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01.
Nature (Science) 2026-06-08

Daily briefing: Human embryo genomes precisely altered

作者:
Flora Graham↗

The use of ‘base editing’ to precisely tweak human embryos has divided researchers. Plus, the number of lives saved by less-polluting cars in China and how to tip the world towards a sustainable future. The use of ‘base editing’ to precisely tweak human embryos has divided researchers. Plus, the number of lives saved by less-polluting cars in China and how to tip the world towards a sustainable future.

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

Proximal Policy Optimization for Amortized Discrete Sampling

作者:
Anna Zykova-Myzina↗Timofei Gritsaev↗Daniil Tiapkin↗Nikita Morozov↗

arXiv:2606.15793v1 Announce Type: cross Abstract: This paper explores policy gradient algorithms for training stochastic policies to sample from structured discrete probability distributions under the Generative Flow Network (GFlowNet) framework. Building on extensive theoretical connections between GFlowNets and entropy-regularized reinforcement learning, we derive equivalents of standard policy gradient algorithms for training GFlowNets, as well as experimentally explore their various methodological aspects, including baseline training and advantage estimation. Most importantly, our work is the first to derive and successfully apply proximal policy optimization to GFlowNets, showing its improved convergence speed and data efficiency compared to standard GFlowNet training objectives on benchmarks ranging from synthetic energies to molecular graph generation.

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

A Bayesian Boolean Matrix Factorization with Application to Copy Number Analysis in Cancer

作者:
Adolphus Wagala↗Mehmet Samur↗Giovanni Parmigiani↗

arXiv:2606.17491v1 Announce Type: cross Abstract: Binary data factorization is common, but real-valued methods ignore discreteness and yield hard-to-interpret factors. Boolean Matrix Factorization (BooMF) instead decomposes a binary matrix into two lower-rank binary matrices via logical AND and OR, expressing the data as a Boolean disjunction of interpretable patterns. In cancer genomics, BooMF can reveal coordinated feature changes that may drive tumor evolution, unlike rotational or additive decompositions. Most existing BooMF methods are heuristic, greedy, sensitive to initialization, prone to local optima, and do not support principled model selection or uncertainty quantification. We introduce Bayesian Boolean Matrix Factorization (BBMF), a fully conjugate generative model with sparsity-inducing priors. It enforces Boolean constraints, yields interpretable latent factors with coherent uncertainty quantification, and admits Gibbs sampling with closed-form full conditionals. Because cancer evolution often involves widespread, near-simultaneous chromosome-number changes (e.g., whole-genome duplication followed by instability and selection), Boolean factorizations capture these patterns more naturally than additive models. Applied to arm-level copy-number alteration data in multiple myeloma, where entries indicate presence/absence of chromosomal-arm amplifications, BBMF finds a small set of interpretable bicliques linking patient subsets to recurrently co-altered chromosomal arms, providing a compact, biologically meaningful summary of tumor heterogeneity and demonstrating BBMF's utility for uncovering discrete latent structure in complex binary data.

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

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

作者:
Po-Chin Chang↗Nicholas Hogan↗Aske Plaat↗Michiel T. van der Meer↗

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

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

Unsupervised Causal Abstractions Discovery

作者:
Th\'eo Saulus↗Simon Lacoste-Julien↗Dhanya Sridhar↗

arXiv:2606.19594v1 Announce Type: new Abstract: Causal abstractions formalize when a high-level structural causal model (SCM) captures the interventional behavior of a lower-level SCM. Existing applications of this notion largely follow a hypothesis-testing paradigm: an expert proposes a candidate high-level model and then evaluates if the low-level system implements it. We study the complementary problem of learning a high-level model directly from low-level measurements. Our contributions leverage hypotheses from low-rank causal discovery, and can be summarized as follows: (1) we show that observations generated by a low-rank graph induce latents that form a causal abstraction, (2) we provide identifiability results about these latents, and (3) we propose a practical objective to learn this high-level SCM.

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

LoRDO: Distributed Low-Rank Optimization with Infrequent Communication

作者:
Andrej Jovanovi\'c↗Alex Iacob↗Mher Safaryan↗Ionut-Vlad Modoranu↗Lorenzo Sani↗William F. Shen↗Xinchi Qiu↗Dan Alistarh↗Nicholas D. Lane↗

arXiv:2602.04396v2 Announce Type: replace-cross Abstract: Distributed training of foundation models via $\texttt{DDP}$ is limited by interconnect bandwidth. While infrequent communication strategies reduce synchronization frequency, they remain bottlenecked by the memory and communication requirements of optimizer states. Low-rank optimizers can alleviate these constraints; however, in the local-update regime, workers lack access to the full-batch gradients required to compute low-rank projections, which degrades performance. We propose $\texttt{LoRDO}$, a principled framework unifying low-rank optimization with infrequent synchronization. We first demonstrate that, while global projections based on pseudo-gradients are theoretically superior, they permanently restrict the optimization trajectory to a low-rank subspace. To restore subspace exploration, we introduce a full-rank quasi-hyperbolic update. $\texttt{LoRDO}$ achieves near-parity with low-rank $\texttt{DDP}$ in language modeling and downstream tasks at model scales of $125$M–$720$M, while reducing communication by $\approx 10 \times$. Finally, we show that $\texttt{LoRDO}$ improves performance even more in very low-memory settings with small rank/batch size.

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08.
arXiv (quant-ph) 2026-06-16

Learning ground state observables from quantum computing experiments

作者:
Ben Jaderberg↗Freya Shah↗Minjun Jeon↗M. Emre Sahin↗Christa Zoufal↗Kunal Sharma↗

arXiv:2606.15983v1 Announce Type: new Abstract: Recent theoretical progress has established conditions under which machine learning models can efficiently predict ground-state properties of gapped local Hamiltonians when trained on quantum-generated data. Previous experimental demonstrations in this paradigm, however, have largely been limited to small systems or highly structured states, due to the difficulty of preparing many-body ground states on quantum processors. In this work, we demonstrate learning from experimental quantum data generated from approximate ground states of the two-dimensional Heisenberg XXZ model with system sizes up to 115 qubits. We construct a dataset of single-site expectation values, two-point correlations, and 12-body loop correlations across the antiferromagnetic phase. We then train neural networks on this data and show that they can accurately predict spatially resolved observables for previously unseen Hamiltonian parameters, both within the training distribution and in an out-of-distribution regime approaching the phase boundary. Our results demonstrate the practical realization of learning from quantum data for an interacting two-dimensional many-body system at scale, motivating a path toward regimes where quantum processors could provide training data beyond the reach of classical approximation methods.

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09.
arXiv (CS.AI) 2026-06-15

FPGA-Based Neural Network Accelerators for Space Applications: A Survey

作者:
Pedro Antunes↗Artur Podobas↗

arXiv:2504.16173v3 Announce Type: replace-cross Abstract: Space missions are becoming increasingly ambitious, necessitating high-performance onboard spacecraft computing systems. In response, field-programmable gate arrays (FPGAs) have garnered significant interest due to their flexibility, cost-effectiveness, and radiation tolerance potential. Concurrently, neural networks (NNs) are being recognized for their capability to execute space mission tasks such as autonomous operations, sensor data analysis, and data compression. This survey serves as a valuable resource for researchers aiming to implement FPGA-based NN accelerators in space applications. By analyzing existing literature, identifying trends and gaps, and proposing future research directions, this work highlights the potential of these accelerators to enhance onboard computing systems.

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10.
arXiv (CS.LG) 2026-06-18

From Mechanistic to Compositional Interpretability

作者:
Ward Gauderis↗Thomas Dooms↗Steven T. Homer↗Kola Ayonrinde↗Geraint A. Wiggins↗

arXiv:2605.08934v2 Announce Type: replace Abstract: Mechanistic interpretability aims to explain neural model behaviour by reverse-engineering learned computational structure into human-understandable components. Without a formal framework, however, mechanistic explanations cannot be objectively verified, compared, or composed. We introduce compositional interpretability, a category-theoretic framework grounded in the principles of compositionality and minimum description length. Compositional interpretations are pairs of syntactic and semantic mappings that must commute to enforce consistency between a model's decomposition and its observed behaviour. We deconstruct explanation quality into measures of faithfulness and complexity to cast interpretability as a constrained optimisation problem, and introduce compressive refinement to systematically restructure models into simpler parts without altering their function. Finally, we derive a parsimony criterion under which syntactic compression theoretically guarantees more concise, human-aligned explanations. Our framework situates prominent mechanistic methods as subclasses of refinement, and clarifies why their compressibility heuristics tend to align with human interpretability. Our work provides a measurable, optimisable blueprint for automating the discovery and evaluation of mechanistic explanations.

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11.
arXiv (math.PR) 2026-06-18

Power Partitions and Hayman Functions

作者:
Jos\'e L. Fern\'andez↗V\'ictor J. Maci\'a↗

arXiv:2602.18575v3 Announce Type: replace Abstract: We prove, within the probabilistic framework of Khinchin families, that the generating function $P_k$ of partitions into $k$-th powers is strongly Gaussian in the sense of Báez-Duarte, and even further that it is a Hayman function. Thus the Hardy–Ramanujan asymptotic formula for the number $p_k(n)$ of partitions of $n$ into $k$-th powers which reads \[ p_k(n) \sim \frac{\alpha_k}{n^{(3k+1)/(2k+2)}} \exp\!\Big(\beta_k\, n^{1/(k+1)}\Big), \qquad n\to\infty, \] where $\alpha_k$ and~$\beta_k$ are explicit constants depending only on $k$, follows directly from Hayman's asymptotic formula for strongly Gaussian power series. The proof of strong Gaussianity of $P_k$ combines a Gaussianity criterion for Khinchin families with certain bounds of Tenenbaum, Wu and Li on the generating function; the asymptotic formula is recovered by computing asymptotic approximations of the mean and variance of the associated family. Analogous results are presented for the generating function $Q_k$ of partitions into distinct $k$-th powers.

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12.
arXiv (quant-ph) 2026-06-16

Complete Relational Description of Spin in a Quantum Background

作者:
Hannah Troger↗Ofek Bengyat↗Thomas D. Galley↗Marios Christodoulou↗

arXiv:2606.15873v1 Announce Type: new Abstract: The standard description of the state of a spin in quantum mechanics presupposes externally fixed directions – a classical background. Can a spin be fully described instead in relation to other quantum mechanical systems? Poulin suggested twenty years ago group averaging over rotations the joint state of a fundamental spin and a reference spin with large angular momentum which, however, yields a classical bit in a probabilistic mixture. We revisit this idea and show that when the quantum reference system is augmented to two large spins, the standard quantum mechanical description of a spin is recovered in the limit of large quantum numbers for the reference system.

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13.
arXiv (CS.LG) 2026-06-17

Recursive Learning Without Collapse: A Weighting-Based Stabilization Framework

作者:
Hengzhi He↗Shirong Xu↗Guang Cheng↗

arXiv:2502.18049v5 Announce Type: replace-cross Abstract: Recent studies identified an intriguing phenomenon in recursive generative model training known as model collapse, where models trained on data generated by previous models exhibit severe performance degradation. Addressing this issue and developing more effective training strategies have become central challenges in generative model research. In this paper, we investigate this phenomenon within a novel framework, where generative models are iteratively trained on a combination of newly collected real data and synthetic data from the previous training step. To develop an optimal training strategy for integrating real and synthetic data, we evaluate the performance of a weighted training scheme in various scenarios, including Gaussian distribution estimation, generalized linear models, and nonparametric estimation. We theoretically characterize the impact of the mixing proportion and weighting scheme of synthetic data on the final model's performance. Our key finding is that, across different settings, the optimal weighting scheme under different proportions of synthetic data asymptotically follows a unified expression, revealing a fundamental trade-off between leveraging synthetic data and model performance. In some cases, the optimal weight assigned to real data corresponds to the reciprocal of the golden ratio. Finally, we validate our theoretical results on extensive simulated datasets and a real tabular dataset.

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14.
arXiv (CS.CL) 2026-06-11

Hubs or Fringes: Pretraining Data Selection via Web Graph Centrality

作者:
Vedant Badoni↗Danqi Chen↗Xinyi Wang↗

The performance of modern language models depends critically on pretraining data composition. Yet existing data selection methods rely on auxiliary classifiers for document scoring or mixture optimization, adding computational overhead and dependence on labeled data. We propose WebGraphMix, a lightweight data selection framework that computes structural centrality scores over the Common Crawl host-level web graph and uses them to vary the proportion of central versus peripheral documents in the pretraining mixture. We hypothesize that central hosts expose models to reusable abstractions, while peripheral hosts encode specialized, long-tail knowledge. WebGraphMix computes centrality scores efficiently at web scale, requiring no model training, labeled data, or downstream supervision. We integrate WebGraphMix into the DataComp-LM pipeline and train models at 400M and 1B parameter scales with 8B and 28B tokens respectively, evaluating on 23 tasks ranging from factual knowledge to symbolic reasoning. Our experiments show that central and peripheral web regions encode complementary capabilities. Mixture combining both at a ratio of 1:1 achieves 41.4% on average, compared to 39.8% for uniform sampling. Combining structural scores with document-level quality classifier scores further improves performance to 43.8%. These findings demonstrate that web graph topology is a meaningful axis for pretraining data curation, capturing information that is largely orthogonal to existing content-based approaches.

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15.
medRxiv (Medicine) 2026-06-15

Mucosal and Systemic Antibodies Associated with Clinical Protection in a Pertussis Controlled Human Infection Model

作者:
Milletich↗P. L↗ElSherif↗M. S↗Marx↗Caulfield↗Hariri↗Halperin↗S. S↗Pasetti↗M. F↗

Background The engagement of mucosal and systemic immunity in preventing Bordetella pertussis colonization and infection in humans, the impact of prior vaccination on host immunity and protective outcomes, and the dynamics of the host response following exposure remain poorly understood. Methods Healthy adults were challenged with increasing colony-forming units (CFUs) doses, 106-108, of B. pertussis D420 intranasally (NCT05136599). Shedding (PCR and culturing) and symptom development were monitored up to 21 days post-challenge. Serum and nasal wash IgA and IgG were measured before challenge (baseline) and up to 6 months post-challenge. Findings Antibodies increased post-challenge only in infected individuals, primarily nasal IgA. Participants who remained uninfected had higher baseline levels of filamentous hemagglutinin (FHA)- specific mucosal IgA and IgG, and higher serum IgA against fimbriae 2/3 (FIM). FHA was negatively associated with bacterial load and was a key discriminator between shedders and non-shedders, up to one week post-challenge. By day 14 post-challenge, pertussis toxin (PT) IgG and FIM IgA in both serum and mucosal samples were negatively associated with bacterial colonization. The majority (96.7%) of acellular pertussis (aP) vaccine recipients (n=23, median age 2.0 years) became infected, compared to 69.4% of those who received whole-cell pertussis vaccine (n=36; median age 32.0 years), and their antibody responses remained distinct following infection. Interpretation Nasal FHA antibodies emerged as early predictors of protection against pertussis infection, while PT IgG and FIM IgA antibodies may reflect clearance after infection. aP-primed individuals were more susceptible to infection, despite their younger age and more recent vaccination. Funding CDC Contract #75D30122C15467 and CDC IPA Agreement #24IPA2417512 Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, US Department of Health and Human Services.

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16.
arXiv (CS.CL) 2026-06-15

Personal Care Utility: Health as Everyday Infrastructure

作者:
Mahyar Abbasian↗Elahe Khatibi↗Saba A. Farahani↗Nitish Nagesh↗Arshia Ilaty↗Hooman Sajjadi↗Amir Rahmani↗Ramesh Jain↗

Healthcare is essential, expert, and episodic by design - built around the roughly one hour per year a person spends with a clinician. The 8,759 hours outside clinical settings, where eating, sleeping, movement, medication, and stress actually shape long-term health, have no comparable infrastructure. The bottleneck for personalized health is not raw data or reasoning capability; it is the absence of that infrastructure layer. This paper introduces the Personal Care Utility (PCU): a layered, event-driven architecture proposed as the missing utility for everyday health, in the way that payments, networks, and power are utilities for their domains. PCU organizes continuous personal signals into semantically meaningful life events through a Personicle, estimates dynamic health state against personal baselines, reasons about cause and context, and routes guidance through an orchestrator that separates clinical decision logic, behavioral strategy selection, and natural-language expression. This separation lets large language models support reasoning and communication while keeping safety-critical clinical decisions grounded in validated evidence. We instantiate PCU for Type 2 Diabetes - turning CGM, meal, activity, medication, sleep, stress, and clinical data into glycemic events, individualized state estimates, causal explanations, and knowledge-grounded interventions. A day-in-the-life scenario shows the same infrastructure producing real-time nudges, weekly summaries, medication check-ins, silence, or deterministic safety alerts depending on context and risk. We close with how PCU generalizes to other chronic conditions and the governance questions any always-on personal health utility must address. The result is a blueprint that treats personalization not as a final messaging layer, but as an architectural property of everyday health guidance.

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17.
arXiv (CS.CV) 2026-06-16

FireRed-Image-Edit-1.0 Technical Report

作者:
Super Intelligence Team↗Changhao Qiao↗Chao Hui↗Chen Li↗Cunzheng Wang↗Dejia Song↗Jiale Zhang↗Jing Li↗Qiang Xiang↗Runqi Wang↗Shuang Sun↗Wei Zhu↗…

We present FireRed-Image-Edit, a diffusion transformer for instruction-based image editing that achieves state-of-the-art performance through systematic optimization of data curation, training methodology, and evaluation design. We construct a 1.6B-sample training corpus, comprising 900M text-to-image and 700M image editing pairs from diverse sources. After rigorous cleaning, stratification, auto-labeling, and two-stage filtering, we retain over 100M high-quality samples balanced between generation and editing, ensuring strong semantic coverage and instruction alignment. Our multi-stage training pipeline progressively builds editing capability via pre-training, supervised fine-tuning, and reinforcement learning. To improve data efficiency, we introduce a Multi-Condition Aware Bucket Sampler for variable-resolution batching and Stochastic Instruction Alignment with dynamic prompt re-indexing. To stabilize optimization and enhance controllability, we propose Asymmetric Gradient Optimization for DPO, DiffusionNFT with layout-aware OCR rewards for text editing, and a differentiable Consistency Loss for identity preservation. We further establish REDEdit-Bench, a comprehensive benchmark spanning 15 editing categories, including newly introduced beautification and low-level enhancement tasks. Extensive experiments on REDEdit-Bench and public benchmarks (ImgEdit and GEdit) demonstrate competitive or superior performance against both open-source and proprietary systems. To support future research, our code, models, and benchmark suite are publicly available at https://github.com/FireRedTeam/FireRed-Image-Edit/ .

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18.
arXiv (CS.CV) 2026-06-12

Heterogeneous LiDAR Early Fusion and Learned Re-Ranking Strategy for Robust Long-Term Place Recognition in Unstructured Environments

作者:
Judith Vilella-Cantos↗Juan Jos\'e Cabrera↗M\'onica Ballesta↗David Valiente↗Luis Pay\'a↗

Robust localization in unstructured environments, such as agricultural fields, is a critical challenge for autonomous systems. LiDAR sensors provide detailed 3D information about the environment and are invariant to lighting conditions. For this reason, LiDAR-based place recognition methods have gained significant attention. In this paper, we propose MinkUNeXt-VINE++, a novel approach that combines early fusion of heterogeneous LiDAR data from two sensors (Livox Mid-360 and Velodyne VLP-16) and a learned re-ranking strategy in inference time. This fusion leverages the strengths of each sensor to provide a more comprehensive representation of the environment. Additionally, the re-ranking approach is particularly important in repetitive environments, such as vineyards, as finding true positives is a major challenge. We evaluated our approach using the TEMPO-VINE dataset, which provides heterogeneous LiDAR data in vineyard environments across different phenological stages. Our results demonstrate that MinkUNeXt-VINE++ significantly improves place recognition performance compared to single-sensor approaches and state-of-the-art methods. MinkUNeXt-VINE++ achieves a 20% improvement in the Recall@1 metric compared to single-sensor approaches, and +30% including re-ranking. The code of our method is publicly available for reproduction.

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

Mitigating Content Shift and Hallucination in GenAI Image Editing via Structural Refinement

作者:
Luxi Zhao↗Michael S. Brown↗

Generative AI (GenAI) image editors, such as Nano Banana, produce visually compelling results for retouching tasks, enabling non-experts to edit images through text prompts alone. However, the generative nature of these models often introduces spatial misalignment, texture distortion, and content hallucination, all of which are detrimental to downstream workflows that require pixel-level fidelity. We identify a problem setting we call "structure-preserving GenAI fusion" for black-box GenAI image retouching: retain the perceptual enhancements of a GenAI output while enforcing structural faithfulness to the original input image. To address this problem, we propose a post-processing framework that fuses an input image with its GenAI-enhanced counterpart by first establishing coarse spatial and photometric correspondences, then performing a fusion stage that transfers desired enhancements while suppressing hallucinated content. In the absence of direct prior work in this setting, we evaluate our framework against representative methods from photorealistic style transfer and image fusion. Our experiments demonstrate that our method better preserves aesthetic quality while maintaining pixel-level structural consistency and the input resolution.

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

Prediction-Powered Causal Inference by Automatic Debiased Machine Learning and Semi-Supervised Riesz Regression

作者:
Masahiro Kato↗

arXiv:2606.12892v1 Announce Type: cross Abstract: This study investigates semiparametric efficient estimation of causal and structural parameters in a semi-supervised setting. In our setting, unlabeled auxiliary regressors are available in addition to labeled observations consisting of outcomes and regressors. Our goal is to construct estimators of causal and structural parameters whose asymptotic variances are smaller than those of estimators constructed using only labeled data. We refer to this framework as prediction-powered causal inference (PPCI). We first derive the efficient influence function and the efficiency bound, which imply that the use of auxiliary regressors can attain a smaller asymptotic variance than the efficiency bound attainable from labeled observations alone. Then, by combining the efficient influence function with the debiased machine learning (DML) framework, we propose methods that we call DML-PPCI. If we construct an estimating-equation estimator, we refer to the method as EE-DML-PPCI; if we construct a targeted-learning estimator, we refer to the method as TMLE-DML-PPCI. The asymptotic variances of both estimators match our derived efficiency bound. In the construction of the estimators, estimation of the efficient influence function plays an important role. In our study, the efficient influence function is also a Neyman orthogonal score, which depends on the Riesz representer and the regression function. For Riesz representer estimation, we develop semi-supervised generalized Riesz regression with convergence rate guarantees.

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21.
arXiv (CS.LG) 2026-06-19

Quantum-classical physics-informed Kolmogorov-Arnold networks for PDEs

作者:
Xiang Rao↗Yuxuan Shen↗

arXiv:2606.20326v1 Announce Type: new Abstract: We develop QCPIKAN, the first quantum-classical physics-informed Kolmogorov-Arnold network designed to solve partial differential equations (PDEs). Built upon Chebyshev-polynomial KAN layers and parameterized quantum circuits, this hybrid framework embeds physical constraints into the training loss to enforce physical consistency. Our theoretical investigations grounded in approximation theory prove that this design accelerates high-frequency error convergence to an exponential rate and effectively mitigates numerical dispersion. We validate the framework across three typical seepage scenarios in porous media, including single-phase flow, component transport and two-phase flow. Compared with existing quantum-classical physics-informed neural networks, QCPIKAN achieves superior performance in global prediction accuracy, local error control, dynamic evolution tracking and displacement front localization. This work provides a robust and efficient alternative for solving complex PDEs.

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22.
medRxiv (Medicine) 2026-06-19

Specific epigenetic age acceleration measures are associated with oral health outcomes in U.S. adults

作者:
Tang↗A. L↗Tsurumi↗

Objectives: Oral health conditions impact a significant proportion of the global population. Chronological age is a known risk factor; however, characterization of epigenetic age remains limited and is expected to provide additional insight into biological mechanisms. Materials and Methods: The National Health and Nutrition Examination Survey (NHANES) was used to analyze the effect of epigenetic age measures of DunedinPoAm, and epigenetic age acceleration (EAA) of Horvath, Hannum, Weidner, Lin, VidalBralo, PhenoAge, GrimAge, and GrimAge2, on various oral health outcomes from survey and examination results. Univariable and multivariable logistic regression were performed, adjusting for sex, race-ethnicity, education, poverty income ratio categories, and dental insurance coverage status. Results: DunedinPoAm was associated with the last dental appointment being for an existing issue (p=0.0093), poor general oral condition (p=0.0226), limiting food due to teeth problems (p=0.0031), and recommendation to see a dentist within the next two weeks (p=0.0171). EAAs for PhenoAge, GrimAge, and GrimAge2, were associated with a smaller number of oral health outcomes, whereas EAAs for Horvath, Hannum, Weidner, Lin, and Vidal-Bralo showed no associations. Conclusions: In a representative U.S. population, DunedinPoAm was most consistently positively associated with different adverse oral health outcomes compared with other epigenetic aging measures. Tracking specific epigenetic ages such as DunedinPoAm, EAA GrimAge, EAA GrimAge2, and PhenoAge, may aid in additional monitoring of oral health outcomes. Understanding specific aging-related CpGs associated with oral health may aid in elucidating underlying molecular mechanisms.

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23.
bioRxiv (Bioinfo) 2026-06-18

Accounting for allelic diversity and multicopy gene detection improves the accuracy of antibiotic resistance genotypic determination

作者:
Garcia Gonzalez↗Ferragud↗Blane↗Kim↗J. I↗Torok↗M. E↗Harrison↗E. M↗Gouliouris↗Coll↗

Background Genomic prediction of antimicrobial resistance (AMR) relies on the accurate detection of resistance genes or allelic variants of core genes from raw or assembled genomes sequences. For several bacterial species and antibiotics, AMR genotype-phenotype discrepancies are common, indicating that important sources of error remain unresolved. For Enterococcus faecium, we focused on identifying the sources of discrepancies for tetracycline resistance, for which genotypic detection had shown particularly low accuracy. We investigated the effect of structural variation in antibiotic resistance genes (ARGs), including gene duplications, truncations, interruptions, and mixed configurations of complete and partial gene copies, as a source of genotype-phenotype discrepancies from short-read data. We conduct further extended investigations to other antibiotic families and into another bacterial species: Escherichia coli. Methods We analyzed collections of E. faecium and E. coli genomes, integrating high-quality complete assemblies, simulated Illumina short reads, and matched AMR phenotypic data. The integrity, copy number, and allelic diversity of ARGs were examined for multiple antibiotic classes, and their impact on ARG detection and accuracy of AMR determination was assessed using several commonly used bioinformatic tools (SRST2, ARIBA and AMRFinderPlus). Results For E. faecium, after ruling out the effect of specific tet allelic variants on tetracycline susceptibility, we found that the integrity and copy number of tet(M) had a major effect on detection accuracy. Duplicated and incomplete ARGs are also common in E. faecium genomes, particularly for macrolides (erm(B)) and aminoglycosides (ant(6)-Ia and aph(3')-IIIa). In E. coli, similar patterns were observed for tet(A), erm(B) and aminoglycoside-associated genes (aph(3')-IIIa and ant(6)-Ia). Across ARGs in both species, short-read mapping methods wrongly reported interrupted genes as complete in some instances, while assembly-based methods often failed to resolve complete copies of duplicated genes. Detection accuracy improved when tools were adapted to account for gene integrity and when extended AMR databases incorporating species-specific alleles were included. Conclusions Our findings reveal that bioinformatic limitations in dealing with ARG copy number and completeness, and in accounting for allelic variation, underly a substantial source of genotype-phenotype errors, highlighting the need for improved AMR databases and bioinformatic tools that consider these factors to achieve reliable genomic prediction of AMR.

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24.
arXiv (CS.CV) 2026-06-19

SA-VIS: Sparse frame Annotations for training Video Instance Segmentation

作者:
Edoardo Mello Rella↗Ajad Chhatkuli↗Shipra Jain↗Ender Konukoglu↗Luc Van Gool↗

Recent online video instance segmentation (VIS) methods have achieved impressive results, thus becoming the preferred approach to segment instances in videos. Despite the resurgence of impressive single image models, the online (or semi-online) VIS approaches outperform single-image models (e.g., based on SAM) by using long sequences of densely annotated frames during training. However,such a training setup of VIS is expensive in the sense of compute as well as dense annotations required. In order to solve these major flaws, we argue that the effective modeling of the instances and their evolution in videos do not require densely annotated frames. To that end, we propose a simple and effective module, called Past-frames Feature Propagation (PFP) which aggregates low-dimensional features from the image encoder of multiple frames. This simple low-compute module provides tremendous learning capability in using sparse video frame labels for end-to-end training. Combined with a light-weight frame-specific Instance Queries, our Sparse frame Annotation VIS (SA-VIS) significantly improves performance over its baseline. Most interestingly, our simple design that avoids complexities effectively bridges the gap in accuracy between training on sparsely and densely annotated video sequences. This translates to a mere 0.4% drop in performance of SA-VIS when using annotations for only 1/5 of the images in the dataset. Empirically, SA-VIS shows strong improvements over the baseline on YouTube-VIS 2019/2021/2022 and Occluded VIS (OVIS) and an over 1% improvement in AP on the state-of-the-art in a limited annotations scenario.

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25.
medRxiv (Medicine) 2026-06-11

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

作者:
Uria-Regojo↗Fernandez-Caballero↗Lopez-Alcojor↗Lopez-Lopez↗Benitez↗Rodilla↗Avila Fernandez↗Trujillo-Tiebas↗M. J↗Osorio↗Corton↗Almoguera↗…

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.

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