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01.
arXiv (CS.AI) 2026-06-19

A Systematic Evaluation of Black-Box Uncertainty Estimation Methods for Large Language Models

arXiv:2606.19868v1 Announce Type: new Abstract: Although large language models (LLMs) have shown strong capabilities across a wide range of tasks, their outputs often remain unreliable and may contain hallucinations, making uncertainty estimation (UE) essential for building trustworthy LLMs. In practice, many mainstream LLMs are only accessible through restricted APIs, where internal signals such as logits and hidden states are unavailable, making black-box UE especially important. However, existing work on black-box UE for LLMs remains fragmented in methodology and lacks a unified empirical comparison. To address this gap, we present a systematic review of black-box UE methods and organize them into five categories: verbalization-based, sampling-based, explanation-based, multi-agent, and hybrid methods. We further build a unified evaluation framework and benchmark 24 representative methods across 4 models and 4 dataset settings. Our results show that no single method consistently dominates across all settings. Nevertheless, methods that reason over and compare candidates in the answer space are generally effective, and hybrid methods that combine multiple uncertainty signals perform well under most conditions. By releasing the benchmark data and a unified evaluation framework, we aim to facilitate reproducible comparisons and support future research, while our empirical findings provide practical guidance for developing future black-box UE methods for LLMs.

02.
arXiv (CS.AI) 2026-06-11

Multi-Rate Mixture of Experts for Accelerating Liquid Neural Network Training

arXiv:2606.12240v1 Announce Type: cross Abstract: Multivariate time-series data often exhibit complex temporal dependencies, irregular sampling, and heterogeneous dynamics across multiple time scales, making accurate sequence modeling particularly challenging. Traditional recurrent neural networks (RNNs), such as Long Short-Term Memory (LSTM) networks, operate in discrete time and may struggle to effectively capture continuous and irregular temporal behaviors. Liquid Neural Networks (LNNs) address some of these limitations through continuous-time dynamics, but standard LNN architectures typically rely on a single dynamical system, limiting their ability to model heterogeneous temporal patterns. To address these challenges, we propose a Multi-Rate Mixture-of-Experts (MR-MoE) framework built on top of Liquid Neural Networks. In the proposed architecture, multiple LNN-based experts operate at distinct time scales, enabling the model to explicitly separate fast-changing dynamics from slow-evolving temporal trends. A gating network further enables adaptive expert specialization based on input conditions. In addition, we incorporate both feature-level and temporal attention mechanisms to improve robustness, interpretability, and long-range dependency modeling. Feature-level attention suppresses noisy or irrelevant variables, while temporal attention selectively focuses on informative historical states. We evaluate the proposed framework on a complex multivariate time-series prediction task and compare it against strong baselines, including LSTM, monolithic LNN, and standard MoE models. Experimental results demonstrate that the proposed MR-MoE framework consistently achieves improved AUROC and AUPRC performance while maintaining favorable computational efficiency. These results highlight the effectiveness of combining continuous-time dynamics, multi-scale expert decomposition, and adaptive attention mechanisms for time-series modeling.

03.
arXiv (CS.AI) 2026-06-12

Examining the Usage of Generative AI Models in Student Learning Activities for Software Programming

arXiv:2511.13271v2 Announce Type: replace-cross Abstract: The rise of Generative AI (GenAI) tools like ChatGPT has created new opportunities and challenges for computing education. Existing research has primarily focused on GenAI's ability to complete educational tasks and its impact on student performance, often overlooking its effects on knowledge gains. In this study, we investigate how GenAI assistance compares to conventional online resources in supporting knowledge gains across different proficiency levels. We conducted a controlled user experiment with 24 undergraduate students of two different levels of programming experience (beginner, intermediate) to examine how students interact with ChatGPT while solving programming tasks. We analyzed task performance, conceptual understanding, and interaction behaviors. Our findings reveal that generating complete solutions with GenAI significantly improves task performance, especially for beginners, but does not consistently result in knowledge gains. Importantly, usage strategies differ by experience: beginners tend to rely heavily on GenAI toward task completion often without knowledge gain in the process, while intermediates adopt more selective approaches. We find that both over-reliance and minimal use result in weaker knowledge gains overall. Based on our results, we call on students and educators to adopt GenAI as a learning rather than a problem solving tool. Our study highlights the urgent need for guidance when integrating GenAI into programming education to foster deeper understanding.

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

Self-Evolving Multi-Agent Systems via Textual Backpropagation

arXiv:2506.09046v3 Announce Type: replace-cross Abstract: Leveraging multiple Large Language Models (LLMs) has proven effective for addressing complex, high-dimensional tasks, but current approaches often rely on static, manually engineered multi-agent configurations. To overcome these constraints, we present the Agentic Neural Network (ANN), a framework that conceptualizes multi-agent collaboration as a layered neural network architecture. In this design, each agent operates as a node, and each layer forms a cooperative team focused on a specific subtask. Our framework follows a two-phase optimization strategy: (1) Forward Phase - Drawing inspiration from neural network forward passes, tasks are dynamically decomposed into subtasks, and cooperative agent teams with suitable aggregation methods are constructed layer by layer. (2) Backward Phase - Mirroring backpropagation, we refine both global and local collaboration through iterative feedback, allowing agents to self-evolve their roles, prompts, and coordination. This neuro-symbolic approach enables our framework to create new or specialized agent teams post-training, delivering notable gains in accuracy and adaptability. Across seven benchmark datasets, our work surpasses leading multi-agent baselines under the same configurations, showing consistent performance improvements.

05.
bioRxiv (Bioinfo) 2026-06-13

PertDiffBench: Benchmarking Diffusion Models for Single-Cell Perturbation Response Prediction

Diffusion models are increasingly used to predict transcriptional responses to perturbations, but whether they improve on simpler generative and representation-based baselines remains unclear. Existing evaluations often do not separate the effects of model architecture, input representation, biological context and metric choice, making it difficult to determine where diffusion-based methods are useful. Here we introduce PertDiffBench, a standardized benchmark for diffusion-based transcriptomic perturbation prediction across single-cell and bulk RNA-seq datasets. PertDiffBench evaluates diffusion-based models across three complementary evaluation settings: standard prediction in known single-cell contexts and bulk perturbation conditions, generalization to unseen cell types, species, drugs and intermediate time points, and stress tests of feature dimensionality, input representation, noise type and gene ordering. Across these settings, diffusion models did not show a consistent advantage. scGen remained a strong baseline in common prediction tasks, whereas scDiffusion was the most competitive diffusion-based method in several generalization settings. Temporal imputation showed a different pattern, with a simple DDPM operating directly in expression space outperforming more specialized models. Stress tests showed that performance was model dependent and sensitive to feature dimensionality, encoder choice, noise type and gene ordering. Pretrained encoders did not consistently improve performance, with the classical scVI representation slightly exceeding STATE in seen-condition and unseen-cell-type settings. These results indicate that diffusion-model performance in perturbation response prediction depends strongly on task design and representation choice. PertDiffBench provides a practical framework for evaluating these models under biologically varied and stress-tested conditions.

06.
medRxiv (Medicine) 2026-06-15

Instrumental Activities of Daily Living in Older Adults with Epilepsy: A Cross-Sectional and Longitudinal Multicenter Study

Objective: Instrumental activities of daily living (IADLs) represent a critical but understudied measure of day-to-day function in persons with epilepsy(PWE). In the multicenter Brain Aging and Cognition in Epilepsy (BrACE) study of PWE aged greater than or equal to 55 years, we examined the proportion, clinical correlates, epilepsy-related predictors, and longitudinal trajectory of IADL impairment. Methods: IADLs were assessed using the Functional Activities Questionnaire (FAQ; range=0 to 30; higher=more impaired); a FAQ greater than or equal to 2 defines MCI-level impairment, and a FAQ greater than or equal to 5 defines dementia-level functional impairment. Multivariable logistic regression identified predictors of baseline function. Global cognition (Montreal Cognitive Assessment [MoCA]), individual cognitive measures, and quality of life (QOL) were compared between the impaired and unimpaired groups. Linear regression evaluated predictors of longitudinal functional decline. Results: Of 57 participants (mean age=66.6 years; female=52.6%), 38.6% (n=22) had MCI-level functional impairment and 17.5% (n=10) had dementia-level functional impairment. In univariate analyses, worse FAQ scores were associated with lower education, higher area deprivation index, early-onset epilepsy (EOE less than 60 years), antiseizure medication polytherapy, and epilepsy localization. In multivariable analysis, temporal lobe epilepsy (OR=4.46, 95% CI=1.09, 21.83,p=0.047), EOE(OR=7.14, 95% CI=1.16, 59.97, p=0.046), and lower education(OR=0.70,95% CI=0.49, 0.93, p=0.025) remained independently associated with baseline MCI-level functional-impairment. Lower education (OR=0.55,95% CI=0.29, 0.84, p=0.021) was the only factor associated with dementia-level IADL-impairment. IADL-impaired participants demonstrated lower verbal memory scores (adjusted p=0.041) and MoCA scores (adjusted p

07.
arXiv (CS.CV) 2026-06-11

FreqKD: Frequency-Decoupled Cross-Modal Knowledge Distillation for Infrared Object Detection

Transfer learning from large-scale RGB foundation models to infrared (IR) imagery through knowledge distillation (KD) remains challenging due to fundamental differences in image formation physics. We investigate the spectral structure of the RGB–IR modality gap and observe that feature divergence is not uniform across spatial frequencies: low-frequency components (shape, layout) show greater cross-modal alignment than high-frequency components (texture, fine edges), which reflect modality-specific characteristics. Based on this analysis, we propose FreqKD, a frequency-decoupled distillation framework that applies asymmetric supervision adapted to each band's cross-modal consistency. The method employs strict mean squared error (MSE) on the low-frequency band to preserve shared structural information and a relaxed log-MSE loss (weighted at 0.1) on the high-frequency band to provide edge guidance while tolerating texture differences. Spectral divergence analysis on 500 paired samples shows that high-frequency divergence exceeds low-frequency divergence by a factor of 2.4x on average across all analysed transformer layers. On KAIST multispectral pedestrian detection, FreqKD achieves 64.1 mAP50, improving 2.4 points over the DINOv2 baseline. The learned representation transfers across datasets (FLIR ADAS, +2.1 mAP50), tasks (MFNet segmentation, +1.85 mean intersection-over-union), and architectures (ResNet-50, +1.0 mAP50). Code is available at: https://anonymous.4open.science/r/freq_decoupled_kd-5E5A

08.
arXiv (quant-ph) 2026-06-19

Measuring Rényi entropy with an Echo Protocol

arXiv:2504.05237v3 Announce Type: replace Abstract: We present efficient and practical protocols to measure the second Rényi entropy, whose exponential is known as the purity. Our approach is based on expressing the purity in terms of transition probabilities generated by an echo-type forward-backward evolution sequence, making it applicable to quantum many-body systems. Notably, our approach does not rely on random-noise averaging, a feature that can be extended to protocols to measure out-of-time-order correlation functions, as we demonstrate. By way of example, we show that our protocols can be practically implemented in superconducting qubit-based platforms, as well as in cavity-QED trapped ultra-cold gases.

09.
arXiv (quant-ph) 2026-06-15

Quasilinear Equivalence Checking for Detector Error Models

arXiv:2606.14677v1 Announce Type: new Abstract: A Detector Error Model (DEM) is a structured representation of error mechanisms in quantum circuits, which has gained popularity in quantum compilation pipelines for its ability to capture fault-tolerance at a circuit level. It lists error mechanisms as instructions targeting detectors and observables, specifying for each physical fault channel the probability that the fault fires, the detectors it triggers, and the observables it flips. In this paper, we develop an equational theory for DEMs, with its associated categorical semantics. We present a sound, terminating, confluent rewriting system for DEM terms, formulating it as a symmetric monoidal theory (a PROP) over the Giry monad. We prove that every DEM term has a unique normal form, which can be computed efficiently in quasilinear time $O(k|E|\log|E|)$, where $|E|$ is the number of instructions and $k$ bounds the size of a target set. This provides a complete set of invariants (via Tanner graphs) for structural DEM equivalence. We provide the first static decision procedure for DEM equivalence, with rigorous correctness guarantees. It is complete (decides full decoder-equivalence exactly) for non-adaptive quantum error correction (QEC) pipelines, and scales to a sound and applicable decision procedure for partially-adaptive circuits (lattice surgery, distributed QEC, ...) without suffering exponential overhead. We discuss its application to the verification and optimisation of quantum compilers.

10.
arXiv (CS.LG) 2026-06-11

DeepRHP: A Hybrid Variational Autoencoder for Designing Random Heteropolymers as Protein Mimics

arXiv:2606.11651v1 Announce Type: new Abstract: Synthetic random heteropolymers (RHPs), consisting of a predefined set of monomers, offer an approach toward the design of protein-like materials. These RHPs, if designed appropriately, can mimic protein behavior and function. As such, there is a need for computational tools to efficiently guide RHP design. We bridge this gap by developing DeepRHP, a modified variational autoencoder (VAE) model under a semi-supervised framework. By equipping a classical VAE with an additional feature-based VAE, DeepRHP forces the latent space to capture structures of critical chemical features as well as individual RHP sequence patterns. In this sense, our method is versatile by allowing any relevant features to be incorporated in a hybrid manner. We demonstrate the effectiveness of DeepRHP by suggesting potential monomer compositions that stabilize membrane proteins (e.g. Aquaporin Z) in non-native environments and cross-validating our prediction with published results. The concordance between our model and true RHP function suggests strong potential in utilizing hybrid autoencoder architectures to guide RHP design for proteins and other biological compounds.

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

Global Ease of Living Index: a machine learning framework for longitudinal analysis of major economies

arXiv:2502.06866v3 Announce Type: replace-cross Abstract: The drastic changes in the global economy, geopolitical conditions, and disruptions such as the COVID-19 pandemic have impacted the cost of living and quality of life. It is essential to comprehend the long-term implications of the cost of living and quality of life in major economies. A transparent and comprehensive living index must include multiple dimensions of living conditions. In this study, we present an approach to quantifying the quality of life through the Global Ease of Living Index that combines various socio-economic and infrastructural factors into a single composite score. Our index utilises economic indicators that define living standards, which could help in targeted interventions to improve specific areas. We present a machine learning framework to address missing data for certain economic indicators in specific countries. We then curate and update the data and use a dimensionality reduction approach (Principal Component Analysis and Factor Analysis) to create the Ease of Living Index for major economies since 1970. Our work significantly adds to the literature by offering a practical tool for policymakers to identify areas needing improvement, such as healthcare systems, employment opportunities, and public safety. Our approach with open data and code can be easily reproduced and applied to various contexts, providing transparency and accessibility for ongoing research and policy development in quality-of-life assessment.

12.
arXiv (CS.CL) 2026-06-19

Code-Switching Reveals Language Anchoring in Multilingual LLMs

Multilingual Large Language Models (MLLMs) are increasingly expected to handle Code-Switched (CS) inputs, yet mixing languages frequently degrades performance relative to source- or target-language monolingual counterparts. To understand this degradation, we use grammar-forced CS as a controlled diagnostic setting for locating CS representations relative to their source and target counterparts. We introduce Anchor Bias, a geometric measure that quantifies language anchoring, whether a CS hidden state aligns closer to its source or target language counterpart. Across diverse MLLMs, Anchor Bias reveals a consistent grammar-frame effect: source-framed CS stays source-anchored, whereas target-framed CS shifts target-ward and shows larger Question Answering (QA) degradation. Motivated by this representational pattern, we propose CANVAS (Contextual Anchor-based Neural Vector Alignment Steering), an inference-time intervention that extracts a source-side canvas from the input and softly steers target-language hidden states toward the source anchor during prefill. CANVAS consistently recovers QA F1 across MLLMs and CS conditions, showing that internal anchoring signals provide an actionable target for mitigating CS inference failures.

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

Comparing Human Gaze and Vision-Language Model Attention in Safety-Relevant Environments

Human visual attention plays an important role in how people perceive and respond to environments containing potential risks. This study investigates whether large vision-language models can identify the same regions of a scene that attract human attention in safety-relevant environments. Eye-tracking data were collected from ten participants viewing 33 scene images representing environments with varying levels of potential risk using Pupil Invisible wearable glasses. Gaze coordinates were mapped onto stimulus images to generate population-averaged human gaze heatmaps. In parallel, GPT-4o was prompted through the OpenAI Vision Application Programming Interface (API) to generate spatial predictions of visual attention, which were converted into saliency maps for comparison with human gaze patterns. Spatial alignment between human gaze heatmaps and model-generated saliency maps was evaluated using four complementary metrics: Pearson correlation (r = 0.515 +- 0.117), Normalised Scanpath Saliency (NSS = 0.988 +- 0.323), Kullback-Leibler divergence (KL = 1.766 +- 0.844), and Area Under the Receiver Operating Characteristic Curve using the Judd formulation (AUC-Judd = 0.806 +- 0.076). A cross-model comparison with Gemini Pro, Gemini Flash, and Claude showed that all models exceeded the AUC-Judd chance baseline of 0.5 and achieved positive NSS scores. Gemini Pro demonstrated the strongest spatial localisation according to three of the four metrics, whereas GPT-4o produced the closest distributional match to human attention as measured by KL divergence. These findings suggest that large vision-language models can identify regions that broadly correspond to where humans direct visual attention in safety-relevant scenes without requiring eye-tracking training data. The results highlight the potential of vision-language models as a scalable tool for approximating human attentional patterns.

14.
arXiv (CS.AI) 2026-06-12

(Human) Attention Is (Still) All You Need: Human oversight makes AI-assisted social science reliable

arXiv:2606.12848v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly used for tasks once reserved for trained researchers, including hypothesis generation, specification choice, and drafting conclusions. We argue that the reliability of AI-assisted research depends not only on model capability, but also on how cognitive labour is structured between humans and machines. We study this problem through Human-in-the-Loop Economic Research (HLER), a decision architecture based on pre-commitment, decision sequencing, accountability, and attention allocation. In a pre-specified 2*4 factorial experiment with 280 complete research runs across four datasets, an unconstrained multi-agent baseline produced critical failures in 72% of runs. Using the same underlying model, the same agent decomposition, and identical prompts for the shared reasoning agents, HLER reduced the failure rate to 16% by imposing three architectural commitments: LLMs reason but do not execute data work, data and estimation are handled deterministically, and three human decision gates bind the workflow. Fisher's exact test rejects equality of failure rates at p

15.
PLOS Computational Biology 2026-06-11

A zero-parameter first-principles gate framework for full-length TP53 missense variant interpretation

by Masamichi Iizumi Missense variant interpretation often achieves useful predictive performance but remains mechanistically opaque, particularly in proteins that combine structured domains with intrinsically disordered regions (IDRs). We developed Gate & Channel, a zero-parameter, first-principles framework for full-length TP53 missense variant analysis in which each prediction is generated by explicit IF-THEN gates derived from physicochemistry, geometry, structural constraints, and polymer physics rather than fitted weights. Variants are evaluated across independent channels representing distinct physical failure modes; a variant is predicted disruptive if any gate closes. A second hierarchical layer (“Geta”) encodes physically grounded post-closure exceptions, allowing sensitivity and specificity to be improved on disjoint variant populations. The v18 framework consists of 12 channels and 2 Getas spanning structured domains and IDRs, capturing DNA-contact disruption, Zn coordination, burial-dependent packing, secondary-structure compatibility, post-translational modification chemistry, short linear motif disruption (including a multi-partner coupled-folding face), proline-directed kinase recognition, and IDR-specific proline and glycine backbone constraints. Across 1,369 TP53 missense variants, the framework achieved 84.5% sensitivity and 89.1% positive predictive value, with 90.9% sensitivity preserved in the DNA-binding core and all 9/9 hotspot mutations captured. A post hoc audit of discordant IDR calls indicated that many apparent false positives had plausible molecular rationales, consistent with a distinction between molecular mechanism disruption and clinical penetrance. Applied to KRAS, TDP-43, and BRCA1, the same channels capture the dominant pathogenic mechanisms in each protein as a proof of principle, while residual missed variants name specific gates yet to be written. The framework is distributed as the open-source Python package pathogenicity-gates (v0.5.1, MIT). These results show that a substantial fraction of full-length TP53 missense variation can be resolved through explicit, auditable physical gates that carry meaning beyond TP53, with each remaining failure naming the next rule to be written.

16.
arXiv (CS.CL) 2026-06-12

C-QUERI: Congressional Questions, Exchanges, and Responses in Institutions Dataset

Questions in political interviews and hearings serve strategic purposes beyond information gathering including advancing partisan narratives and shaping public perceptions. However, these strategic aspects remain understudied due to the lack of large-scale datasets for studying such discourse. Congressional hearings provide an especially rich and tractable site for studying political questioning: Interactions are structured by formal rules, witnesses are obliged to respond, and members with different political affiliations are guaranteed opportunities to ask questions, enabling comparisons of behaviors across the political spectrum. We develop a pipeline to extract question-answer pairs from unstructured hearing transcripts and construct a novel dataset of committee hearings from the 108th–117th Congress. Our analysis reveals systematic differences in questioning strategies across parties, by showing the party affiliation of questioners can be predicted from their questions alone. Our dataset and methods not only advance the study of congressional politics, but also provide a general framework for analyzing question-answering across interview-like settings.

17.
arXiv (CS.CV) 2026-06-11

SHERPA: Seam-aware Harmonized ERP Adaptation for Open-Domain 360$^\circ$ Panorama Generation

Panoramic imagery is increasingly used in world-generation, games, and simulation, where users may need not only photorealistic scenes but also stylized and non-photorealistic environments. Large-scale text-to-image diffusion and flow models provide broad style and semantic priors for this goal, but planar image training misaligns them with the wrap-around topology and polar regions of $360^\circ$ panoramas represented in equirectangular projection (ERP). We present SHERPA, a lightweight adaptation framework that combines frequency-selective Circular RoPE, Circular Latent Encoding/Decoding, image-side FFN adapters, and a Dual-Path Training Scheme. Circular RoPE replaces only the seam-sensitive high-frequency horizontal RoPE band with integer-periodic harmonics while preserving the pretrained lower-frequency spectrum. The Paired Panorama Path supervises geometry, while the Unpaired Style Path uses self-supervised yaw consistency for target-free stylized prompts. As a result, SHERPA generates $360^\circ$ panoramas across both photorealistic panorama domains and open-domain stylized prompts.

18.
bioRxiv (Bioinfo) 2026-06-18

Structure Bioinformatics of Eight Human ATP Synthase Fo Subunits and Their AlphaFold3-Predicted Water-Soluble QTY Analogs

Human mitochondrial ATP synthase is an essential rotary motor enzyme that produces most of the cellular ATP through oxidative phosphorylation. Its membrane-embedded Fo sector contains highly hydrophobic transmembrane subunits that are challenging to study in aqueous environments without detergents. This study explores whether applying the QTY code can reduce the hydrophobicity of selected ATP synthase Fo subunits while preserving their overall molecular structures. We applied the QTY code to eight human ATP synthase Fo subunits: ATP6, ATP8, ATPK, ATP68, ATPMK, AT5G1, AT5G2, and AT5G3. Hydrophobic amino acids leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in transmembrane regions were systematically replaced with hydrophilic glutamine (Q), threonine (T), and tyrosine (Y). Four native subunits with available CryoEM structures from human ATP synthase (PDB: 8H9S) were superposed with their AlphaFold3-predicted QTY analogs. The native ATP synthase Fo subunits superposed well with their respective QTY analogs. For the CryoEM-native comparisons, RMSD values ranged from 0.565[A] to 2.546[A]. For the AlphaFold3-native comparisons of subunits without CryoEM structures, RMSD values ranged from 0.204[A] to 0.297[A]. Despite substantial QTY substitutions in the transmembrane regions, ranging from 38.89% to 50.79%, the QTY analogs retained similar overall folds, molecular weights, and isoelectric points. Hydrophobic surface analysis showed that the QTY analogs had reduced hydrophobic patches compared with their native counterparts, with average hydrophobicity decreasing from 0.2959 in native proteins to -1.1023 in QTY analogs. These structural bioinformatics studies suggest that the QTY code can be applied to ATP synthase Fo subunits to generate more hydrophilic, potentially water-soluble analogs while preserving overall structural similarity. These results extend the application of the QTY code to the membrane-embedded Fo sector of ATP synthase and provide a foundation for future experimental studies testing whether these QTY analogs can be expressed, purified, and evaluated for assembly or proton-transfer-related functions.

19.
medRxiv (Medicine) 2026-06-15

Genome-wide colocalization of body fat distribution GWAS and subcutaneous adipose eQTLs identifies SNX10, DGKQ, and CBX3 as candidate causal genes for cardiometabolic disease

Authors:

Background: Genome-wide association studies (GWAS) have identified hundreds of loci associated with body fat distribution, yet the causal genes and regulatory mechanisms through which these variants exert their effects remain largely unknown. Expression quantitative trait locus (eQTL) colocalization provides a powerful framework for identifying genes whose expression is genetically coregulated with complex traits. Methods: We performed a genome-wide colocalization analysis integrating waist-hip ratio adjusted for body mass index (WHRadjBMI) GWAS summary statistics from 694,649 individuals (Pulit et al., 2019) with subcutaneous adipose tissue eQTLs from the Genotype-Tissue Expression (GTEx) Project v8 (N = 581 donors). GWAS coordinates were lifted from GRCh37 to GRCh38 to enable direct alignment with GTEx data. We incorporated CAVIAR fine-mapping results to overcome the limitation of FDR-significant eQTL filtering. Colocalization was assessed using the approximate Bayes factor framework (coloc.abf) across 335 independent genome-wide significant loci. Results: Of 2,897 locus-gene pairs tested, 489 (16.9%) showed strong colocalization (PP.H4 > 0.8) and 618 (21.3%) showed moderate evidence (PP.H4 > 0.5). The strongest colocalization was observed for SNX10 (sorting nexin 10; PP.H4 = 1.000), a recently characterized regulator of adipocyte differentiation and female-specific diet-induced obesity. Other top hits included DGKQ (diacylglycerol kinase theta; PP.H4 = 0.9999999), an emerging pharmacological target for insulin resistance, and CBX3 (chromobox 3; PP.H4 = 0.9999974), an epigenetic regulator linked to cardiovascular disease. Established adiposity genes including GRB14 (PP.H4 = 0.681) and KLF14 (PP.H4 = 0.590) were recovered, validating our approach. Several loci exhibited extensive allelic heterogeneity, with 50 genes colocalizing at a single chromosome 3 locus. Conclusions: Our analysis provides a comprehensive map of adipose tissue gene regulatory mechanisms underlying genetic risk for body fat distribution. The identification of SNX10, DGKQ, and CBX3 as high-confidence candidate causal genes advances the translation of GWAS associations into mechanistic understanding and therapeutic targets for obesity-related cardiometabolic disease.

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

Deep Unfolded Latent Optimally Partitioned-l2/l1 Networks for Data-driven Block-Sparse Recovery

arXiv:2606.12740v1 Announce Type: new Abstract: The convex Latent Optimal Partition (LOP)-l2/l1 approach enables block-sparse signal recovery with unknown partitions but relies on manual hyperparameter tuning. Additionally, numerical instability in differentiating its proximal operator prevents its automatic parameter tuning via Deep Unfolding (DU). To address these limitations, we propose two architectures: a stable framework utilizing implicit differentiation and a flexible variant leveraging Deep Weight Factorization (DWF). The DWF-based approach also supports nonconvex smooth data fidelity terms. Numerical experiments demonstrate that DU-LOP-l2/l1 yields competitive performance and high resilience against impulsive noise.

21.
arXiv (CS.AI) 2026-06-15

Hierarchical ODE: Learning Continuous-Time Physical Prototypes for Early Link Failure Detection

arXiv:2606.14284v1 Announce Type: cross Abstract: Time series prototype learning is fundamentally challenged by observational ambiguity. Discrete architectures fail to resolve this, as they lack the capacity to decouple stochastic noise from continuous dynamics. Furthermore, rigid closed-set assumptions fail to capture unseen diversity. To address these limitations, we propose a hierarchical ordinary differential equation clustering network, which utilizes neural ordinary differential equation to model latent state evolution as a continuous integral curve. This formulation enforces temporal continuity to effectively disentangle smooth feature trends from stochastic noise, while our adaptive hierarchical mechanism autonomously determines the appropriate number of prototypes without rigid prior constraints. Validated on the early link failure detection task with irregularly sampled time series, the proposed method effectively extracts underlying physical prototypes, thereby enabling robust failure detection. Our code is available at https://github.com/NJ-LNN/Hierarchical-ODE.

22.
arXiv (CS.AI) 2026-06-16

HOLO-MPPI: Multi-Scenario Motion Planning via Hierarchical Policy Optimization

arXiv:2606.16480v1 Announce Type: cross Abstract: Robots deployed in the real world must plan motions across diverse scenarios without per-scenario retuning. End-to-end reinforcement learning (RL) can generalize across scenarios but often becomes brittle under distribution shift, reward misspecification, and stochastic interactions. Model predictive path integral (MPPI) control enables strong real-time refinement without gradients, but its performance depends on a well-shaped sampling prior, while manually designing the priors does not scale to multi-scenario deployment. We present HOLO-MPPI (High-level Offline, Low-level Online MPPI), a multi-scenario motion planning framework that combines high-level policy learning with low-level stochastic optimal control. Offline, we learn a high-level policy that proposes scenario-robust plans in an abstract action space, with a learned world model for online rollout. Online, the policy serves as a data-driven prior generator that parameterizes MPPI's sampling distribution conditioned on the current observation and goal. MPPI then optimizes low-level control sequences around this prior in real time to adapt to local disturbances. We instantiate HOLO-MPPI in autonomous driving by designing an effective high-level action space and tailored model architectures. Our evaluation across diverse driving scenarios shows that HOLO-MPPI improves upon MPPI and end-to-end RL baselines while maintaining real-time control.

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

R2RDreamer: 3D-aware Data Augmentation for Spatially-generalized 2D Manipulation Policies

Spatial generalization is critical for imitation-learned manipulation policies, but achieving it typically requires scaling demonstrations across diverse object poses, robot configurations, and camera viewpoints. Data augmentation from a few source demonstrations offers a practical alternative to costly real-world collection. Simulation-based augmentation can create controllable variation, but requires complex environment and object setup and may introduce a sim-to-real gap. Recent real-to-real methods avoid these issues by jointly editing 3D observations and action trajectories from real demonstrations, yet they still rely on strong 3D scene parsing and geometry completion, and often produce observations tailored to 3D pointcloud policies rather than RGB-based 2D policies. We propose R2RDreamer, a real-to-real demonstration augmentation framework that preserves the geometric consistency of 3D action-observation editing while moving visual completion to 2D video space. Specifically, R2RDreamer first performs lightweight 3D augmentation by editing incomplete object pointclouds and end-effector trajectories in a shared 3D frame; it then projects the edited scene into masked image-space control videos with occlusion-aware reasoning and uses a dense-control image-to-video model to complete temporally coherent RGB observations. Experiments on spatially shifted manipulation tasks with both 2D diffusion-style policies and vision-language-action policies show that R2RDreamer improves spatial generalization from limited source demonstrations, with analyses validating the contributions of 3D editing, occlusion-aware projection, and video completion.

25.
arXiv (CS.AI) 2026-06-11

Planning under Distribution Shifts with Causal POMDPs

arXiv:2602.23545v2 Announce Type: replace Abstract: In the real world, planning is often challenged by distribution shifts. As such, a model of the environment obtained under one set of conditions may no longer remain valid as the distribution of states or the environment dynamics change, which in turn causes previously learned strategies to fail. In this work, we propose a theoretical framework for planning under partial observability using Partially Observable Markov Decision Processes (POMDPs) formulated using causal knowledge. By representing shifts in the environment as interventions on this causal POMDP, the framework enables evaluating plans under hypothesized changes and actively identifying which components of the environment have been altered. We show how to maintain and update a belief over both the latent state and the underlying domain, and we prove that the value function remains piecewise linear and convex (PWLC) in this augmented belief space. Preservation of PWLC under distribution shifts has the advantage of maintaining the tractability of planning via $\alpha$-vector-based POMDP methods.