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

Graph Learning Should Move Beyond Restrictive Views of Spectral and Message-Passing GNNs

arXiv:2602.10031v2 Announce Type: replace Abstract: Graph neural networks (GNNs) are commonly divided into message-passing neural networks (MPNNs) and spectral GNNs, reflecting two largely separate research traditions in machine learning and signal processing. While MPNNs have a precise definition, there is no widely accepted criterion for what makes a mapping a spectral GNN. Most existing work restricts spectral GNNs to layered architectures based on linear spectral filters. Under this restriction, we show that spectral and spatial GNNs have largely equivalent expressive power. To promote progress in the field, we propose a precise definition of spectral GNNs based on eigenbasis symmetries, in contrast to the definition of MPNNs via neighborhood permutation symmetries. We further argue that the two perspectives offer complementary strengths. MPNNs provide a natural language for discrete structure and expressivity analysis through tools from logic and graph isomorphism, while the spectral perspective offers principled tools for understanding smoothing, bottlenecks, stability, and community structure. Overall, we argue that progress in graph learning will be accelerated by clarifying the similarities and differences between these perspectives and by moving toward a unified theoretical framework.

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

Mirror Descent on Riemannian Manifolds

arXiv:2603.17527v2 Announce Type: replace-cross Abstract: Mirror Descent (MD) is a scalable first-order method widely used in large-scale optimization, with applications in image processing, policy optimization, and neural network training. This paper generalizes MD to optimization on Riemannian manifolds. In particular, we develop a Riemannian Mirror Descent (RMD) framework via reparameterization and further propose a stochastic variant of RMD. We also establish non-asymptotic convergence guarantees for both RMD and stochastic RMD. As an application to the Stiefel manifold, our RMD framework reduces to the Curvilinear Gradient Descent (CGD) method proposed in [26]. Moreover, when specializing the stochastic RMD framework to the Stiefel setting, we obtain a stochastic extension of CGD, which effectively addresses large-scale manifold optimization problems.

03.
medRxiv (Medicine) 2026-06-11

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

04.
arXiv (quant-ph) 2026-06-17

Manipulation of Topological Corner States via Subchiral Symmetry

arXiv:2606.17975v1 Announce Type: new Abstract: Higher-order topological phases provide robust corner modes, but their use requires controllable creation, isolation, and transfer of individual modes and their superpositions. Here we demonstrate, using the two-dimensional Benalcazar-Bernevig-Hughes model as an example, that subchiral symmetry provides a general control principle for manipulating topological corner modes. The conventional chiral symmetry decomposes into four subchiral symmetries, each associated with one zero-energy corner mode. By selectively breaking these subsymmetries with controlled intercell hoppings, we reduce the fourfold corner-state manifold step by step to single isolated modes. We further design adiabatic protocols that transfer either a single corner state or a superposition of two corner states between selected corners, while preserving the relative phase in the latter case. Both numerical simulations and IBM quantum-processor implementations show that the proposed protocols can be executed with high fidelity, establishing subchiral symmetry as a route to programmable higher-order topological state manipulation.

05.
arXiv (CS.LG) 2026-06-18

Toward Simultaneously Optimal Regret in U-Calibration

arXiv:2606.18527v1 Announce Type: cross Abstract: U-calibration studies online forecasting algorithms whose predictions can be consumed by any unknown downstream agent, guaranteeing sublinear regret simultaneously for all proper loss functions. Existing U-calibration algorithms achieve worst-case optimal $O(\sqrt{T})$ regret for every bounded proper loss, but they fail to adapt to easier losses: as we show, even for smooth losses such as squared loss, they incur $\Omega(\sqrt{T})$ regret instead of the optimal $O(\log T)$ regret. In this work, we show that this limitation is not inherent. Specifically, we design a single forecast algorithm that simultaneously achieves $\tilde O(\sqrt{T})$ regret for every bounded proper loss and $O(\log T)$ regret for every bounded smooth proper loss. More generally, our algorithm also attains logarithmic regret for losses that are smooth relative to the log-barrier, which include several non-Lipschitz examples. Our approach is based on a novel variant of Follow-the-Perturbed-Leader (FTPL) in which perturbations are applied directly in the prediction space using self-concordant noise. The resulting analysis also departs substantially from prior FTPL analyses due to the complex nature of this noise and may be of independent interest.

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

Revealing Hidden Vulnerabilities in Autoencoders through Gradient Signal Restoration

Adversarial robustness of deep autoencoders (AEs) has received less attention than that of discriminative models, although their compressed latent representations induce ill-conditioned mappings that can amplify small input perturbations and destabilize reconstructions. Existing white-box attacks for AEs, which optimize norm-bounded adversarial perturbations to maximize reconstruction damage, often converge to suboptimal perturbations, thereby potentially overstating AE robustness. We show that this limitation is linked to vanishing adversarial loss gradients during backpropagation through ill-conditioned layers, associated with near-zero singular values in their intermediate weight matrices. To address this, we propose GRILL (Gradient Signal Restoration in Ill-Conditioned Layers), a framework designed to mitigate gradient degradation and improve the reliability of adversarial robustness evaluation in encoder-decoder architectures. GRILL is designed to mitigate adversarial gradient degradation during optimization, enabling attacks to better approximate high-distortion perturbations under fixed norm constraints. Through extensive experiments across multiple AE architectures, under both sample-specific and universal attacks, as well as standard and adaptive attack settings, we show that GRILL significantly increases attack effectiveness, thereby exposing vulnerabilities hidden by existing attack limitations. Beyond AEs, we provide preliminary evidence that modern multimodal encoder-decoder architectures exhibit similar vulnerabilities.

07.
Nature (Science) 2026-06-10

Confirmation that bryozoan animals were present during the Cambrian explosion

Authors: Unknown Author

Bryozoans are marine invertebrates that live in colonies and have long been considered absent from the Cambrian explosion — a rapid evolutionary event that began around 538 million years ago. Newly discovered fossils from the Cambrian period reveal that the bryozoan phylum had already diversified by this time. Fossils of two forms of bryozoans show evidence of soft tissue still preserved inside their mineralized skeletons.

08.
arXiv (CS.CV) 2026-06-18

BrainFusionNet: a deep learning and XAI model to understand local, global, and sequential features of MRI images for improved brain tumour detection

The noise of Magnetic Resonance Imaging MRI poses challenges for Deep Learning DL when tumor boundaries are obscured tumor location and appearance are complex Therefore we develop BrainFusionNet that combines Convolutional Neural Networks CNNs Vision Transformers ViT and Gated Recurrent Units GRUs to extract spatial contextual and sequential features from MRI images for improved brain tumor classification Furthermore explainable AI such as SHAP LIME and GradCAM are integrated to visualise and highlight image regions that contribute to BrainFusionNets decisionmaking process The proposed BrainFusionNet model is evaluated on two publicly available MRI datasets Kfold validation suggests 98 accuracy on both datasets The model was compared with the six stateoftheart SOTA CNNs and transfer learning Among the SOTA CNNs DenseNet121 and VGG16 achieved the highest accuracy of 96 The novelty of BrainFusionNet is that the hybrid model effectively extracts local and global features from MRI images even in smallscale tumor regions and small tumor sizes The model has a balanced sequential CNN architecture to capture lowlevel and deeperlayer features a customized ViT that captures local features stabilizes gradient flow and reduces the risk of vanishing gradients during MRI image training The CNN and ViT outputs are fed into a GRU for final classification Furthermore we analyze pixel intensities to determine whether MRI image quality affects image classification Our findings are very novel in image interpretation as we found that the distribution of pixel intensities in MRI images affects DL performance

09.
arXiv (math.PR) 2026-06-24

Autoregressive Processes on Riemannian Manifolds

arXiv:2606.24771v1 Announce Type: cross Abstract: This paper introduces a Riemannian autoregressive (R-AR) model of order one, generalising classical discrete-time stochastic processes to manifold-valued data. The model is based on two parameters, a parameter $\mu$ representing the intrinsic central tendency as the Fréchet mean and an autoregressive parameter $\phi$ controlling the stationarity and ergodic properties. Due to the inherent dependence structure of the R-AR process, the estimation procedure for these parameters necessitates new asymptotic results for dependent processes on manifolds. Thus, we establish a strong law of large numbers for the sample Fréchet mean set of ergodic Markov chains in proper metric spaces. By proving this general consistency result, we move beyond the limitations of classical i.i.d. theory to provide the mathematical foundation required for the strong consistency of our proposed estimators. The framework is validated through numerical simulations in the hyperbolic plane and an application to aerosol size distributions on the Fisher-Rao manifold, demonstrating how the proposed model can characterise mean-reverting dynamics in nonlinear geometries.

10.
arXiv (math.PR) 2026-06-16

The existence of invariant sublinear expectations for $G$-SDEs

arXiv:2606.15203v1 Announce Type: new Abstract: In this paper, we study the existence of invariant sublinear expectations of Markovian semigroups on sublinear expectation spaces. To achieve this, we establish a complete metric space of sublinear expectations, on which we extend Harris' method to the nonlinear setting on the convergence of sublinear semigroups. We then explore two cases of $G-$diffusions by studying the Lyapunov function and the local Doeblin condition. One is the $G-$Brownian motion on the unit circle which is the case studied in Feng and Zhao [Zhaonon], but with the new method. Another is the multidimensional $G-$SDEs on the whole space $\mathbb{R}^d$. We establish, for the first time in the literature, the existence of the invariant sublinear expectation for $G-$SDEs under the non-degenerate and weakly dissipative assumption. For this, we prove that for a class of $G-$SDEs, the $G-$expectation can be represented as the supremum of the semigroup of a family of SDEs, of which the regularity is obtained by considering the Bismut-Elworthy-Li formula and the Denis-Hu-Peng representation for the distribution of $G-$Brownian motions.

11.
medRxiv (Medicine) 2026-06-23

Associations Between Social Responsiveness and Sleep Disruption are Modulated by Chronotype in Early Adolescence: Cross-Sectional and Prospective Findings from 10,108 Participants of the Adolescent Brain and Cognitive Development (ABCD) Study

Background: Sleep disruption is prevalent in people with neurodevelopmental disorders such as autism but is not clear whether it occurs as an endophenotype or secondary to other behaviours. The ABCD Study is a population-based longitudinal study that monitors the health, demography and lifestyle of over 11,000 children in the US. In this study we leverage these data to investigate whether traits consistent with autism (social responsiveness) are associated with sleep disruption independent of lifestyle and other behavioural measures. Methods: Autistic traits were assessed using the Social Responsiveness Scale at age 11, and sleep disruption and behavioural outcomes were assessed at ages 11 and 13 years using the Sleep Disturbance Scale, and the Child Behaviour Check List, respectively. Demographic, health and lifestyle-related variables were assessed by caregiver questionnaires. Regression models were applied to investigate associations between autistic traits and sleep outcomes. Results: There was a significant cross-sectional association between sleep disturbance and SRS at age 11 years old that was independent of sex, ethnicity, socioeconomic position, physical activity, sedentary behaviour and anxiety/depression ({beta} = 0.12, 95% CI (0.07, 0.17); p < 0.001), that persisted at age 13, and that was modulated by chronotype, with evening types showing a stronger association. Discussion: Social responsiveness assessed in early adolescence (age 11) were associated with sleep disruption independent of multiple confounding factors and were prospectively associated with sleep disruption at age 13 years. These findings contribute to the evidence that disruption of sleep and circadian timing may have a primary role in the neurobiological mechanisms that mediate autistic traits.

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

Let LLMs Judge Each Other: Multi-Agent Peer-Reviewed Reasoning for Medical Question Answering

Objective: To enhance the accuracy, interpretability, and robustness of large language models (LLMs) in medical question answering (MedQA). Method: We designed a multi-agent peer-reviewed reasoning method in which multiple LLM agents independently generate chain-of-thought reasoning with candidate answers, then act as peer reviewers to evaluate each other's reasoning for factual correctness and logical soundness. The highest-rated reasoning chain is selected to produce the final answer. Experiments were conducted with five state-of-the-art LLMs (Llama-3.1-8B, Qwen2.5-7B, Phi-4, DeepSeek-LLM-7B, GPT-oss-20B) on three benchmark datasets: HeadQA, MedQA-USMLE, and PubMedQA. Performance was compared against single-model chain-of-thought reasoning and chain-of-thought-based majority voting. Results: Peer-reviewed reasoning consistently outperformed both baselines. The best model combination achieved an average accuracy of 0.820 across datasets, exceeding the strongest single model (0.777) and majority voting ensembles (up to 0.789). The method also scaled effectively with more participating models, while peer assessments reliably distinguished high- from low-quality reasoning chains. Conclusion: The proposed multi-agent peer-reviewed reasoning method enables LLMs to act as both solvers and evaluators, yielding superior performance in MedQA. By emphasizing reasoning quality rather than answer agreement alone, this approach improves accuracy, interpretability, and robustness, offering a promising direction for trustworthy biomedical AI systems.

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

Localizing Credit at the Divergence: Path-Conditioned Self-Distillation for LLM Reasoning

arXiv:2606.15576v1 Announce Type: cross Abstract: Reinforcement learning from verifiable rewards assigns a single scalar to each rollout, leaving token-level credit assignment underspecified in long reasoning traces. On-policy self-distillation addresses this by letting the same model act as a teacher conditioned on privileged information, producing a dense per-token signal. But the common choice of a ground-truth answer is only an endpoint cue: on terse-answer tasks, the teacher falls silent at the intermediate positions where path-level guidance matters most. We propose Hindsight Self-Distillation (HSD), which conditions the teacher on a successful peer rollout drawn from the current training group. Such a peer is an exact sample from the success-conditioned policy, requiring no additional sampled rollouts. By providing a full successful continuation rather than only the final answer, the resulting credit signal concentrates at the divergence position between a failed rollout and a successful peer. Across Qwen3-8B and Qwen3-32B on math and code benchmarks, HSD obtains the best result against GRPO variants and on-policy distillation baselines, with the largest gains on terse-answer tasks such as AIME.

14.
arXiv (CS.CL) 2026-06-19

Segment-Level Mandarin Chinese Speech-Based Cognitive Impairment Detection via an Autoencoder with Contrastive Learning

\noindentBackground and Objective: Speech has emerged as a low-cost and non-invasive digital biomarker with considerable potential for cognitive impairment detection. However, limited labeled data and cross-dataset variability remain major challenges for robust speech-based screening systems. \par\noindentMethods: We developed a segment-level representation learning framework for speech-based cognitive impairment detection. Speech recordings were divided into short segments and converted into spectrogram representations. To improve robustness under limited-data conditions, offline and online augmentation strategies were combined with autoencoder-based representation learning and contrastive objectives to enhance discriminative latent representations. \par\noindentResults: Experiments conducted on four independent Mandarin Chinese speech datasets demonstrated stable and competitive performance in both binary and three-class classification tasks, with particularly notable improvements in the clinically challenging three-class setting. Ablation studies further supported the effectiveness of the proposed framework. \par\noindentConclusions: The findings suggest that segment-level speech representation learning may provide a scalable and practical approach for cognitive impairment screening in resource-constrained clinical settings.

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

Dirac-Frenkel dynamics with inertia for nonlinearly parametrized solutions of evolution problems

arXiv:2606.24769v1 Announce Type: cross Abstract: Even when Dirac-Frenkel dynamics determine a well-defined evolution in function space, the corresponding parameter dynamics can be non-unique or ill-conditioned for redundant nonlinear parametrizations such as neural networks or mixture models. We propose to add inertia to the Dirac-Frenkel dynamics and show that this allows useful parameter velocity information to persist from the past trajectory in directions that are weakly informed, while well-informed parameter velocity directions continue to follow the Dirac-Frenkel dynamics. We prove that the inertial formulation yields well-posed parameter dynamics and provide a posteriori error bounds. After time discretization, the method requires the solution of the same type of regularized linear least-squares problem as standard Dirac-Frenkel dynamics, but with the previous velocity appearing as an anchor. Numerical experiments demonstrate the increased robustness obtained with inertia.

16.
arXiv (CS.CV) 2026-06-19

Contour-Constrained Deformable Registration with Parameter Characterization for Head and Neck Surgical Guidance

With 890,000 annual new cases globally, head and neck squamous cell carcinoma has one of the highest recurrence rates among solid malignancies. Although frozen section analysis is the standard of care for intraoperative margin assessment, accurately relocating detected positive margins on the resection bed remains challenging due to imprecise alignment between resected specimens and their resection bed, compounded by post-resection mucosal tissue shrinkage. We present a biomechanics-driven deformable registration framework that corrects post-resection tissue deformation to provide intraoperative guidance. Our approach registers 3D specimen meshes to intraoperative resection bed point clouds using a deformable registration approach based on regularized Kelvinlet basis functions. The registration matches surface point clouds, fiducial landmarks, and boundary contour constraints that directly penalize perpendicular distance-to-agreement between specimen and resection bed boundaries. Across nine specimens from skin, buccal mucosa, and tongue sites, the overall mean target registration error was $11.11 \pm 4.07$ mm using rigid registration, which decreased to $8.20 \pm 2.68$ mm (26.19\% reduction) using deformable registration without contour constraint. The proposed contour-constrained deformable registration further reduced the error to $5.62 \pm 2.28$ mm, a 49.41\% reduction relative to rigid registration. We observed the largest reduction in the most clinically challenging tongue specimens. We also performed a systematic two-stage parameter search to characterize the relative importance of surface alignment, fiducial correspondences, contour constraint, and strain energy regularization. This search revealed that contour weighting dominates registration accuracy for tissue types with large lateral deformation, while the algorithm operates over a broad range of parameter combinations.

17.
arXiv (CS.AI) 2026-06-12

TWLA: Achieving Ternary Weights and Low-Bit Activations for LLMs via Post-Training Quantization

arXiv:2606.13054v1 Announce Type: cross Abstract: Large language models (LLMs) exhibit exceptional general language processing capabilities, but their memory and compute costs hinder deployment. Ternarization has emerged as a promising compression technique, offering significant reductions in model size and inference complexity. However, existing methods struggle with heavy-tailed activation distributions and therefore keep activations in high precision, fundamentally limiting end-to-end inference acceleration. To overcome this limitation, we propose TWLA, a post-training quantization (PTQ) framework that achieves 1.58-bit weight compression and 4-bit activation quantization while maintaining high accuracy. TWLA comprises three components: (1) Euclidean-to-Manifold Asymmetric Ternary Quantizer (E2M-ATQ) minimizes layer-output error under weight ternarization via a two-stage optimization from Euclidean initialization to manifold relocation; (2) Kronecker Orthogonal Tri-Modal Shaping (KOTMS) applies a Kronecker-structured orthogonal rotation to reshape weights into ternary-friendly tri-modal distributions, while the shared rotation statistically suppresses activation outliers; and (3) Inter-Layer Aware Activation Mixed Precision (ILA-AMP) explicitly introduces adjacent-layer second-order interaction costs in bit allocation and jointly optimizes for the layer-wise disparity of activation quantization gains induced by the shared orthogonal transform, preventing cascades triggered by a few weak layers. Extensive experiments demonstrate that TWLA maintains high accuracy under W1.58A4, while delivering significant inference acceleration. The code is available at .

18.
arXiv (CS.LG) 2026-06-24

Stochastic Expectation Maximization for Robust State-Space Radio Interferometric Imaging

arXiv:2606.23944v1 Announce Type: cross Abstract: State–space models provide a flexible framework for analyzing dynamical systems, yet they often rely on Gaussian assumptions that fail to capture heavy-tailed or outlier-prone measurement noise. We propose a robust estimation scheme for linear state–space models subject to compound-Gaussian noise, as encountered for instance in radio interferometry affected by radio-frequency interference (RFI). The method relies on a Stochastic Approximation Expectation–Maximization (SAEM) algorithm in which the standard E-step is replaced by Monte Carlo sampling of the latent states and noise texture through closed-form Gibbs updates, enabling tractable inference despite the heavy-tailed likelihood. Numerical experiments show that the proposed method significantly improves reconstruction fidelity and robustness to RFI, outperforming a Gaussian EM algorithm and even an oracle RTS smoother. These results highlight the benefits of heavy-tailed state–space modeling and SAEM-based inference in interference-dominated imaging scenarios.

19.
medRxiv (Medicine) 2026-06-11

Conversational Speech for Respiratory Triage in Primary Care: A Pilot Study

Authors:

Background. Respiratory complaints account for a substantial share of adult ambulatory care visits, and triaging them accurately has direct consequences for antibiotic stewardship and pathogen-specific therapy. Prior work has investigated voice as a triage signal, but that literature is dominated by single-condition detection from scripted speech in crowdsourced or controlled clinical settings and has not been evaluated at primary care scale on conversational ambient audio. Methods. A dataset of 514,377 ambient-recorded primary care visits from 379,225 adult patients at a US clinic network was used, with per-visit clinically assigned ICD-10 diagnosis codes and de-identified demographic and geographic metadata. Patient audio was extracted from each doctor-patient conversation, and spectral, voice quality, and prosodic features were computed. Eleven binary classification tasks were defined, aligned with a respiratory triage cascade (e.g., acute respiratory versus acute non-respiratory illness, and lower versus upper respiratory tract infection). An acoustic model (feed-forward network) was trained independently for each task using patient-stratified five-fold cross-validation and evaluated on a held-out test set. Each task's model was also compared against six non-acoustic baselines using a single demographic, geographic, or temporal variable. The 11 trained classifiers were composed into a hierarchical cascade and illustrated as case studies on selected patients. Results. Test-set AUC across the 11 tasks ranged from 0.602 (95% CI: 0.588-0.614) to 0.745 (95% CI: 0.742-0.748), with a mean expected calibration error of 0.018. Six of eleven binaries outperformed all confounder baselines. Four binaries showed median within-stratum AUC of 0.62-0.70 when the confounder was held fixed, indicating acoustic discrimination beyond what the confounder alone explains. The exception was the pneumonia versus non-pneumonia lower respiratory tract infection binary, which failed against the patient-city confounder baseline, plausibly reflecting a clinic-level difference in ICD-10 coding. Conclusion. Conversational primary care audio carries acoustic signal that discriminates clinically meaningful respiratory contrasts. Absolute performance is moderate, but the conditions are stricter than prior work: conversational speech and differential-diagnosis contrasts among sick patients. This pilot study is a baseline for voice-based clinical AI moving beyond sick-versus-healthy detection toward differential-diagnosis panels and a proof-of-concept for hierarchical reasoning.

20.
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.

21.
arXiv (CS.CV) 2026-06-24

Spectral Evolution-Guided Token Pruning in Multimodal Large Language Models

Reducing visual token redundancy is critical for accelerating Multimodal Large Language Models (MLLMs) without degrading cross-modal reasoning performance. Existing token pruning methods typically rely on single-layer signals, such as attention scores or token similarities, which overlook the cross-layer transformation of visual representations and may exhibit positional bias in multimodal token sequences. To address this limitation, we propose a training-free token pruning framework based on Cross-Layer Spectral Evolution (CLSE). Instead of measuring token importance from single-layer feature magnitudes, CLSE quantifies how token representations evolve across Transformer layers in the frequency domain. This evolution reflects the transition from high-frequency structural details to low-frequency semantic abstractions. We observe that tokens with stronger spectral redistribution across layers are more likely to be semantically active and should therefore be preserved. By modeling cross-layer token dynamics, CLSE provides a stable importance criterion that mitigates positional bias. Extensive experiments on both image and video benchmarks demonstrate that CLSE achieves a superior trade-off between efficiency and accuracy under aggressive token reduction. Across multiple MLLMs, CLSE reduces FLOPs, KV cache memory, and latency while maintaining competitive or improved performance.

22.
arXiv (CS.CV) 2026-06-18

CABLE: Cloud-Assisted Bandwidth-efficient LMM-based Encoding for V2X Systems

Cloud-hosted large multimodal models (LMMs) can provide strong open-vocabulary perception for Vehicle-to-Everything systems, but naively transmitting full-resolution frames from edge to cloud causes severe communication overhead and high cloud-side prefill latency. We present CABLE, a cloud-assisted bandwidth-efficient LMM-based encoding framework for edge-cloud perception. CABLE propagates the previous cloud segmentation mask on the edge using ego-motion compensation, refines it with residual-motion cues, and consolidates disconnected regions via a corridor envelope to form a robust region of interest (ROI). Only ROI-masked images are uploaded, while the cloud segmentation output is fed back as the prior for the next frame, forming a mask-to-ROI-to-LMM feedback loop. Experiments on five datasets (nuScenes, WOD-ZB, Waymo, KITTI, and CADC) show consistent communication savings while largely preserving perception, achieving $73$–$87\%$ ROI pixel-coverage reduction with $5$–$8\times$ estimated LMM prefill speedup at a modest detection-quality trade-off relative to full-frame inference.

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

When Language Representations Interact: Separability and Cross-Lingual Effects in LLMs

arXiv:2606.14347v1 Announce Type: new Abstract: Large language models exhibit strong multilingual capabilities, however, their internal representations are difficult to interpret. Understanding these interactions is important for ensuring reliable behavior in multilingual systems. Recent work has shown that causal-geometric structure can explain how certain concepts are encoded as approximately linear and separable directions, but whether this framework extends to multilingual models, where language identity is correlated and hierarchical, is underexplored. We apply causal-geometric analysis to multilingual LLMs, studying 28 bilingual contrasts across three models, allowing us to analyze when languages behave as approximately independent factors and when structured dependencies persist. We find evidence that language concepts admit stable linear representations that are largely separable under a covariance-adjusted (causal) inner product, with structured deviations reflecting linguistic similarity. Moreover, languages within the same family (such as Germanic or Romance) exhibit a simplex-like geometric structure, suggesting hierarchical organization. These results extend causal-geometric interpretability to multilingual settings and provide insight into how separability and similarity may exist in multilingual LLM representations, motivating interpretability analyses that diagnose when and how structured dependencies between concepts can be anticipated. This has implications for trustworthy deployment, as residual structure between languages may lead to unintended cross-lingual effects when models are monitored or intervened upon.

24.
arXiv (CS.CV) 2026-06-12

PROBE: Probabilistic Occupancy BEV Encoding with Analytical Translation Robustness for 3D Place Recognition

We present PROBE (PRobabilistic Occupancy BEV Encoding), a learning-free LiDAR place recognition descriptor that models each BEV cell's occupancy as a Bernoulli random variable. Rather than relying on discrete point-cloud perturbations, PROBE analytically marginalizes over continuous Cartesian translations via the polar Jacobian, yielding a distance-adaptive angular uncertainty $\sigma_\theta = \sigma_t / r$ in $\mathcal{O}(R{\cdot}S)$ time. The primary parameter $\sigma_t$ represents the expected translational uncertainty in meters, a sensor-independent physical quantity that enhances cross-sensor generalization while reducing the need for extensive per-dataset tuning. Pairwise similarity combines a Bernoulli-KL Jaccard with exponential uncertainty gating and FFT-based height cosine similarity for rotation alignment. Evaluated on four datasets spanning four diverse LiDAR types, PROBE achieves the highest accuracy among handcrafted descriptors in multi-session evaluation and competitive single-session performance relative to both handcrafted and supervised baselines. The source code and supplementary materials are available at https://sites.google.com/view/probe-pr.

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

DeMix: Debugging Training Data with Mixed Data Error Types by Investigating Influence Vectors

arXiv:2606.11616v1 Announce Type: new Abstract: High-quality training data is essential for the success of machine learning models. However, real-world datasets often contain mixed types of errors arising from systematic flaws in data preparation pipelines, including label errors, feature errors, and spurious correlations. Effective debugging of training data requires both detecting erroneous samples and identifying their specific error types to enable targeted repair, yet existing data cleaning and attribution methods fail to adequately address this dual requirement. In this paper, we propose DeMix, a novel framework that simultaneously diagnoses erroneous samples and their error types. Our key insight is that different error types produce distinct patterns on model behavior. DeMix captures such error-specific patterns by influence vectors that characterize how each training sample affects model predictions across all validation samples. We formulate training data debugging as a multi-label classification problem where a classifier is developed to predict error types directly from influence vectors. We further introduce an intervention-based learning strategy that guides the classifier to capture invariant rationales specific to each error type, ensuring the learned classifier generalizes effectively. Empirical evaluations on 11 tasks across tabular data prediction, recommendation systems, and LLM alignment demonstrate that DeMix significantly outperforms state-of-the-art approaches, achieving a 22.61% improvement in data debugging F1-score and a 9.32% gain in task model performance after data repair. Code is available at: https://github.com/SJTU-DMTai/DeMix.