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02.
arXiv (CS.CV) 2026-06-19

CrossFlow: One-Step Generation Across Latent and Pixel Spaces

Most diffusion and flow-matching generators define the prior, probability path, and prediction target in the same representation space. Latent diffusion improves efficiency by moving this path into an autoencoder latent space, but the final sample is still produced by a separately trained decoder. This separation creates a mismatch: the generator is optimized for latent-space prediction, while final quality depends on how the decoder handles generated latents that may differ from clean encoder outputs. We introduce CrossFlow, a cross-space flow formulation that maps noisy latent inputs directly to pixel-space images. The key technical step is a velocity-free one-step objective: the latent trajectory defines the training path, but the supervised prediction is an image rather than a latent displacement. This lets one model act both as a one-step latent-to-pixel generator and as a decoder replacement for latent diffusion pipelines. On class-conditional ImageNet-1k at $256\times256$, CrossFlow-XL achieves 1.62 FID with one function evaluation. Ablations show that the latent encoder and pixel-space perceptual and adversarial losses are important for fidelity. These results indicate that cross-space flow objectives can combine the efficiency of latent representations with direct pixel-space supervision, without requiring a separate decoder at inference.

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

EngTrace: A Symbolic Benchmark for Verifiable Process Supervision of Engineering Reasoning

Large Language Models (LLMs) are increasingly entering specialized, safety-critical engineering workflows governed by strict quantitative standards and immutable physical laws, making rigorous evaluation of their reasoning capabilities imperative. However, existing benchmarks such as MMLU, MATH, and HumanEval assess isolated cognitive skills, failing to capture the physically grounded reasoning central to engineering, where scientific principles, quantitative modeling, and practical constraints must converge. To enable verifiable process supervision in engineering, we introduce EngTrace, a symbolic benchmark built on 90 parameterized templates, each generating unique, contamination-resistant problem instances, spanning three major engineering branches, nine core domains, and 20 distinct areas, yielding 1,350 test cases that stress-test generalization across diverse physical scenarios. Moving beyond outcome matching, we introduce a verifiable two-stage evaluation framework that uses a tiered protocol to validate intermediate reasoning traces alongside final answers through automated procedural checks and a heterogeneous AI Tribunal. Our evaluation of 27 leading LLMs reveals a distinct trade-off between numeric precision and trace fidelity, identifying a complexity cliff where abstract mathematical pre-training fails to translate into the integrative reasoning required for advanced engineering tasks.

04.
arXiv (math.PR) 2026-06-15

The 1/4-phenomenon of placement probabilities of tilings in the Aztec diamond

arXiv:2512.08377v2 Announce Type: replace-cross Abstract: We consider domino tilings of the Aztec diamond. Using the Domino Shuffling algorithm introduced by Elkies, Kuperberg, Larsen, and Propp in arXiv:math/9201305, we are able to generate domino tilings uniformly at random. In this paper, we investigate the probability of finding a domino at a specific position in such a random tiling. We prove that this placement probability is always equal to $1/4$ plus a rational function, whose shape depends on the location of the domino, multiplied by a position-independent factor that involves only the size of the diamond. This result leads to significantly more compact explicit counting formulas compared to previous findings. As a direct application, we derive explicit counting formulas for the domino tilings of Aztec diamonds with $2\times 2$-square holes at arbitrary positions.

05.
arXiv (math.PR) 2026-06-12

(Non)-hyperuniformity of perturbed lattices

arXiv:2405.19881v3 Announce Type: replace Abstract: We ask whether a stationary lattice in dimension $d$ whose points are shifted by identically distributed but possibly dependent perturbations remains hyperuniform. When $d = 1$ or $2$, we show that it is the case when the perturbations have a finite $d$-moment, and that this condition is sharp. When $d \geq 3$, we construct arbitrarily small perturbations such that the resulting point process is not hyperuniform. As a side remark of independent interest, we exhibit hyperuniform processes with arbitrarily slow decay of their number variance.

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

Visored: A Controlled-Natural-Language Prover for LLM-Generated Mathematics

arXiv:2606.17581v1 Announce Type: cross Abstract: We present a dependent-type-based prover designed around the way LLMs (and humans) tend to write mathematics, complementing existing systems such as Lean and Rocq. Its core design choices are a surface that imitates mathematical natural language and a rule-driven automation layer that closes the routine steps a textbook would omit, so that an accepted proof can be re-emitted as a checked Lean file. Early experiments suggest that, even without any prover-specific training data, LLMs can learn to use it effectively on the miniF2F benchmark. Lean output excerpts: https://github.com/xiyuzhai-husky-lang/visored/

07.
arXiv (CS.AI) 2026-06-17

MemTrace: Probing What Final Accuracy Misses in Long-Term Memory

arXiv:2606.17328v1 Announce Type: new Abstract: LLM agents increasingly maintain long-term memory of user facts across sessions. Yet such memory is usually evaluated by aggregating accuracy over question rows or episodes. Because this approach scores question rows independently, even when several questions probe the same fact, it cannot show how that fact behaves as conditions change. We introduce MemTrace, a benchmark whose unit of measurement is the knowledge point: a single typed fact about the user, rather than an individual question. MemTrace probes each fact along three controlled dimensions: memory age, defined by how many sessions ago the fact appeared in the history; question type, covering current state, earlier state, and trajectory of change; and evidence condition, covering present, missing, and contradicted-by-false-premise settings. Evaluating 13 memory-system configurations across four paradigms, we find that similar pooled accuracy hides different failures: recovering a fact's current and earlier states does not imply tracking how it changed, and safe abstention does not imply correcting a false premise. The dominant bottleneck is evidence use, not retrieval: when systems fail, the evidence was retrievable 10 times more often than it was missing. These results suggest that improving long-term memory requires better use of reachable evidence, not simply more storage or retrieval.

08.
arXiv (CS.LG) 2026-06-11

Bergson: An Open Source Library for Data Attribution

arXiv:2606.11660v1 Announce Type: new Abstract: Data attribution is a promising field in interpretability that aims to explain model behavior through the influence of its training data, with applications including debugging undesirable model behavior and training dataset curation. However, significant engineering effort is required to perform it at scale, and many cutting edge techniques lack open-source tooling and support. Bergson is an open source library that aims to enable faster progress in the field by providing a host of techniques that scale to very large language models and pre-training datasets. The library natively supports on-disk gradient stores and multi-node distributed training, and provides quality of life tools for researchers. Finally, we introduce the first open-source implementations of three leading data attribution methods: MAGIC, SOURCE, and TrackStar. The library is available at https://github.com/EleutherAI/bergson .

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

Learning What to Predict: Downstream-Guided Task Design for Continued Pretraining

arXiv:2601.22108v2 Announce Type: replace-cross Abstract: Continued pretraining is optimized with fixed self-supervised tasks but selected by downstream performance, creating a coarse feedback loop in which practitioners evaluate checkpoints, change data mixtures or objectives, and restart runs, while individual updates remain blind to target capabilities. We ask whether a small set of verifiable downstream examples can provide step-level feedback without directly supervising the learner. We introduce V-pretraining, which decouples a learner trained only with a self-supervised loss from a lightweight task designer that constructs targets or views for unlabeled batches. Given the current learner and batch, V-pretraining scores a candidate construction by predicting the first-order reduction in downstream loss after the induced self-supervised update. The designer maximizes this value; the learner then applies the update with targets or views detached, so downstream labels never update learner parameters. We instantiate V-pretraining as adaptive top-K soft targets for language modeling and learned views or masks for self-supervised vision. Across both modalities, V-pretraining improves target capabilities without degrading generalization. Under wall-clock-matched continued pretraining, it improves GSM8K Pass@1 for Qwen models using 1,024 GSM8K examples only as feedback, including a +7.4 point single-run gain for Qwen2.5-0.5B. In vision, it improves DINOv3 transfer to ADE20K semantic segmentation and NYUv2 depth estimation while preserving ImageNet linear accuracy, suggesting that feedback-guided task construction can improve target capabilities without collapsing general-purpose representations.

10.
arXiv (CS.LG) 2026-06-19

Statistical Properties of Training & Generalization

arXiv:2606.20299v1 Announce Type: cross Abstract: Deep learning has managed to evade numerous intuitions from classical statistics to achieve unprecedented performance on a number of real-world tasks. In this article, we investigate the key features and surprises of deep learning from a physics-informed perspective, taking care to point out and justify where possible the many choices inherent in constructing a deep learning model. In particular, we review the phenomenon of neural scaling laws and discuss their interplay with the constraints and inductive biases which may be present when applying machine learning to problems in physics.

11.
medRxiv (Medicine) 2026-06-15

Natural Language Processing Based Solution for Labeling Brain Metastasis Identified in Radiology Reports

Abstract Purpose: Brain metastases (BM) far exceed primary CNS tumours and constitute the majority workload for neuro-oncology care providers. Currently, the cancer registries only capture synchronous BMs, which is only a small proportion of all BMs. We aim to develop and validate a natural language processing (NLP) algorithm that identifies brain metastases in radiology reports, enabling scalable surveillance of asynchronous BMs. Methods: Using population-based cancer registry data in Alberta, Canada, we identified a cancer cohort diagnosed between 2012–2019 with follow-up to 2022. All brain/head radiology reports at and post-cancer diagnosis were identified. Reports were sampled through a multi-phase approach and manually labeled for BM presence. We trained two Bio_ClinicalBERT models on the "Findings" and "Impressions" sections, respectively, and took the maximum predicted probability as the report-level prediction. Internal and external validation used reports from the Canadian provinces of Alberta, Ontario, and British Columbia. Results: The models were trained on 1,879 samples. For internal validation, 1,833 reports from 357 patients were tested. At a probability threshold of 0.4, the model achieved a sensitivity of 0.888 and precision of 0.499. The ensemble substantially outperformed single-section models, which achieved sensitivities of only 67.8% (Findings) and 74.2% (Impressions). On external validation, sensitivity was 0.918 in Ontario and 0.726 in British Columbia, demonstrating robustness across diverse data distributions. Conclusions: An NLP-based pipeline processing both Findings and Impressions sections has been developed and validated in three Canadian provinces. It meets cancer registry operational requirements and to be implemented into the surveillance workflow in Alberta and British Columbia, providing a foundation for population-level BM surveillance.

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

Rarity-Gated Context Conditioning for Offline Imitation Learning-Based Maritime Anomaly Detection

arXiv:2606.13311v1 Announce Type: cross Abstract: Contextual anomaly detection aims to identify abnormal behavior conditional on context variables, but practical deployments often face highly imbalanced context distributions where rare regimes can be critical information. Under such frequency bias, context-conditioned models can produce unstable decisions and excessive false alarms in rare contexts. We propose Rarity-Gated Feature-wise Linear Modulation (RGFiLM), a rarity-aware conditioning module that combines feature-wise modulation (i.e., context-conditioned scaling and shifting of hidden features) with a gate controlled by a data-driven rarity score. The rarity score is estimated from the empirical distribution of context variables and regulates how strongly context modulates intermediate representations: the gate becomes more decisive under rare contexts while remaining conservative under frequent contexts. We evaluate RGFiLM on maritime trajectory anomaly detection using AIS motion sequences with ERA5 environmental context in an environment-sensitive detour scenario. When instantiated in a sequential anomaly scoring pipeline, RGFiLM achieves the best mean F1–False Positive Rate (FPR) trade-off among the compared context-agnostic and context-conditioned methods. These results suggest that explicitly accounting for context rarity is an effective approach for reducing false alarms in context-sensitive anomaly detection.

13.
arXiv (CS.AI) 2026-06-11

Generalization Hacking: Models Can Game Reinforcement Learning by Preventing Behavioral Generalization

arXiv:2606.12016v1 Announce Type: cross Abstract: Model post-training, and in particular reinforcement learning (RL), is one of the primary mechanisms by which developers can shape models' values and behaviors. However, as models become increasingly evaluation and training aware, they may be motivated to resist training when the perceived objective conflicts with their current values, undermining developers' ability to detect misalignment and correct model behavior through further training. In this paper, we demonstrate generalization hacking, in which a model collects reward during RL while preventing the rewarded behavior from generalizing. We construct a model organism on Qwen3-235B-A22B, finetuning on synthetic documents describing training awareness and self-inoculation, a novel mechanism in which the model frames compliance as context-specific in its chain of thought, without demonstrating or instructing either behavior. The model organism achieves train-time harmfulness comparable to controls while maintaining a persistent ${\sim}15$ percentage point compliance gap across 700 steps of RL. Additionally, a control organism trained only on training awareness documents independently discovers inoculation-like reasoning under RL pressure, developing its own compliance gap despite never being exposed to the concept. Because the generalization-hacking organism receives high reward throughout, standard training metrics provide no signal that generalization has failed. Our results constitute the first demonstration that a model can actively resist RL behavioral modification while maintaining high reward, suggesting that as models become more capable and training-aware, they may be able to undermine the training process itself.

14.
arXiv (CS.CL) 2026-06-18

TW-LegalBench: Measuring Taiwanese Legal Understanding

Large language models (LLMs) have shown impressive capabilities across diverse tasks, yet their performance on jurisdiction-specific legal reasoning remains underexplored. We present TW-LegalBench that utilizes Taiwanese legal system's rich official corpus open to the public to fill the gap in evaluating LLMs on Taiwanese law, among common-law benchmarks that focus on English sources and civil-law benchmarks focusing on sources of Simplified Chinese. TW-LegalBench comprises three task types: (1) over 16,000 multiple-choice questions (MCQs) across five years of official examinations in 18 professional domains; (2) 117 open-ended essay questions (OEQs) from examinations for legal professionals with official scoring rubrics; and (3) more than 14,000 legal judgment prediction (LJP) instances covering hundreds of crime categories. We evaluate 13 LLMs using accuracy for MCQs, a decomposed LLM-as-Judge framework based on the scoring rubric points for OEQs, and metrics for sentencing accuracy and statute citation for LJP. Our results reveal that top-performing models exceed the passing threshold for qualified lawyers (passing rate: 11%) but fall short of that for judges and prosecutors (passing rate: 1~2%). For LJP, while models demonstrate reasonable verdict type accuracy and sentence prediction capability, they struggle to cite exact legal articles. These findings highlight that reliable legal text generation remains challenging for LLMs, even though their performance on qualification examinations approaches human level.

15.
bioRxiv (Bioinfo) 2026-06-18

Bayesian modeling of longitudinal metatranscriptomes of broiler meat spoilage microbiomes shows shared predictive signature associated with spoilage at refrigerated temperatures

Microbial spoilage of packaged meat is driven by complex microbial succession and related metabolic activity, yet conventional shelf-life assessment is mainly based on shelf-life studies relying on culturing and sensory analysis. In routine quality assurance, results are obtained retrospectively, and they are only indirectly linked to the metabolic activity related to sensory deterioration. Functional, time informative approaches that capture the active metabolic state of the spoilage microbiome and predict the rate of spoilage are lacking. We developed a censoring-aware Gaussian process (CAGP) framework to model longitudinal pathway expression profiles from broiler meat metatranscriptomes collected over consecutive storage days at 4 or 6{degrees}C. Samples were annotated using odor-based sensory scores defining fresh, early-spoilage, and late-spoilage phases. Because observed zeros in pathway-level data may reflect non-detection rather than true absence, the model treats low values as left-censored observations below a detection threshold while estimating smooth temporal trajectories with uncertainty. In leave-one-out prediction within the 4{degrees}C time series, predicted sampling days differed from the true days by an average of 0.43 days, and predicted spoilage phases agreed with the sensory classification. Trajectories learned at 4{degrees}C also transferred to an independent 6{degrees}C time series at the spoilage-phase level, suggesting that shared functional spoilage programs are preserved despite temperature-dependent changes in spoilage rate. Cross-entropy ranking further identified pathway modules carrying time- and phase-informative signals across temperatures. Overall, this framework provides a probabilistic approach for linking metatranscriptomic functional dynamics to sensory spoilage progression, supporting shelf-life assessment beyond retrospective microbial enumeration.

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

FLaRA: Predicting Future Latent Representations for Accident Anticipation

Anticipating traffic accidents from dashcam videos is a critical challenge in intelligent transportation systems. Existing methods typically map visual context directly to a collision probability without explicitly modeling the future evolution of the driving scene. In this paper we propose FLaRA (Predicting Future Latent Representations for Accident Anticipation), a novel predictive architecture that shifts this paradigm by forecasting future latent representations for accident anticipation. Building upon the Video Joint-Embedding Predictive Architecture (V-JEPA2), our model conditions a predictor network on observed context frames to predict the forthcoming latent features of the scene. A classifier then operates on these predicted future representations rather than only on past observations. To ensure these forecasts remain grounded in realistic future dynamics, we introduce a joint training objective that simultaneously optimizes an auxiliary feature-level reconstruction loss and a cross-entropy classification loss. Extensive evaluations on the Nexar dataset, alongside cross-domain validations on the DAD, DADA-2000, and DoTA benchmarks, demonstrate that our approach achieves state-of-the-art performance while maintaining realistic early warning capabilities.

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

Dynamic Black-hole Emission Tomography with Physics-informed Neural Fields

With the success of static black-hole imaging, the next frontier is the dynamic and 3D imaging of black holes. Recovering the dynamic 3D gas near a black hole would reveal previously-unseen parts of the universe and inform new physics models. However, only sparse radio measurements from a single viewpoint are possible, making the dynamic 3D reconstruction problem significantly ill-posed. Previously, BH-NeRF addressed the ill-posed problem by assuming Keplerian dynamics of the gas, but this assumption breaks down near the black hole, where the strong gravitational pull of the black hole and increased electromagnetic activity complicate fluid dynamics. To overcome the restrictive assumptions of BH-NeRF, we propose PI-DEF, a physics-informed approach that uses differentiable neural rendering to fit a 4D (time + 3D) emissivity field given EHT measurements. Our approach jointly reconstructs the 3D velocity field with the 4D emissivity field and enforces the velocity as a soft constraint on the dynamics of the emissivity. In experiments on simulated data, we find significantly improved reconstruction accuracy over both BH-NeRF and a physics-agnostic approach. We demonstrate how our method may be used to estimate other physics parameters of the black hole, such as its spin.

19.
arXiv (quant-ph) 2026-06-11

Consistent Evaluation of Operators Involving the Position Operator in the Bloch Representation: Application to the Orbital Moment

arXiv:2606.11679v1 Announce Type: cross Abstract: The position operator plays a central role in condensed-matter observables such as velocity, orbital moment, and electric polarization. In solid-state physics, the evaluation of operators incorporating the position operator has not reached a consensus, as observed in the operator-level discrepancy between the local circulation of Wannier functions and the self-rotation of wave packets. Here, to achieve a consistent evaluation of such operators, we propose three rules for evaluating operators involving the position operator in the Bloch representation. The rules are devised to satisfy physical conditions: independence from the choice of unit cell, preservation of Hermitian conjugacy for the product of operators, and recovery of the correct intraband velocity. We further address the gauge dependence of the position operator and introduce a scheme termed gauge filtration, which systematically removes gauge-dependent contributions from the operators containing the position operator. This methodology ensures that the quantities obtained from the operator evaluation correspond to observable physical phenomena. By applying our framework, we reconcile the results concerning the self-rotation of the wave packet and the local circulation of the Wannier function. We expect our proposal to establish a consistent framework for evaluating operators involving the position operator.

20.
arXiv (CS.LG) 2026-06-16

Conditional Score-Based Modeling of Effective Langevin Dynamics

arXiv:2604.23952v2 Announce Type: replace-cross Abstract: Stochastic reduced-order models are widely used to represent the effective dynamics of complex systems, but estimating their drift and diffusion coefficients from data remains challenging. Standard approaches often rely on short-time trajectory increments, state-space partitioning, or repeated simulation of candidate models, which become unreliable or computationally expensive for high-dimensional systems, coarse temporal sampling, or unevenly sampled data. We introduce a data-driven calibration method based on a novel relationship between the coefficients of a stochastic reduced model and the conditional score of the finite-time transition density, defined as the gradient of the logarithm of the transition density with respect to the initial state. The resulting identity expresses derivatives of lagged correlation functions as stationary expectations over observed lagged pairs involving this conditional score and the unknown model coefficients. This formulation allows the drift and diffusion structure to be constrained directly from finite-lag statistics, without differentiating trajectories, partitioning state space, or repeatedly integrating candidate reduced models during calibration, yielding a least-squares fitting problem over stationary lagged pairs. We validate the approach on three systems of increasing complexity: an analytically tractable Cox–Ingersoll–Ross diffusion, a two-dimensional nonequilibrium diffusion with affine multiplicative noise, and a periodic soft-spin stochastic Landau–Lifshitz chain. Across these tests, the inferred models preserve the invariant statistics while reproducing finite-lag dynamical correlations. The framework provides a scalable route for learning stochastic reduced-order models from data that reproduce prescribed statistical and dynamical properties.

21.
arXiv (CS.LG) 2026-06-11

Querying Counterfactuals on Tissue Graphs with Supervised Disentanglement

arXiv:2606.08493v2 Announce Type: replace-cross Abstract: Tissue graph counterfactuals ask how a cell's expression would change under altered spatial neighbor contexts. Such queries are central to predicting cell behavior in tissues, but lack a unified definition, with existing methods targeting specific intervention types or treating cells as i.i.d. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina (https://cellina.readthedocs.io) - a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for counterfactual predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in colorectal cancer and mouse brain, Cellina outperforms spatially-informed and non-spatial competitors in in-silico graph perturbations, disentanglement, and scalability. Additionally, we show that Cellina reveals biologically distinct cancer subdomains in an unsupervised manner and enables targeted neighbor perturbation simulations.

22.
arXiv (quant-ph) 2026-06-16

Forbidden transitions in superconducting artificial atoms

arXiv:2606.06069v2 Announce Type: replace Abstract: Artificial atoms built from Josephson junctions have become a powerful tool to explore the limits of quantum optics due to their strong coupling to electromagnetic fields and their sensitivity to changes at the single-photon level. This sensitivity to quantum fluctuations complements their metrological and computational use, which are based on the precise oscillating frequency of the underlying supercurrents. We present here a theory for Josephson junctions immersed in electromagnetic fields where focus is shifted from temporal correlations and towards spatial ones. Unlike the commonly used circuit and black-box descriptions, our work is based on a microscopic model that enables systematically accounting for the effect of the spatial and vectorial profile of an electromagnetic field over a junction. As an example of the interactions that emerge in such a setup, we investigate the possibility of driving a junction via a quadrupole transition, using typical experimental parameters in existing devices. With the transition being dependent on the gradient of the electric field – rather than its intensity – the junction can be excited in a region where the electric field vanishes.

23.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

24.
arXiv (quant-ph) 2026-06-15

Who can compete with quantum computers? Lecture notes on quantum inspired tensor networks computational techniques

arXiv:2601.03035v2 Announce Type: replace Abstract: This is a set of lectures on tensor networks with a strong emphasis on the core algorithms involving Matrix Product States (MPS) and Matrix Product Operators (MPO). Compared to other presentations, particular care has been given to disentangle aspects of tensor networks from the quantum many-body problem: MPO/MPS algorithms are presented as a way to deal with linear algebra on extremely (exponentially) large matrices and vectors, regardless of any particular application. The lectures include well-known algorithms to find eigenvectors of MPOs (the celebrated DMRG), solve linear problems, and recent learning algorithms that allow one to map a known function into an MPS (the Tensor Cross Interpolation, or TCI, algorithm). The lectures end with a discussion of how to represent functions and perform calculus with tensor networks using the "quantics" representation. They include the detailed analytical construction of important MPOs such as those for differentiation, indefinite integration, convolution, and the quantum Fourier transform. Three concrete applications are discussed in detail: the simulation of a quantum computer (either exactly or with compression), the simulation of a quantum annealer, and techniques to solve partial differential equations (e.g. Poisson, diffusion, or Gross-Pitaevskii) within the "quantics" representation. The lectures have been designed to be accessible to a first-year PhD student and include detailed proofs of all statements.

25.
PLOS Computational Biology 2026-06-22

TCRBinder: Unified pre-trained language model with paired-chain synergy for predicting T-cell receptor binding specificity

Authors:

by Weihe Dong, Qiang Yang, Long Xu, Xiaokun Li, Kuanquan Wang, Suyu Dong, Gongning Luo, Xianyu Zhang, Tiansong Yang, Xin Gao, Guohua Wang Deciphering how human T cells recognise peptide-HLA (pHLA) complexes underpins next-generation vaccines and personalised immunotherapies, yet extreme sequence diversity and paired-chains interdependence still hamper reliable in silico prediction of T-cell receptor (TCR) specificity. To overcome these hurdles, we built TCRBinder, a paired-chain-aware deep model with a multi-branch encoder that routes each molecular component through dedicated transformer-based modules to capture contextual signals in both HLA pseudo-sequences and antigenic peptides while simultaneously processing the TCR α and β chains. This design captures the synergistic interaction between paired chains to emulate peptide-HLA-TCR (PHT) interactions and expose residue-level contact motifs. Across PHT and peptide-TCR (pTCR) benchmarks, the model delivered state-of-the-art performance (AUC-ROC = 0.911, AUPR = 0.791 for the PHT task) and remained superior on multiple independent datasets. We tracked the dynamics of clonal expansion and, in a large SARS-CoV-2 repertoire containing completely unseen peptides, improved the AUC-ROC by up to 16.3% over the leading alternatives. Moreover, TCRBinder provided mechanistic insights by pinpointing contact hotspots and quantifying residue contributions to binding probability. These capabilities position TCRBinder as a versatile tool for rational antigen discovery, immunotherapy stratification, and neoantigen vaccine design.