting and harmful finetuning; further work is required to isolate the sources of these effects. These results suggest that RL to reinforce beneficial behavior in realistic domains can produce models that are more robustly aligned with human flourishing.

17.
arXiv (CS.AI) 2026-06-24

When Preferences Fail to Become Incentives: A Utility-Behavior Gap in Large Language Models

arXiv:2606.22974v2 Announce Type: replace Abstract: Recent work on preference elicitation in large language models (LLMs) has demonstrated that, when given a series of choices between two outcomes, LLMs reveal a coherent, model-specific utility structure. Notably, this structure often includes preferences that the models' trainers did not intend, such as valuing people of some nationalities above others, raising the possibility that LLMs might be forming emergent, misaligned goals, which, if true, would have major safety implications. However, the choice paradigms in which these preferences are observed are not reflective of real-world situations in which misaligned behavior would be a practical concern. Therefore, we design an experimental paradigm to probe whether these preferences serve as motivations for LLM behavior in realistic scenarios. First, we reproduce prior findings on consistent preference elicitation. Next, we create a set of common writing tasks - essays, grant proposal abstracts, incident postmortems, and translations - where quality can be assessed by a blind, independent LLM judge panel. Then, we demonstrate that LLMs can be motivated via direct exhortation and other explicit cues to modulate their output quality on these tasks. Finally, we probe whether utilities inferred from explicitly reported preferences can shift output quality on these tasks by offering LLMs high-utility incentives for high-quality outputs. In all tasks, across all models tested, offering LLMs outcomes that they report in the choice paradigm as being highly preferred does not lead them to create higher quality outputs than offering them dispreferred outcomes, or even no outcomes at all. We conclude that the existence of coherent preferences as demonstrated in choice paradigms should not be taken as evidence that those preferences have incentive value for the models or affect their behavior in other contexts.

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

A Qualitative Review of GenAI-Based Methods for Data Generation and Augmentation in Industrial Computer Vision Applications

AI-driven computer vision applications require a profound database to ensure predictable behaviors and performance. Such predictable behaviors are especially important for industrial applications in gaining trust from users. However, such a database is not readily available in industrial applications, and its acquisition is not trivial either. Active learning methods can be applied to ramp up data within a project deployment to iteratively increase the database, and thus the application predictability. Unfortunately, we observe that this often leads to a loss of user trust in the application, which is difficult to regain once lost. This leads to a "chicken-and-egg" dilemma in which neither the database nor the application is developed. In this work, we review state-of-the-art methods and approaches to further boost the database the initial active data ramp-up phase. Here, we focus on recent advancements in GenAI-based data generation and augmentation methods and review their adaptability on an industrial computer vision classification use case. Although we observe a potential for automatic data ramp-up, we also see a domain miss match in between the source (training environment) and target (industrial use-case) - regarding context defined in natural language and object characteristics.

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

Learning task-specific subspaces via interventional post-training of speech foundation models

Speech foundation models, pre-trained on large corpora of unlabelled speech data, produce general-purpose representations which are useful across tasks. However, these representations encode information about salient speech variables in a distributed manner, while downstream speech tasks rely on only some of this variability. In this work, we propose a post-training refinement approach using interventional contrastive learning. By leveraging an interventional dataset and multi-part contrastive loss, we learn a transformation from the entangled representation space of speech foundation models into separate content and speaker subspaces. We evaluate the learnt representations on speaker verification and keyword spotting tasks, showing improved out-of-domain speaker verification performance and evidence that speaker and content information are separated across the learned subspaces.

20.
arXiv (CS.LG) 2026-06-11

Online Learning for Supervisory Switching Control

arXiv:2603.14762v4 Announce Type: replace-cross Abstract: We study supervisory switching control for partially-observed linear dynamical systems. The objective is to identify and deploy a suitable controller for the unknown system by periodically selecting among a collection of $N$ candidate controllers, some of which may destabilize the underlying system. While classical estimator-based supervisory control guarantees asymptotic stability, it lacks quantitative finite-time performance bounds. Conversely, current non-asymptotic methods in both online learning and system identification require restrictive assumptions that are incompatible in a control setting, such as system stability, which preclude testing potentially unstable controllers. To bridge this gap, we propose a novel, non-asymptotic analysis of supervisory control that adapts multi-armed bandit algorithms to a control-theoretic setting. The proposed data-driven algorithm evaluates candidate controllers via scoring criteria that leverage system observability to isolate the effects of state history, enabling both detection of destabilizing controllers and accurate system identification. We present two algorithmic variants with dimension-free, finite-time guarantees, where each identifies the matching controller in $O(N \log^2 N)$ steps, while simultaneously achieving finite $L_2$-gain with respect to system disturbances.

21.
bioRxiv (Bioinfo) 2026-06-16

AutoZyme: An Autonomous Agentic Framework to Optimize Bioinformatics Software

Performance bottlenecks in widely used genomics and bioinformatics software present a substantial and growing burden as biological datasets continue to increase in size and number. Relieving these bottlenecks relies largely on expert manual optimization and therefore remains difficult to scale. Here we present AutoZyme, an agentic framework for scientific software optimization. Given a target function, AutoZyme builds benchmarks, identifies bottlenecks, and iteratively tests code changes, retaining only those that improve runtime while preserving output. We evaluated AutoZyme on 45 functions, improving runtime without substantial memory increases in over 95% of cases considered. Across 38 functions from Seurat, Scanpy and related packages in genomics and bioinformatics, AutoZyme reduced runtime by a median of 8.52-fold, with the largest reductions exceeding 676-fold. The optimized functions are distributed through AutoZyme-Library as drop-in replacements for existing analysis pipelines. We also release AutoZyme as a reusable framework for optimizing additional user-specified packages and functions.

22.
PLOS Computational Biology 2026-06-11

MicroRNA target gene prediction model based on input-feature dependency and sample data expansion technique

Authors:

by Yan Shao, Yazhou Li, Hexin Zhai, Shimin Dong Predicting microRNA target genes is essential for understanding their biological functions. This study developed a miRNA target gene prediction model based on input-feature dependency. Features were treated as multiple random variables, with marginal densities estimated using Gaussian mixture models (GMM) and dependencies captured by regular vine (R-vine) copula to derive joint probability density functions. We constructed class-conditional joint densities for positive and negative samples separately using GMM and R-vine copula, then combined these with prior probabilities using Bayes’ rule to obtain posterior probabilities of positive interactions, using a standard 0.5 probability threshold for deterministic prediction. To address insufficient data and class imbalance, hybrid distribution mega-trend diffusion was used to generate virtual samples for data augmentation. Computational validation showed high predictive performance even when only 30% of the training data were used. As proof-of-concept, we experimentally validated one predicted interaction (miR-8485 targeting JAK2) using dual-luciferase, cellular, and animal experiments, confirming the biological relevance of this specific model-generated prediction. These findings provide a valuable tool for understanding miRNA functions and disease mechanisms.

23.
medRxiv (Medicine) 2026-06-10

Human genetic evidence links serine biosynthesis to diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is a common and disabling condition for which no disease-modifying therapies are available. Glycemic and metabolic drivers do not fully explain why only a subset of individuals with diabetes develop DPN, and genetic contributors remain poorly defined. We aimed to perform a multi-population genome-wide association study (GWAS) of DPN to highlight potential new etiological pathways and therapeutic targets. Methods We performed a multi-population GWAS of neuropathy in people with and without diabetes using the VA Million Veteran Program and UK Biobank, followed by replication in the All of Us Research Program (AoU), and gene-based and gene-set analyses to identify implicated pathways. Causal relationships between circulating serine levels and DPN were further tested using two sample Mendelian randomization. To further evaluate pathogenic potential, we analyzed rare, high impact variants in GWAS implicated genes among individuals with unresolved inherited neuropathies using the GENESIS platform. Findings Among individuals with type 2 diabetes, we identified seven genome wide significant loci (p

24.
arXiv (CS.AI) 2026-06-17

A homotopy-type-theoretic generalization of neurosymbolic inference

arXiv:2606.17851v1 Announce Type: new Abstract: A wide range of neurosymbolic (NeSy) systems compute one functional: a belief-weighted sum of a logical quantity over a space of $\sigma$-structures, of which weighted model counting, fuzzy logic, and probabilistic logic are special cases. This account is built on sets, and a set deliberately forgets two things that are important for NeSy: when two $\sigma$-structures are the same up to a symmetry of the theory, and how many distinct proofs witness a query. Replacing the underlying sets by types, in the sense of homotopy type theory, preserves this information, and turns this functional into a belief-weighted homotopy cardinality, a notion of size that counts each object in inverse proportion to its symmetries. We develop the framework from scratch for NeSy systems, prove a conservativity theorem that recovers the classical functional when symmetries are trivial, and show that the symmetry our framework exposes is exactly the one behind reasoning shortcuts. The payoff is concrete: the shortcut-aware concept posterior that recent methods reach by ensembling or expressive density estimation is the only symmetry-invariant point of the confusion-set simplex, computable in closed form by averaging a single model over the symmetry group. On MNIST reasoning-shortcut benchmarks this single-model wrapper is better calibrated than a diversity-trained ensemble, while leaving label accuracy and identifiable concepts untouched. Code is freely available at https://github.com/bio-ontology-research-group/hott-nesy.

25.
arXiv (CS.LG) 2026-06-19

Low-Energy Reduced RISC-V Instruction Subset Processor for Tsetlin Machine Inference at the Edge

arXiv:2606.19964v1 Announce Type: new Abstract: Tsetlin Machine (TM) is a logic-based machine learning approach that relies on simple bitwise operations and finite-state automata, which makes it attractive for edge AI deployments. Recent work has focused on co-processor and accelerator designs based on Tsetlin Machines (TMs). Although these designs achieve high performance, they typically depend on tightly coupled interfaces, microcode-style programming, and external host processors, limiting flexibility and ease of programming. In this work, we present a domain-specific RISC-V microprocessor architecture and design flow tailored for TM inference. Leveraging the modular structure of RISC-V, we design a reduced instruction subset processor that retains programmability while targeting improved performance and lower energy consumption for TM workloads. Instruction profiling is employed to guide instruction reduction, followed by datapath and control path simplifications tailored to TM inference. Both the baseline RV32IM core and the proposed reduced core are evaluated across multiple datasets and compared with Binarized Neural Networks (BNNs), which serve as a hardware-efficient baseline due to their reliance on bitwise operations during inference. Results show that TM achieves comparable or higher accuracy (e.g., up to 88.18% on CIFAR-2 compared to 60.0% for BNN) while reducing execution time by up to 98% across multiple datasets. Furthermore, the proposed design achieves an average $29.7\times$ reduction in energy consumption, demonstrating its effectiveness for programmable and efficient edge AI systems.