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

Benchmarking Instance-Dependent Label Noise with Controlled Corruptions

arXiv:2606.14965v1 Announce Type: new Abstract: Synthetic instance-dependent label noise (IDN) benchmarks are widely used to evaluate noisy-label learning methods, yet existing approaches typically generate noise through imperfect annotators or classifier raters, leaving the source of ambiguity implicit. We introduce CILN, a benchmark generation framework that creates IDN through controlled input corruptions. A diverse voter pool labels corrupted instances, producing benchmark datasets in which both the source and severity of ambiguity are explicit and controllable. Using CIFAR10, MNIST, and Adult, we construct 90 benchmark settings spanning multiple corruption families and severity levels. Our experiments show that the resulting benchmarks exhibit genuine instance-dependent noise, provide diverse confusion structures, and, on CIFAR-10, can produce label distributions that are closer to human uncertainty than an existing synthetic IDN benchmark. We further demonstrate that corruption-mediated IDN can expose failure modes of popular noisy-label learning methods, including Co-Teaching and DivideMix, that are not observed under comparable levels of rater-fallibility noise. These findings suggest that noise structure, not only noise rate, plays an important role in benchmark difficulty and algorithm behavior. By making ambiguity generation explicit and controllable, CILN provides a complementary benchmarking framework for studying noisy-label learning under diverse sources of instance difficulty.

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

Schattor: Schatten-family methods for deep learning optimization

arXiv:2606.15702v1 Announce Type: cross Abstract: Modern deep learning optimization features heterogeneous parameter structures, noisy gradients, and highly nonconvex landscapes, posing significant challenges for both algorithm design and theoretical analysis. Motivated by the limitations of SGD and the success of adaptive optimizers, we propose {\it Schattor}, a family of adaptive first-order methods based on Schatten norms. Schattor unifies SGD and the recently proposed matrix-variate adaptive optimizer Muon within a single Schatten-norm-based framework. We establish dimension-free stationarity guarantees for methods in the Schattor family for stochastic matrix optimization problems via a novel matrix martingale moment bound. We also develop multi-block extensions that adaptively balance block-wise optimization progress and prove dimension-free stationarity guarantees in this more general setting.

03.
arXiv (CS.CL) 2026-06-16

Risk-Aware LLM Agents for Geospatial Data Retrieval: Design and Preliminary Adversarial Evaluation

We present an LLM-driven framework for retrieving remote sensing data from cloud-based geospatial catalogues using natural language queries. The system converts user intent into structured API calls, enabling efficient access to satellite imagery and environmental datasets. The architecture integrates three agents: Guardrail for safety and policy enforcement, General-QA for intent interpretation, and Recommender-Analyst for schema-aware API call generation. This coordinated design ensures reliable, semantically aligned interaction with external data services. The modular framework is portable across platforms through API schema substitution and supports applications in environmental monitoring, disaster response, and climate analysis. It establishes a scalable interface between user intent and geospatial infrastructure, enabling streamlined and automated Earth observation workflows. Preliminary experiments under adversarial multi-turn settings show that prompt-level safety instructions improve robustness, although rare high-impact failures persist in API manipulation scenarios and highlight the need for adaptive, system-level defenses that balance safety, usability, and cost efficiency, which motivates the use of our intercept-level Guardrail agent.

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

Towards More General Control of Diffusion Models Using Jeffrey Guidance

A key strength of diffusion models lies in their flexibility, since their outputs can be controlled at sampling time through guidance. However, beyond simple cases such as conditional sampling, the target distribution is often left implicit, defined only through a sampling rule or a heuristic energy function. To address this, we propose Jeffrey guidance, a principled framework that extends diffusion-model control to applications beyond what standard guidance can express. It leverages Jeffrey's rule of conditioning to update marginal distributions towards a prescribed target, preserving the conditional structure and minimally perturbing the joint distribution. We first demonstrate Jeffrey guidance by targeting a prescribed embedding distribution. With Inception embeddings as the target, this leads to substantial reductions in FID on both CIFAR-10 and FFHQ. We further apply Jeffrey guidance to fairness on CelebA-HQ, updating an unconditional diffusion model to enforce independence between attributes.

05.
arXiv (CS.AI) 2026-06-15

Numbers Already Carry Their Own Embeddings

arXiv:2606.14108v1 Announce Type: cross Abstract: We introduce Adelic operation-preserved embeddings (AOE), a training-free representation that captures both a number's real value and its modular (p-adic) signatures. This construction preserves additive and multiplicative structure by design, turning numerical input into embeddings that "speak in the language of mathematics." Unlike prior approaches that rely on task-specific retraining, AOE is plug-and-play and drops seamlessly into existing architectures. On algebraic combinatorics benchmarks, it delivers consistent gains including the first-ever perfect accuracy on the Weaving Pattern task-while suggesting a principled path forward for overcoming the long-standing "number problem" in AI.

06.
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.

07.
arXiv (quant-ph) 2026-06-17

Engineering entanglement and transport in interacting quantum walks with tailored potentials

arXiv:2606.17825v1 Announce Type: new Abstract: Controlling the interplay between particle propagation and quantum correlation generation is a central challenge in quantum transport. Here, we investigate two distinguishable continuous-time quantum walkers evolving on parallel one-dimensional lattices, interacting via distance-dependent potentials. While on-site interactions reproduce the typical bosonic behaviour, extending the interaction to a linear potential over multiple neighbors introduces controlled Bloch-like oscillations and shifts the bound-pair regime to stronger couplings. More generally, we explore a Coulomb-like interaction parameterized by strength, spatial scaling, and decay rate. This reveals a rich phase diagram including four distinct dynamical regimes: (i) a high-entropy, oscillatory regime akin to a linear potential; (ii) a strongly localized, bound-pair regime; (iii) a novel intermediate regime combining near-ballistic spreading with strong correlations; and (iv) a weakly interacting, free-propagation regime. Notably, regime (iii) achieves concurrent optimization of transport efficiency and entanglement, offering a sweet spot for correlated quantum dynamics. Our results provide a tool for designing interaction-engineered quantum walks with potential applications in quantum information processing and simulations.

08.
arXiv (CS.CV) 2026-06-16

Trusted Multi-View Deep Learning Classification of Fetal Congenital Heart Disease with Feature-level and Decision-level Fusion

Congenital heart disease (CHD) refers to the abnormal anatomical structure caused by the abnormal development of the heart and great vessels during embryonic development. Traditional diagnostics often fail to achieve high accuracy and efficiency, especially given the complexity of cardiac anatomy. This study presents a specialized multi-view deep learning framework for CHD binary classification using echocardiographic images. A large-scale CHD dataset, including five views, was used to train the model, enabling it to integrate multi-angle image data. The framework utilizes advanced feature extraction and attention mechanisms to improve diagnostic precision and reliability. An uncertainty-based decision-making component is also integrated to handle low-quality images, enhancing diagnostic outcomes. Experimental results show that this method achieves top-tier performance on our dataset and provides a robust tool for early CHD detection, underscoring its potential for clinical use. The dataset and source code will be released upon paper acceptance.

09.
arXiv (CS.CL) 2026-06-17

Do We Still Need Humans in the Loop? Comparing Human and LLM Annotation in Active Learning for Hostility Detection

Instruction-tuned LLMs can annotate thousands of instances at low cost. This raises two questions for active learning (AL): can LLM labels replace human labels within the AL loop, and does AL remain necessary when entire corpora can be cheaply labeled? We investigate both on a new dataset of 277,902 German political TikTok comments (25,974 LLM-labeled, 5,000 human-annotated), comparing LLM and human annotation across seven conditions, four encoders, and 10 random seeds. Under a two-question interface that mirrors the human annotation task, LLM annotation at scale outperforms human-supervised classifiers at roughly one-tenth the cost (\$28 for GPT-5.2 Batch API vs. \$316 for Prolific). The advantage holds for both a closed-source (GPT-5.2) and an open-weight (Qwen3.5-122B-10B) LLM, is robust under soft-label evaluation, and is unlocked specifically by the two-question decomposition; a holistic single-prompt baseline only ties with human supervision. AL provides no reliable advantage over random sampling under either LLM annotator. However, error structure varies sharply: only GPT-5.2 under the two-question interface produces classifiers with near-human FP/FN balance, while other LLM variants over-flag border-control and economic competition discourse. We release the dataset and code.

10.
arXiv (CS.LG) 2026-06-16

Representation Costs in Data Science: Foundations and the Quasi-Banach Spaces of Deep Neural Networks

arXiv:2606.14954v1 Announce Type: cross Abstract: We develop a general framework for analyzing representation costs of parametric data-fitting methods through their parameter-space regularizers. From this abstract perspective, we define representation costs for arbitrary parametric models and reveal their induced (native) function spaces. This unifies recent function-space views of data-fitting methods. We also prove that many natural results hold in this abstract setting, including representer theorems for parametric methods on their native spaces. The framework also rigorously connects parametric methods with their equivalent nonparametric descriptions under sufficient overparameterization. Classical methods and their native spaces, such as kernel methods / reproducing kernel Hilbert spaces, wavelets / Besov spaces, and shallow neural networks / variation spaces emerge as special cases of our abstract framework. A byproduct of "axiomatizing" the study of representation costs is that we also immediately obtain new results for deep neural networks: For depth-$L$ feedforward ReLU networks, their induced native spaces are $p$-normable quasi-Banach spaces with $p = 2/L$. This reveals that the inductive bias of deep neural networks (as given by the representation cost) cannot be captured by norms for depths $L > 2$.

11.
arXiv (CS.CV) 2026-06-18

Rethinking the Pointer Loss in Table Structure Recognition: Geometry-Aware Pointer Loss for Spatial Locality

Table Structure Recognition (TSR) using a pointer network achieves impressive results by predicting HTML sequences while aligning tags to detected text (or cell) regions. However, our analysis reveals that when pointer networks fail, 79.6% of errors occur between spatially adjacent cells (Manhattan distance

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

Language-Guided Abstraction for Visual Reasoning

The Abstraction and Reasoning Corpus (ARC) is viewed as a critical avenue to Artificial General Intelligence (AGI), as it enables models to learn abstract transformation rules from few-shot examples and then generalize to new tasks. However, prevalent ARC methodology is either pure language or vision-only (i.e., VARC). The former depends heavily on LLMs, consuming billions of parameters. The latter often struggles to capture high-level semantics, leading to overfitting on pixel-level patterns. To bridge this gap, we propose L-VARC, a novel framework that enhances visual reasoning via a language-guided Learning Using Privileged Information (LUPI) branch. Specifically, we design a Semantic Compression Module by feeding a unified, task-agnostic prompt into DeepSeek-V3. In this way, the raw LARC (a crowd-sourced language description dataset) can be substantially refined and structured, fitting with the context length constraint of standard text encoders (e.g., CLIP). Moreover, we design a Cross-Attention Projector to align visual features with semantic embeddings, aiming to guide the training of the ARC model. Notably, the LUPI branch is taken in the training process and will be discarded during inference, thereby yielding a lightweight model with a mere 18 million parameters. Extensive experiments demonstrate that our L-VARC effectively leverages linguistic priors to boost visual reasoning and outperforms state-of-the-art. Ablation studies further confirm the contribution of the two new designs towards the L-VARC framework. The code is available at https://github.com/GZHU-DVL/L-VARC.

13.
arXiv (CS.AI) 2026-06-12

Foresight: Iterative Reasoning About Clues that Matter for Navigation

arXiv:2606.12550v1 Announce Type: cross Abstract: Open-world mapless navigation from sparse language instructions requires resolving underspecified goals and inferring which environmental cues are relevant for reaching the goal. For instance, reaching an out-of-view destination may require interpreting ramps, signs, or detours that reveal where to go or which route to take. Prior works are limited by their reliance on known navigation factors and closed-set factor categories, or identify cues before motion planning and miss plan-dependent cues. We argue that pretrained Vision-Language Models (VLMs) can discover novel instruction-relevant cues, but require adaptation to focus on which cues matter and how they should influence motion planning. We realize these ideas in Foresight, a test-time framework in which a finetuned VLM alternates between proposing image-space motion plans and critiquing them using the language goal and visual context. Subsequent plans are conditioned on prior critiques, enabling iterative motion refinement before execution. To align plan critiques and refinements with open-set behavior preferences, we learn a reward model from human feedback and use it to post-train the VLM with reinforcement learning in the plan-critique loop. In offline evaluations and 6 real-world environments, Foresight improves average task success by 37% and reduces interventions per mission by 52% relative to state-of-the-art test-time reasoning and foundation-model baselines, while running in real-time on a Jetson AGX Orin. We will release code, data, and training details to support future work on test-time reasoning for robot motion refinement. Additional videos at: https://amrl.cs.utexas.edu/foresight

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

PSCT-Net: Geometry-Aware Pediatric Skull CT Reconstruction via Differentiable Back-Projection and Attention-Guided Refinement

arXiv:2606.19867v1 Announce Type: cross Abstract: Computed Tomography (CT) is essential for diagnosing pediatric craniofacial abnormalities, yet poses radiation risks to developing anatomies. Reconstructing 3D CT from sparse bi-planar X-rays offers a low-dose alternative but is severely ill-posed. Existing methods employ geometry-agnostic feature lifting, naively projecting 2D features into 3D without explicit spatial modeling, causing depth ambiguity and degraded osseous boundaries. We present PSCT-Net, a geometry-aware framework with differentiable back-projection. Differentiable back-projection establishes a spatially faithful volumetric prior, alleviating depth ambiguity. An Attention-Guided Projection (AGP-3D) module then learns non-linear voxel-wise correspondences between 2D regions and 3D locations. A Bidirectional Mamba (BiM-3D) module captures long-range volumetric dependencies with linear complexity. We further curate a private institutional pediatric skull CT cohort, PedSkull-CT, comprising normal and pathological cases for internal evaluation, addressing the gap in adult-centric, trunk-focused datasets.

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

On the Role of Computation in Reinforcement Learning

arXiv:2602.05999v3 Announce Type: replace Abstract: How does the amount of compute available to a reinforcement learning (RL) policy affect its learning? Can policies using a fixed amount of parameters, still benefit from additional compute? The standard RL framework does not provide a language to answer these questions formally. Empirically, deep RL policies are often parameterized as neural networks with static architectures, conflating the amount of compute and the number of parameters. In this paper, we formalize compute bounded policies and prove that policies which use more compute can solve problems and generalize to longer-horizon tasks that are outside the scope of policies with less compute. Building on prior work in algorithmic learning and model-free planning, we propose a minimal architecture that can use a variable amount of compute. Our experiments complement our theory. On a set 31 different tasks spanning online and offline RL, we show that $(1)$ this architecture achieves stronger performance simply by using more compute, and $(2)$ stronger generalization on longer-horizon test tasks compared to standard feedforward networks or deep residual network using up to 5 times more parameters.

17.
arXiv (quant-ph) 2026-06-11

Energy-Modulated Time-Asymmetric Spontaneous Collapse: Forward-Backward Dynamics from Stochastic Ito Reversal and Bright Solitons

arXiv:2606.06452v3 Announce Type: replace Abstract: We present a rigorous theoretical framework for symmetry breaking and quantum irreversibility arising from stochastic Ito field reversal within a cubic-quintic nonlinear Schrodinger equation (CQ-NLSE) formalism. Starting from three physically motivated considerations, forward and backward nonlinear stochastic differential equations are derived via the Ito calculus. Kinematic time-reversal is shown to be fundamentally incompatible with the Ito stochastic structure, yielding the universal asymmetry-coupling parameter of 2/3. An energy-driven collapse operator proportional to the product of noise strength, local probability density, and excitation energy squared is introduced, amplifying the collapse in high-density, high-excitation regions. Exactly bright soliton solutions are obtained for a quasi-one-dimensional BEC of attractive Li-7 atoms, with forward and backward amplitude ratio of 1.870. Heat map analysis of the parameter planes reveals that the forward collapse operator grows monotonically in time while the backward counterpart decays, achieving a ratio approximately 1030, sharply distinguishing this framework from conventional symmetric collapse models.

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

HarnessBridge: Learnable Bidirectional Controller for LLM Agent Harness

arXiv:2606.12882v1 Announce Type: new Abstract: Large language models are increasingly deployed as agents for long-horizon tasks, yet their performance is shaped not only by model capability and environment design, but also by the harness that mediates agent–environment interaction. Existing harnesses are largely manually engineered, making them difficult to scale as trajectories grow longer and interactions become more complex. In this work, we ask whether harness can be generated by a learnable plug-in module that can be trained in an end-to-end fashion. We introduce HarnessBridge, a lightweight learnable harness controller that parameterizes the agent–environment interface as a bidirectional projection. HarnessBridge learns two bidirectional projections: observation projection, which distills raw trajectories into compact, decision-relevant states, and action projection, which converts proposed actions into executable transitions or trajectory-grounded rejections. We train HarnessBridge on a harness supervision dataset via unified instruction tuning. On Terminal-Bench~2.0 and SWE-bench Verified, HarnessBridge matches or surpasses strong specialized harnesses while substantially reducing token usage and trajectory length, and generalizes from smaller generators to larger commercial models.

19.
medRxiv (Medicine) 2026-06-22

Assessment of adaptive functioning in Angelman syndrome using the Vineland Adaptive Behavior Scales, Third Edition

Purpose: This study examined longitudinal trajectories of adaptive functioning in 331 individuals with Angelman syndrome (AS) using the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) and examined differences by molecular subtype. Methods: A total of 331 individuals (156 females, 47%) with genetically confirmed AS (ages 6 months to 52 years) were assessed between 2018 and 2025, including 207 with a deletion subtype, 63 with uniparental disomy or imprinting defect, and 61 with a UBE3A point mutation. Growth scale values were analyzed using linear mixed-effects models with log2-transformed age. Results: Individuals with deletion subtypes demonstrated significantly lower adaptive functioning across domains compared to those with non-deletion subtypes. Adaptive skills across all Vineland-3 subdomains increased nonlinearly with age, showing faster growth early in life that slowed over time, with largely parallel trajectories across subtypes. Conclusion: Individuals with AS demonstrate slow but steady growth in adaptive functioning that continues into adulthood, with progress varying by molecular subtype. These findings provide updated natural history benchmarks and demonstrate the utility of the Vineland-3 for clinical trials.

20.
medRxiv (Medicine) 2026-06-23

Multidimensional motivation in aging: a person-centred framework spanning goal-directed behaviour, social reward and pleasure

Motivational changes are determinants of healthy aging, social engagement, and functional independence, and may signal early neurodegenerative risk. Existing assessment approaches in aging typically treat motivation as a unitary construct. Here, we introduce MotDem, an age-appropriate measure of motivation co-designed with people living with dementia, carers, and clinicians. Across a broad adult lifespan sample (18-80 years), MotDem revealed a robust three-domain motivational architecture encompassing goal-directed behaviour, social reward, and pleasure, with a fourth satiety factor retained as exploratory. This structure was replicated in an independent older cohort (45-80 years) from a different national context. MotDem showed strong convergence with established measures of apathy and anhedonia, alongside more modest associations with depressive symptomatology. Together, these findings show that motivational aging is multifaceted and poorly captured by traditional unitary assessment. MotDem provides a multidimensional framework for measuring distinct motivational drivers of heterogeneous aging trajectories, with implications for resilience, wellbeing, and neurodegenerative risk.

21.
arXiv (CS.CV) 2026-06-16

Uncertainty Quality of VGGT: An Analysis on the DTU Benchmark Dataset

Visual Geometry Grounded Transformer (VGGT) has already attracted a great deal of attention in a short period of time, not least due to the Best Paper Award at CVPR-2025. Similar to DUSt3R and MASt3R, VGGT aims to bring about a paradigm shift by replacing established methods like bundle adjustment and feature matching with a simple, unified, feed-forward neural network that predicts camera poses, depth maps, and dense 3D structure directly from multiple images of a scene in a few seconds. A key aspect is its ability to process an arbitrary number of views consistently in a single forward pass without any post-processing or iterative optimization. For photogrammetry, this opens new possibilities for real-time, scalable, and accessible 3D reconstruction. In this context, not only high reconstruction accuracy but also high-quality uncertainty estimates are crucial, as they foster trust and enable robust quality assurance. This paper therefore investigates the quality of VGGT's uncertainty predictions. The analysis identifies an effective confidence threshold for filtering VGGT's raw output and demonstrates that enhancing uncertainty quality holds strong potential for improving the accuracy of its 3D reconstructions.

22.
arXiv (CS.CV) 2026-06-17

DiFlow-TTS: Compact and Low-Latency Zero-Shot Text-to-Speech with Discrete Flow Matching

Zero-shot text-to-speech (TTS) has made significant progress in replicating unseen voices, yet balancing generation quality and inference efficiency remains challenging. Autoregressive models suffer from high latency, while diffusion-based approaches are constrained by training-time configurations. Moreover, most flow-based methods operate in continuous space, which introduces optimization challenges because continuous token spaces are inherently more complex than discrete ones. To address these limitations, we propose DiFlow-TTS, a novel zero-shot TTS framework based on discrete flow matching. The model consists of a deterministic Phoneme-Content Mapper for linguistic modeling and a Factorized Discrete Flow Denoiser that simultaneously generates prosody and acoustic token streams. Experimental results demonstrate the effectiveness of our approach across multiple evaluation metrics.

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

Training and Evaluating Diffusion Policies with Long Context Lengths

arXiv:2606.16447v1 Announce Type: cross Abstract: Imitation learning has enabled highly-dexterous robotic manipulation from RGB observations. Policies trained with these methods, however, typically condition robot actions on only a short history of observations. These policies cannot solve tasks that require memory and can get stuck repeatedly executing the same failing motions. In this work, we first benchmark policy performance as context length is incrementally increased from short to long, across a spectrum of tasks with varying local stability and memory requirements, and in multiple data regimes. To our knowledge, this is the first study to investigate context length in imitation learning at this level of detail. Our results challenge prior claims: naively scaling context length is not as brittle as advertised in literature. With an appropriate conditioning method and denoising backbone (UNet+Cross-Attention), single-task policies achieve high success rates on many tasks in the usual data regime even with naive scaling. Next, we propose a training algorithm to jointly train policies at multiple context lengths, further reducing the sample complexity of long-context learning. Finally, we apply our findings to re-evaluate some previously proposed solutions to long-context imitation learning.

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

No One-Size-Fits-All Neurons: Task-based Neurons for Artificial Neural Networks

arXiv:2405.02369v2 Announce Type: replace-cross Abstract: In the past decade, many successful networks are on novel architectures, which almost exclusively use the same type of neurons. Recently, more and more deep learning studies have been inspired by the idea of NeuroAI and the neuronal diversity observed in human brains, leading to the proposal of novel artificial neuron designs. Designing well-performing neurons represents a new dimension relative to designing well-performing neural architectures. Biologically, the brain does not rely on a single type of neuron that universally functions in all aspects. Instead, in our brain, neurons are often task-based. In this study, we address the following question: since the human brain is a task-based neuron user, can the artificial network design go from the task-based architecture design to the task-based neuron design? Since methodologically there are no one-size-fits-all neurons, given the same structure, task-based neurons can enhance the feature representation ability relative to the existing universal neurons due to the intrinsic inductive bias for the task. Specifically, we propose a two-step framework for prototyping task-based neurons. As the initial step, we evaluate the proposed framework using polynomials as base functions. Empirically, systematic experimental results on synthetic data, classic benchmarks, and real-world applications show that the proposed task-based neuron design is not only feasible but also delivers competitive performance over other state-of-the-art models.

25.
bioRxiv (Bioinfo) 2026-06-11

Viability of engineered AAVs via protein language models

Capsid engineering has greatly improved the performance of recombinant AAV vectors used for gene therapy. One commonly used strategy is the insertion of a short, 7-mer, peptide into surface-exposed loops to modify receptor interactions and enhance cell entry. While effective in receptor retargeting and improved transduction, these insertions might destabilize the capsid protein, hinder assembly, and thus limit production. While previous attempts have used deep mutational scanning and AI to predict which insertions are viable, there is lack in understanding the structural consequences of these peptide insertions at the amino-acid level. Here we combined experiments, deep sequencing and large protein language models to gain insight on the impact of 7-mer insertions on the VR-VIII region. We first characterize the biochemical properties of viable insertions, thus identifying which residues are well tolerated, and which should instead be avoided. We then focus on the nearby context of those insertions, by studying the effect of the linkers, either for highly diverse libraries or for individual variants known for their efficiency. Next, we study the broader context, by extending our analysis to the whole capsid sequence, and identifying regions that can tolerate insertions without long-ranged structural deformations that could affect capsid functionality. We conclude with a cross-serotype comparison and a viability analysis of tens of previously engineered variants. Our work showcases how AI can uncover structure-function rules governing the success of engineered AAV capsids.