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01.
arXiv (CS.CV) 2026-06-11

From Nominal Intensity to Equivalent Rainfall: A Path-Based Credibility Evaluation Framework for Simulated Rainfall in Autonomous-Driving Perception Tests

Authors:
Tian Xia↗Xin Zhao↗Shaolingfeng Ye↗Junyi Chen↗

Credible simulated-rainfall conditions are essential for identifying perception-system boundaries and supporting SOTIF-oriented risk assessment in automated driving. However, closed-field tests are often described only by nominal rainfall intensity or single-point measurements, making it difficult to align simulated rain fields with real rainfall and map test results to real-world scenarios. This paper proposes a path-based credibility evaluation method for simulated rainfall in autonomous-driving perception tests. Using the drop size and velocity joint distribution of real rainfall as the reference, each candidate path is represented by path-equivalent rainfall intensity, an uncertainty band, and a path-averaged Realism of Raindrop Distribution (RRD) score. Lidar target point-cloud count and mean reflectivity are further used for perception-consistency correction, quantifying the proxy capability of each simulated-rainfall path for real-rainfall perception effects. Experiments are conducted using about 10,000 real-rainfall raindrop-spectrum samples, 728 RainSense perception samples, and 45 spatial sampling points in a 2.4 m x 7.2 m simulated-rainfall area. Results show that spatial non-uniformity remains under the same nominal condition, confirming the need for path-based evaluation. The method identifies Path IV and Path VI as preferable candidates, with results of 11.54 +/- 0.31 mm/h, RRD = 0.43, and 8.28 +/- 0.34 mm/h, RRD = 0.46, respectively. These paths show more balanced performance in rainfall-intensity stability, raindrop-spectrum realism, and perception consistency. The proposed method supports path selection, condition description, and credible interpretation of autonomous-driving perception tests under rainfall.

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

Provable Recovery of Locally Important Signed Features and Interactions from Random Forest

Authors:
Kata Vuk↗Nicolas Alexander Ihlo↗Merle Behr↗

arXiv:2512.11081v2 Announce Type: replace-cross Abstract: Feature and Interaction Importance (FII) methods are essential in supervised learning for assessing the relevance of input variables and their interactions in complex prediction models. In many domains, such as personalized medicine, local interpretations for individual predictions are often required, rather than global scores summarizing overall feature importance. Random Forests (RFs) are widely used in these settings, and existing interpretability methods typically exploit tree structures and split statistics to provide model-specific insights. However, theoretical understanding of local FII methods for RF remains limited, making it unclear how to interpret high importance scores for individual predictions. We propose a novel, local, model-specific FII method that identifies frequent co-occurrences of features along decision paths, combining global patterns with those observed on paths specific to a given test point. We prove that our method consistently recovers the true local signal features and their interactions under a Locally Spike Sparse (LSS) model and also identifies whether large or small feature values drive a prediction. We illustrate the usefulness of our method and theoretical results through simulation studies and a real-world data example.

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03.
arXiv (CS.CV) 2026-06-18

Experimental Analysis of Neural Network-Based Image Classification on the CIFAR-10 Dataset

Authors:
Necati Kagan Erkek↗Emre Balci↗Berkin Halay↗

An experimental investigation of neural image classification on the CIFAR-10 benchmark is presented through fully connected and convolutional network formulations. The analysis emphasizes the complete learning pipeline: image vectorization, normalization, one-hot class encoding, supervised loss minimization, learning-rate selection, mini-batch training, convolutional feature extraction, max-pooling, and validation-based generalization assessment. A convolutional architecture with six convolutional layers and three max-pooling stages is evaluated for ten training epochs using a batch size of 128 and an Adam optimizer with a learning rate of 0.001. The validation accuracy reaches approximately 74.77%, while the validation loss begins to increase after the middle of training despite continued reduction in training loss. The resulting behavior illustrates the practical difference between representation learning and memorization, and it provides a compact experimental baseline for future studies on regularization, data augmentation, deeper architectures, and reproducible image-classification education.

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04.
bioRxiv (Bioinfo) 2026-06-16

Phylogenetic tree inference using generative models

Authors:
Dotan↗Schers↗Wygoda↗Pupko↗Belinkov↗

Accurate inference of phylogenetic trees is fundamental to evolutionary biology, yet existing methods rely on complex pipelines involving multiple sequence alignment, explicit evolutionary models, and computationally intensive tree search procedures. Here, we present BetaInfer, a generative framework that reformulates phylogenetic tree inference as a sequence transduction problem. BetaInfer leverages hybrid transformer-based architectures to directly map sets of unaligned sequences to phylogenetic trees represented in Newick format. Trained on large-scale simulated evolutionary data with known ground truth, BetaInfer learns to capture complex evolutionary signals directly from sequence data. Ensemble-based generation of multiple candidate trees further improves robustness, reducing reconstruction error by over 30% relative to single predictions. Across extensive evaluations on both simulated and empirical datasets, BetaInfer achieves competitive performance relative to state-of-the-art phylogenetic pipelines, matching, and in some cases exceeding, the accuracy of established likelihood-based and distance-based methods under a wide range of conditions. Interpretability analyses reveal that BetaInfer leverages internal pairwise-distance computations to synthesize evolutionary relationships into an integrated, global representation that supports direct tree generation. Together, these results demonstrate that generative models can serve as a viable and scalable alternative to standard phylogenetic pipelines.

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05.
arXiv (CS.AI) 2026-06-17

Quantifying Consistency in LLM Logical Reasoning via Structural Uncertainty

Authors:
Baishali Chaudhury↗Mengdie Flora Wang↗Hyunji Hayley Park↗Rahul Ghosh↗Sungmin Hong↗Jae Oh Woo↗

arXiv:2606.17312v1 Announce Type: new Abstract: Large language models can arrive at the same answer through reasoning paths that are unstable, contradictory, or difficult to rank consistently – a failure mode especially prevalent in multi-step deductive reasoning. Existing methods assess reliability primarily through output dispersion – measuring how much sampled answers differ – but this discards a complementary signal: whether the model can consistently rank competing reasoning candidates. We propose structural uncertainty, a consistency-aware framework derived from the stability of self-preference-induced rankings over sampled reasoning solutions. Given a query, we generate multiple candidate solutions and ask the model to judge pairwise preferences among its own outputs. We aggregate self-preferences into ranking distributions via Bradley-Terry modeling with PageRank, and decompose the signal into two entropy-based components: across-trial ranking instability and within-trial candidate ambiguity. Across five LLMs and eight benchmarks, structural signals provide information complementary to answer dispersion: on logical and mathematical reasoning tasks, the combination improves identification of unreliable instances, while on factual retrieval the structural signal collapses toward uniformity, diagnosing a regime boundary where reasoning-level consistency evaluation is uninformative. The two components relate differently to accuracy: within-trial ambiguity correlates positively with correctness – consistent with settings where multiple plausible solution paths remain competitive – while across-trial instability correlates negatively, signaling unreliable reasoning. Structural uncertainty is best understood not as a universal confidence estimator, but as a regime-sensitive evaluator of logical reasoning consistency.

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

Damage-TriageFormer: A Foundation-Model Framework for Typology-Based Building Damage Assessment from Mono-Temporal Imagery

Authors:
Yiming Xiao↗Yu-Hsuan Ho↗Sanjay Thasma↗Junwei Ma↗Ali Mostafavi↗

Decision-relevant building damage assessment is critical for prioritizing resources and recovery after a disaster, yet most automated methods either flatten damage into a single severity scale (no damage, minor, major, destroyed) or require paired pre- and post-event imagery that is often unavailable for emerging hazards. This paper presents Damage-TriageFormer, a single-image, post-event, footprint-conditioned model that produces a damage typology rather than a severity scale. We contribute: (1) DamageTriage-Bench, a new benchmark built from NOAA Emergency Response Imagery across Hurricane Michael (2018), Hurricane Helene (2024), and the 2025 Los Angeles wildfire complex, with five typology classes that distinguish roof damage from structural damage and, within each, partial from total extent; and (2) Damage-TriageFormer, which extends a DINOv3 ViT-L backbone with a Simple Feature Pyramid for higher-resolution instance pooling, a two-stage gated damage head, and an auxiliary severity-regression objective. Our model achieves macro F1 of 0.624 on validation and 0.619 on a held-out stratified test set, performing strongest where operational triage needs it most, with per-class F1 of 0.91 and 0.84 on undamaged buildings and total structural collapse, respectively. While the rare Total Roof Damage class remains difficult due to its limited examples and an inherently ambiguous label boundary, our results show that single-image post-event imagery can support actionable building damage typing, enabling targeted emergency response and resource allocation without a pre-event reference.

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07.
arXiv (CS.LG) 2026-06-12

Universal Time Series Generation with Neural Controlled Differential Equations

Authors:
Torben Berndt↗Elyes Farjallah↗Leif Seute↗Raeid Saqur↗Benjamin Walker↗Jan St\"uhmer↗

arXiv:2605.28507v2 Announce Type: replace Abstract: Recent work on the sequence universality of State Space Models (SSMs) has introduced efficient, maximally expressive continuous-time approaches for time-series modelling. While these works focus on discriminative settings, we extend this perspective to generative time-series modelling by proving that maximally expressive Structured Linear Controlled Differential Equations (SLiCEs) are universal time-series generators, in the sense that they can approximate the induced path laws of continuous causal pushforwards on compact latent sets in $W_\infty$. Building on these theoretical results, we propose Generative SLiCEs (G-SLiCEs), a maximally expressive continuous-time model for flow matching on path-space. Empirically, we show that expressivity improves performance in probabilistic forecasting and downstream tasks, while retaining the advantages of continuous-time models such as generalising to arbitrary observation grids. This is particularly beneficial for irregular grids, where fixed-grid models often struggle.

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09.
medRxiv (Medicine) 2026-06-10

Optimisation of steatotic liver disease screening algorithm for resource-poor settings using machine learning

Authors:
Mettananda↗Sivasumithran↗Ranaweera↗Madhubhashini↗Ranawaka↗Pathmeswaran↗Dassanayake↗

Background The European Association for the Study of the Liver (ESAL) - Steatotic Liver Disease (SLD) screening algorithm involves two steps; initial screening with FIB-4 followed by referral for vibration-controlled transient elastography (VCTE) in patients likely to have significant fibrosis (SF). However, VCTE is not widely available in resource-limited settings. Aim To optimise the EASL SLD screening algorithm for resource-poor settings using machine learning (ML). Methods We analysed data from 964 adults aged [≥]35 years who underwent VCTE at a tertiary referral centre in Sri Lanka between November 2024 and 2025. Multiple ML models using different methods and variable combinations were trained on 80% of the dataset and tested on the remaining 20%. Best models were selected based on performance and externally validated using data from 430 patients who underwent VCTE before November 2024. Model performance was compared with the FIB-4 using confusion matrices. Results A Random Forest model incorporating age, AST, ALT, and platelet count separately, rather than using FIB-4, outperformed. The all-variable ML model showed the best predictive performance for SF, with accuracy of 77.2%, recall of 0.762, precision of 0.778, and AUC-ROC of 0.818. The variables used in the model, in descending order of feature importance, were AST, platelet count, BMI, ALT, age, diabetes mellitus, hypertension, dyslipidaemia, sex, family history, hypothyroidism, diabetes complication and smoking. External validation demonstrated 75.1% accuracy and an AUC of 0.779. When used as the first step of the SLD screening algorithm, the all-variable ML model identified 37 (17.1%) additional true positives and reduced false-negative diagnoses by 50% compared with FIB-4. Conclusions ML-based models were more effective than the FIB-4 score as the first-line screening tool for VCTE referral, substantially improving the identification of patients with significant fibrosis in this South Asian cohort.

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

Beyond the Linear Separability Ceiling: Aligning Representations in VLMs

Authors:
Enrico Vompa↗Tanel Tammet↗Mohit Vaishnav↗

A challenge in advancing Visual-Language Models (VLMs) is determining whether their failures on abstract reasoning tasks, such as Bongard problems, stem from flawed perception or faulty top-down reasoning. To disentangle these factors, we introduce a diagnostic framework centered on the Linear Separability Ceiling (LSC), the performance achievable by a linear classifier on a VLM's raw visual embeddings. Applying this framework to state-of-the-art VLMs, we uncover a pervasive ''alignment gap'', where most models fail to generatively outperform the linear separability of their representations. We find that the few models surpassing this ceiling do so via two mechanisms: by further refining visual representations into a more linearly separable format or by executing non-linear decision logic. We demonstrate that this bottleneck is not a fundamental limitation but a solvable visual alignment issue. Our method augments standard next-token prediction with a contrastive objective to restructure the visual manifold into a more one-dimensionally linear geometry, improving image-to-image comparison and enabling models to significantly surpass the LSC on abstract compositional reasoning tasks.

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11.
Science (Express) 2026-05-21

DNA polymerization activates RNA cleavage of a reverse transcriptase–like antiviral enzyme | Science

Authors: Unknown Author

Defense-associated reverse transcriptases (DRTs) transcribe noncoding RNAs (ncRNAs) for antiviral defense, but the mechanisms of ncRNA-independent DRTs remain unclear. In this work, we show that a single DRT4 mediates RNA-targeting antiphage defense by integrating DNA polymerase, exonuclease, and RNA endonuclease activities. First, through an equilibrium between its DNA polymerase and exonuclease activities, DRT4 senses phage infection, as elevated dNTP levels shift the equilibrium toward polymerase activity, thereby promoting protein-primed single-stranded DNA (ssDNA) synthesis. Second, ssDNA of sufficient length, phage DNA-binding proteins, and deoxyguanosine triphosphate collectively activate an unusual RNA endonuclease activity of DRT4, excising 3′–guanosine monophosphate from both phage and host RNA to terminate infection. These findings reveal a distinctive immune strategy combining nucleic acid synthesis and degradation, expanding the functional landscape of DRTs for new DNA- and RNA-processing technologies.

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

Mind the Gap: Diagnosing Constraint Discovery Failures in Text-in-Image Editing

Authors:
Rui Gui↗

A key challenge in multimodal reasoning is determining which visual dependencies become relevant under a specific task, rather than merely recognizing visible content. We study this through edit-induced constraint discovery in text-in-image editing, a controlled diagnostic setting where a local text change can activate secondary consistency constraints: given a valid editing instruction and an image, can a model identify the secondary regions that must also change? Across 461 diagnostic cases, four MLLMs, and 19 constraint subtypes, models recover only 46% case-level macro recall under unguided prompting versus 94% when constraints are explicitly provided, suggesting that a substantial portion of the failure arises when models must decide which unstated dependencies to surface. Oracle-field decomposition shows that case-specific causal explanations are the most effective partial guidance (0.782 recall), above region names (0.610) or type labels (0.646), suggesting that edit-specific causal cues account for much of the oracle gain. A downstream experiment further shows that higher self-discovery recall does not necessarily improve task performance: unverified self-discovery introduces false positives that offset recall gains, motivating precision-aware constraint elicitation.

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13.
arXiv (quant-ph) 2026-06-12

Observation of Non-Gaussian Magnon Dynamics in a Two-Dimensional Long-Range XY Model

Authors:
S. -A. Guo↗J. -Y. Tan↗J. Ye↗Y. Jiang↗L. Zhang↗Y. -X. Chen↗H. -J. Chen↗H. -Y. Hu↗W. -X. Guo↗B. -X. Qi↗L. He↗Z. -C. Zhou↗…

arXiv:2606.13499v1 Announce Type: new Abstract: Non-Gaussian evolution of high-order spin correlations characterizes important properties of quantum many-body systems. In practice, decoherence, statistical fluctuation and miscalibration of experimental parameters all hinder the witness of non-Gaussian dynamics. Here we demonstrate the crossover between Gaussian and non-Gaussian dynamics on a two-dimensional XY model with long-range and spatially structured interaction using a trapped ion quantum simulator. We prepare different initial densities of magnon excitations and verify the dynamics of single-spin observables for the engineered Hamiltonian. Then we compare the high-order spin correlations with the mean-field solution and the Holstein-Primakoff approximation, and demonstrate the non-Gaussian behavior in a way independent of the calibration errors. Our work provides a verifiable path from classically simulatable dynamics to regimes where quantum advantage may emerge.

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14.
bioRxiv (Bioinfo) 2026-06-11

GeroEngine: Generative single-cell aging trajectories reveal a bidirectionally traversable identity core and direction-specific inflammatory remodeling

Authors:
Bhak↗Jeon↗

Single-cell RNA sequencing (scRNA-seq) maps aging tissues at high resolution but is destructive, preventing longitudinal tracking; dropout and zero-inflation artifacts, amplified by shift-invariant linear simulations, confound age-associated variability. We developed GeroEngine, a technical-artifact-aware framework combining VAE-based trajectory simulation, LOPO cross-validation, linear baselines, reverse traversal, and reverse-directed network inference. In microglia and HSCs, the VAE reduced technical-artifact carryover while preserving trajectory heterogeneity and improving alignment to artifact-reduced reference manifolds. Consensus GeroTargets and GeroRegulators defined tissue-specific GeroNetworks organized into three pillars: lineage/replication identity collapse, a sex-dimorphic endocrine/stress core, and inflammatory remodeling. Forward and reverse simulations aligned to the common young[->]old aging axis revealed a sign-coherent, direction-specific program: identity/replication targets were bidirectionally recovered, whereas MHC/NF-{kappa}B inflammatory programs were preferentially forward-recovered. These results support identity collapse as a deep traversable core of aging and nominate upstream homeostatic restoration over downstream inflammatory suppression.

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

GPT-Based Fast Simulation of CLAS12 Detector Hits via Conditional Autoregressive Generation

Authors:
Cole Granger↗James Giroux↗Richard Tyson↗Maurizio Ungaro↗Cristiano Fanelli↗

arXiv:2606.16035v1 Announce Type: cross Abstract: Modern particles physics experiments have demonstrated an increasing need for fast, high-fidelity detector simulation as detector components have improved and subsequent computational requirements approach the limits of available resources. Recently, deep generative models have emerged as a promising alternative to traditional Monte-Carlo methods, with recent works drawing inspiration from large language models (LLMs) and self-supervised next-token prediction methods. In this work, we present an application of a GPT-style autoregressive transformer as a fast surrogate model for the calorimeter inside the CLAS12 experiment at the Thomas Jefferson National Accelerator Facility. The model is conditioned on incident momentum and generates realistic detector hits autoregressively across all nine calorimeter layers as sequences of strip, ADC, and TDC tokens. We demonstrate that the model faithfully reproduces hit multiplicity, spatial distributions, energy deposits, and the energy-momentum response of the electromagnetic calorimeter. The generator achieves inference rates exceeding 700 events per second on a single GPU, providing a substantial speedup over traditional Geant4-based simulations while maintaining physics fidelity essential for high-luminosity experimental programs.

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

Evaluating Pluralism in LLMs through Latent Perspectives

Authors:
Laura Majer↗Jan \v{S}najder↗Martin Tutek↗

The growing need to represent diverse perspectives has increased interest in pluralistic LLM generation. Although difficult to operationalize, identifying perspectives expressed in text would provide clear guidance on pluralistic alignment and more clearly articulate the pluralistic gap in LLM generation. While models have been shown to reduce the diversity of training data and generate homogeneously, this has been demonstrated primarily on multiple-choice questionnaires or using high-level characteristics of free-form text. In this paper, we introduce and implement a domain-agnostic multi-layered framework for unsupervised extraction of perspectives suitable for identifying the pluralistic gap in LLM-generated text. We evaluate our framework on book reviews, a highly opinionated dataset representing diverse perspectives, and compare various prompts and models. Our results show that while some models and prompting techniques come close to covering a broad spectrum of perspectives, rarer perspectives remain disproportionately underrepresented, resulting in distributions that diverge from human text.

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

HiMPO: Hindsight-Informed Memory Policy Optimization for Less-Entangled Credit in Long-Horizon Agents

Authors:
Jiangze Yan↗Yi Shen↗Wenjing Zhang↗Jieyun Huang↗Zhaoxiang Liu↗Ning Wang↗Kai Wang↗Shiguo Lian↗

Long-horizon agents rely on memory mechanisms to compress interaction history, but optimizing memory writing faces a distinct credit assignment challenge: a memory update may be rewarded or penalized due to downstream tool failures, noisy observations, or reasoning errors rather than its own contribution. This causally entangled credit can lead agents to discard useful evidence or preserve irrelevant information. We propose HiMPO, a Hindsight-Informed Memory Policy Optimization framework for assigning less-entangled credit to memory-writing actions in long-horizon agents. HiMPO first estimates the local utility of a memory update by comparing the task-relevant information recoverable from the previous and updated memories under the same pre-write state. It then uses hindsight relevance as a bounded retrospective filter that attenuates memory credit when local utility is not supported by the target outcome. The resulting memory-specific advantage is applied only to memory tokens, while trajectory-level rewards optimize the rest of the agent behavior. Across judge-based open-domain tasks and objective compressive-memory QA, HiMPO improves over strong memory-based and RL-based baselines while preserving compressed-context efficiency. Controlled interventions further show that HiMPO reduces blame leakage from tool-induced errors and improves attribution fidelity of memory updates.

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18.
medRxiv (Medicine) 2026-06-12

Deconvolution-based cell-type specific DNA methylation-wide and transcriptome-wide association studies identify risk CpG sites and genes associated with colorectal cancer risk

Authors:
Li↗Xu↗Wang↗Wen↗Shu↗Yang↗X.-o↗Cai↗Long↗Singh↗Lau↗K. S↗…

Bulk tissue-based DNA methylation-wide (MWAS) and transcriptome-wide association studies (TWAS) have identified CpG sites and genes associated with colorectal cancer (CRC) risk, but do not account for cellular heterogeneity. To address this, we developed a deconvolution-informed framework to infer cell-type specific DNA methylation and gene expression profiles from bulk normal colon tissues using reference single-cell epigenomic and transcriptomic datasets. We performed cell-type specific MWAS (ctMWAS) using deconvoluted DNA methylation data from 293 normal colon samples and conducted cell-type specific TWAS (ctTWAS) using deconvoluted gene expression data from 707 normal colon samples. Genetically predicted methylation and expression models were integrated with CRC GWAS summary statistics (78,473 cases and 107,143 controls) to identify risk-associated CpG sites and genes. Through ctMWAS, ctTWAS, and colocalization analyses, we identified 178 significant cell-type-specific CpG sites in 106 loci and 68 risk genes in 40 loci, including 26 previously unreported loci. Through additional integrative methylation-gene analysis, we prioritized 132 candidate risk genes, the majority of which were supported by multi-omics evidence and stage-specific dysregulation across the adenoma-carcinoma and serrated-carcinoma progression pathways. Pathway enrichment analyses implicated pathways involved in DNA double-strand break repair, TP53 regulation, TGF-{beta} signaling, and innate immune responses. Among prioritized genes, 14 were identified as putative druggable targets linked to 90 FDA-approved or clinical-stage drugs. Experimental validation supports an oncogenic role for SF3A3. These findings demonstrate that deconvolution-informed integrative analyses enable cell-type-resolved identification of epigenetic and transcriptional mechanisms underlying CRC susceptibility and provide insights into disease biology, prevention, and therapeutic target discovery.

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19.
arXiv (CS.LG) 2026-06-18

A Survey on Data-Driven Models for Soil Moisture Regression and Classification

Authors:
Ilektra Tsimpidi↗George Georgoulas↗Vidya Sumathy↗George Nikolakopoulos↗

arXiv:2606.18316v1 Announce Type: new Abstract: Soil Moisture (SM) modelling constitutes a complex spatiotemporal learning problem characterised by nonlinear environmental interactions, heterogeneous data sources, and limited ground observations. Physics-based approaches, such as water balance models, rely on explicit hydrological equations and high-quality inputs, but their computational cost and scalability limitations restrict large-scale deployment. Data-driven artificial intelligence (AI) methods have emerged as flexible alternatives, enabling the extraction of empirical relationships between soil moisture and environmental variables with reduced modelling assumptions. This work presents a structured survey of AI-based models for soil moisture estimation and classification. Existing approaches are organized into five categories: (a) statistical time-series models, (b) geostatistical methods (c) classical machine learning (ML) models, (d) Deep Learning (DL) models and (e) Probabilistic/Bayesian methods. These models leverage historical soil moisture records, meteorological variables, vegetation indices, topography, soil characteristics, and geolocation data to perform regression or classification tasks.

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

Overcoming Rank Collapse in Feedback Alignment

Authors:
Gauthier Boeshertz↗Razvan Pascanu↗Claudia Clopath↗

arXiv:2606.11123v2 Announce Type: replace Abstract: Backpropagation (BP) is widely viewed as biologically implausible, in part because it requires feedback weights to be the transpose of forward weights for error propagation. Interestingly, when training a network with fixed random feedback weights to circumvent this issue, learning aligns the forward weights with the feedback weights, leading the backpropagated error signal to become an approximation of the standard gradient used by BP. This process, called Feedback Alignment (FA), occurs in MLPs and very shallow CNNs but does not scale well to deeper architectures. In this work, we first investigated differences between BP and FA models, trained on CIFAR10, specifically focusing on the effective rank of the signal. We found that the FA error has a considerably lower rank and hence is constrained to a lower-dimensional subspace compared to BP, limiting exploration of the parameter space. Motivated by this observation, we evaluated two mechanisms for increasing the effective dimensionality of FA: Muon, an optimiser that orthogonalises weight updates; and hidden activity normalisation, which promotes activation orthogonality. Across larger architectures and benchmarks, we find that these methods consistently improve over FA baselines, for example, on CIFAR100 with a Resnet-18, accuracy increases by 9 percentage points. Our results identify low-dimensional gradient dynamics as a key obstacle to scaling FA and suggest that inducing higher-dimensional update geometry is a promising route toward scaling alternatives to backpropagation.

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21.
arXiv (CS.LG) 2026-06-12

Learning-Augmented Approximation for Unrelated-Machines Makespan Scheduling

Authors:
Kaito Baba↗Evripidis Bampis↗Giorgos Mitropoulos↗

arXiv:2606.13133v1 Announce Type: cross Abstract: Recently, Antoniadis et al. (ICLR 2025) proposed a framework for incorporating predictions to approximate NP-hard selection problems. Despite its simplicity, this approach tightly matches theoretical lower bounds, making its generalization highly compelling. We address an open question raised in the work of Antoniadis et al., concerning the extension of this approach to other important problems outside the class of selection problems, such as scheduling. We develop a learning-augmented algorithm for the makespan minimization problem on unrelated machines, denoted by $R\|C_{\max}$. By using predictions of heavy job assignments, we achieve a polynomial-time $(1+\varepsilon)$-approximation for accurate predictions that smoothly degrades to a worst-case 2-approximation as the error increases. We conclude our work with an empirical analysis of our method.

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22.
medRxiv (Medicine) 2026-06-22

Panel-level multilocus methylation quantification in native cell-free DNA by PCR-compatible sequential enzymatic processing

Authors:
Vaquer↗C. C↗Wetten↗P. A↗Garcia Samartino↗Rodriguez↗J. D↗Manzino↗N. R↗Perez Ravier↗Angeloni↗A. R↗…

DNA methylation is informative for liquid biopsy, but low template abundance, distributed methylation signals and workflow complexity limit implementation. Here we present Delta-HLD, a PCR-compatible methylation assay platform that quantifies methylation directly in native DNA through sequential hybridization, ligation and methylation-sensitive digestion. The assay co-reports methylation-dependent signals from multiple loci through a shared amplification architecture, generating a single panel-level PCR readout. We established the chemistry, optimized panel size and composition through model-guided experiments, and implemented the assay as a triplex qPCR workflow with per-sample internal process controls. Plasma proof-of-concept analyses showed discriminatory signal in CRC and proof-of-concept transferability to hepatocellular carcinoma. Additional platelet-retaining experiments identified a strategy to increase recovery of analyzable circulating templates while reducing genomic DNA recognition. Delta-HLD provides a compact PCR-compatible framework for low-input methylation analysis without base conversion.

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23.
medRxiv (Medicine) 2026-06-15

The clinical utility of functional testing in fibroblasts to diagnose primary mitochondrial disease

Authors:
Van Hove↗J. L. K↗Friederich↗M. W↗R. A↗Lee↗J. C↗Knight↗K. M↗Donovan↗T. E↗Silveira↗…

Genome sequencing of the heterogeneous primary mitochondrial disorders (PMD) frequently reveals variants of uncertain significance that require functional tests for diagnosis, and does not identify variants in all patients. We analyzed mitochondrial enzyme assays, blue native polyacrylamide gel electrophoresis (BN-PAGE) with in-gel activity staining, complex I assembly blot, and select protein abundances in fibroblasts of a case series of 204 PMD patients divided into functional classes, in comparison to 51 controls and 53 differential diagnostic conditions. Overall, sensitivity and specificity for respiratory chain enzyme assays were 46% and 93% respectively, for BN-PAGE 40% and 98%, for complex I assembly assay 49% and 99%. The overall sensitivity of all tests was 76%, specificity 93%, with positive predictive value 96% and negative predictive value 67%. Categories with high sensitivity were isolated complex deficiencies, nuclear DNA-encoded mitochondrial protein synthesis defects, co-factor defects, and mitochondrial amino-acyl-tRNA synthetase conditions when aided by protein abundance. Mitochondrial DNA mutations and maintenance disorders showed poor sensitivities. Secondary dysfunctions were rare. A complete battery of functional tests showed strong diagnostic clinical utility in fibroblasts.

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24.
PLOS Computational Biology 2026-06-02

PepAnno: A structure-aware deep learning framework for bioactive peptide prediction, structural visualization, and physicochemical profiling

Authors:
Enyan Liu↗

by Enyan Liu, Yueming Hu, Liya Liu, Yifan Chen, Shilong Zhang, Sida Li, Haoyu Chao, Luyao Xie, Yi Shen, Liangwei Wu, Julio Raúl Fernández Massó, Ming Chen Peptides are gaining prominence as therapeutic candidates due to their diverse physiological functions and structural simplicity. Although multiple computational tools exist for bioactive peptide prediction, many suffer from limitations such as non-intuitive interfaces, sequence-only representations, insufficient structural awareness, restricted interpretability, or fragmented analysis workflows, leading to reduced research efficiency and higher costs. To address these challenges, we present PepAnno (https://bis.zju.edu.cn/pepanno/), a comprehensive and user-friendly web server for multi-functional peptide annotation. PepAnno is powered by a novel structure-aware, multi-view geometric deep learning framework that integrates pre-trained sequence embeddings with predicted 3D structural graphs through a dual-stream architecture combining a Transformer and a GATv2 network. A cross-modal attention mechanism is employed to effectively fuse semantic and geometric representations, enabling accurate multi-task prediction across 7 key bioactivities, including antimicrobial and anticancer properties. Comprehensive evaluation on seven curated bioactivity datasets demonstrates that PepAnno achieves robust and competitive predictive performance across tasks, consistently outperforming or matching existing methods in terms of discrimination and stability. Beyond functional prediction, PepAnno provides automated calculation of physicochemical properties, structure visualization, and access to an integrated repository of peptide-related databases and tools. By enabling one-click peptide annotation, PepAnno offers an efficient and interpretable solution for large-scale peptide analysis and facilitates downstream experimental design and peptide-based drug discovery.

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25.
arXiv (quant-ph) 2026-06-12

Information gain and measurement disturbance for quantum agents

Authors:
Arthur O. T. Pang↗Noah Lupu-Gladstein↗Y. Batuhan Yilmaz↗C. Pria Dobney↗Rui Jie Tang↗Aharon Brodutch↗Aephraim M. Steinberg↗

arXiv:2402.08060v3 Announce Type: replace Abstract: The traditional formalism of quantum measurement (hereafter ``TQM'') describes processes where some properties of quantum states are extracted and stored as classical information. While TQM is a natural and appropriate description of how humans interact with quantum systems, it is silent on the question of how a more general, quantum, agent would do so. How do we describe the observation of a system by an observer with the ability to store not only classical information but quantum states in its memory? In this paper, we extend the idea of measurement to a more general class of sensors for quantum agents which interact with a system in such a way that the agent's memory stores information (classical or quantum) about the system under study. For appropriate sensory interactions, the quantum agent may ``learn'' more about the system than would be possible under any set of classical measurements – but as we show, this comes at the cost of additional measurement disturbance. We experimentally demonstrate such a system and characterize the tradeoffs by considering the channel capacity required to erase the effect of a measurement.

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