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01.
arXiv (CS.LG) 2026-06-19

Understanding Key Features of Time Series Foundation Models from Epidemic Forecasting

arXiv:2606.19560v1 Announce Type: new Abstract: Seasonal influenza infects millions of people and causes substantial morbidity and mortality in the United States each year, making accurate short-term forecasting a core public-health need. Reliable forecasts of epidemic time series can inform vaccination timing, hospital staffing, and resource allocation, yet the comparative behavior of modern forecasting architectures on infectious-disease surveillance data remains insufficiently characterized. We address this gap through a systematic evaluation of regional influenza forecasting using influenza-like illness surveillance and influenza-associated hospitalization time series under both temporal and spatial generalization settings for 1-4-week-ahead prediction. We compare classical neural network architectures, numerical transformer-based models, pretrained time series foundation models, and LLM-based forecasting approaches. Across tasks, we demonstrate that a mixture-of-experts model that fuses multiple pretrained forecasters achieves the strongest overall performance, indicating that heterogeneous pretrained representations provide complementary predictive information. Our results further show that numerical transformer-based models produce reliable forecasts, while pretraining provides the largest gains at longer horizons, particularly when the pretraining domain is mechanistically aligned with influenza dynamics. In contrast, LLM-based time series methods underperform relative to numerical forecasters in this setting. Finally, we examine hospitalization information as both an auxiliary covariate and a pretraining source. Hospitalization signals provide complementary improvements in selected settings and clarify when additional surveillance streams enhance the robustness of multi-horizon forecasting. These findings provide actionable guidance on model selection, pretraining strategy, and auxiliary-signal use for influenza preparedness.

02.
arXiv (math.PR) 2026-06-16

Quantitative Oppenheim Conjecture for Random Quadratic Forms and Optimal Variance Bounds in Function Fields

arXiv:2606.16699v1 Announce Type: cross Abstract: We prove a quantitative version of Oppenheim's conjecture in the function field setting. In order to do so, we compute the higher moments of the Siegel transform. In particular, we find an optimal bound on the variance of the number of lattice points in a set. Moreover, we compute the exact variance of the number of lattice points in a ball, which is of independent interest.

03.
arXiv (CS.CL) 2026-06-15

UP-NRPA: User Portrait based Nested Rollout Policy Adaptation for Planning with Large Language Models in Goal-oriented Dialogue Systems

To address the challenge that current dialogue policy planning methods struggle to dynamically adapt to diverse user characteristics, this paper proposes a User Portrait based Nested Rollout Policy Adaptation (UP-NRPA) online framework with Large Language Models. In contrast to conventional approaches dependent on model training and require offline reinforcement learning policy models for user groups, UP-NRPA enables dynamic customization of dialogue strategies through an adaptive mechanism. This is achieved by leveraging real-time user feedback alongside personality, preferences, and objectives mapped from the current user portrait, thereby adapting to user characteristics without offline reinforcement learning. In collaborative and non-collaborative dialogue benchmarks, UP-NRPA demonstrated considerable benefits, achieving an impressive 100% success rate in multiple dialogue tasks. Particularly in negotiation tasks, the sale-to-list ratio (SL) increased by 56.41%. This demonstrates that UP-NRPA can adapt to diverse user needs without requiring a training mechanism, enabling the dialogue system to adapt to user characteristics.

04.
arXiv (CS.AI) 2026-06-11

What Limits Does Quantization Place on Dense Top-$k$ Retrieval? A Theoretical Study

arXiv:2606.11780v1 Announce Type: cross Abstract: We establish conditions for embedding a corpus of $N$ documents as $d$-dimensional vectors such that every $k$-subset $S \subseteq [N]$ is realizable as a result of top-$k$ retrieval by some query vector. Recent work shows that $d = O(k)$ suffices for such embeddings to exist in $\mathbb{R}^d$, independently of $N$. We theoretically prove that this corpus-independent bound is specific to infinite precision. With $B$ bits per coordinate, perfect top-$k$ retrieval requires $Bd = \Omega(k \ln N)$; thus, at any fixed precision, the dimension must grow at least logarithmically with $N$. Specializing to a $\ell_2$-normalized $B$-bit uniform scalar quantization model, we also identify a threshold on the precision $B^{*} = O(\ln \ln N)$ below which no dimension suffices, together with two further regimes that bound the feasible $(B, d)$ pairs. Our result implies that in practical vector databases and dense retrieval systems where quantization is standard, the embedding dimension and possibly the precision must grow with the corpus size.

05.
arXiv (CS.LG) 2026-06-11

Discovery and inference beyond linearity for epidemiological data by integrating Bayesian regression, tree ensembles and Shapley values

arXiv:2505.00571v3 Announce Type: replace-cross Abstract: Machine Learning (ML) is gaining popularity in epidemiology and healthcare studies for hypothesis-free discovery of risk and protective factors. ML is strong at discovering nonlinearities and interactions, but this power is compromised by a lack of reliable inference. Although Shapley values provide local measures of features' effects, valid uncertainty quantification for these effects is typically lacking, thus precluding statistical inference. We propose RuleSHAP, a framework that addresses this limitation by combining a dedicated Bayesian sparse regression model with an improved tree-based rule generator and Shapley value attribution. RuleSHAP provides detection of nonlinear and interaction effects, with uncertainty quantification at the individual level as a key contribution. We derive an efficient formula for computing marginal Shapley values within this framework. We apply RuleSHAP to data from an epidemiological cohort to detect and infer several effects for high cholesterol and blood pressure, such as nonlinear interaction effects between features like age, sex, ethnicity, BMI and glucose level. To conclude, we demonstrate the validity of our framework on simulated data.

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

E-mem: Multi-agent based Episodic Context Reconstruction for LLM Agent Memory

arXiv:2601.21714v5 Announce Type: replace Abstract: The evolution of Large Language Model (LLM) agents towards System~2 reasoning, characterized by deliberative, high-precision problem-solving, requires maintaining rigorous logical integrity over extended horizons. However, prevalent memory preprocessing paradigms suffer from destructive de-contextualization. By compressing complex sequential dependencies into pre-defined structures (e.g., embeddings or graphs), these methods sever the contextual integrity essential for deep reasoning. To address this, we propose E-mem, a framework shifting from Memory Preprocessing to Episodic Context Reconstruction. Inspired by biological engrams, E-mem employs a heterogeneous hierarchical architecture where multiple assistant agents maintain uncompressed memory contexts, while a central master agent orchestrates global planning. Unlike passive retrieval, our mechanism empowers assistants to locally reason within activated segments, extracting context-aware evidence before aggregation. Evaluations on the LoCoMo benchmark demonstrate that E-mem achieves over 54\% F1, surpassing the state-of-the-art GAM by 7.75\%, while reducing token cost by over 70\%.

07.
arXiv (CS.AI) 2026-06-15

Universal Manipulation Exoskeleton: Learning Compliant Whole-body Policies with Real-time Torque Feedback

arXiv:2606.14218v1 Announce Type: cross Abstract: For robots to work safely in household environments, they need to be compliant and react to torque and force feedback during contact. However, the majority of existing data collection pipelines still lack the ability to capture force and torque data for learning active compliant policies. In this paper, we present Universal Manipulation Exoskeleton (UME), an upper-limb exoskeleton that provides real-time haptic torque feedback while recording whole-arm configurations and joint torque signals for teleoperation. With transparent torque feedback, human operators can even unsheathe kinematically constrained objects while blindfolded. UME is low-cost, lightweight, and portable. Equipped with an embedded IMU, it enables teleoperation for mobile manipulation. With our proposed universal retargeting algorithm, UME can teleoperate a range of robots, including the 7DoF OpenArm, 7DoF Franka, and 6DoF X-ARM. We demonstrate that this combination of capabilities enables learning bimanual, whole-body, and active compliant policies that operate effectively in highly constrained spaces. The learned robust autonomous policies achieve high success rates across a variety of tasks, including long-horizon mobile manipulation, force-mediated box flipping, visually occluded box pushing, and space-constrained tabletop manipulation. Videos, code, and additional information can be found at https://ume-exo.github.io.

08.
arXiv (CS.AI) 2026-06-15

Quantized Evolution Strategies: High-precision Fine-tuning of Quantized LLMs at Low-precision Cost

arXiv:2602.03120v2 Announce Type: replace-cross Abstract: Post-Training Quantization (PTQ) is essential for deploying Large Language Models (LLMs) on memory-constrained devices, yet it renders models static and difficult to fine-tune. Standard fine-tuning paradigms, including Reinforcement Learning (RL), fundamentally rely on backpropagation and continuous weights to compute gradients. Thus they cannot be used on quantized models, where the parameter space is discrete and non-differentiable. While Evolution Strategies (ES) offer a backpropagation-free alternative, optimization of the quantized parameters can still fail due to vanishing or inaccurate gradient estimation. This paper introduces Quantized Evolution Strategies (QES), an optimization paradigm that performs full-parameter fine-tuning directly in the quantized space. QES is based on two innovations: (1) it integrates accumulated error feedback to preserve high-precision weight updating signals, and (2) it utilizes a stateless seed replay to reduce memory usage to low-precision inference levels. QES significantly outperforms the state-of-the-art zeroth-order fine-tuning methods on a variety of tasks, making direct fine-tuning for quantized models possible. It therefore opens up the possibility for scaling up LLMs entirely in the quantized space. The source code is available at https://github.com/dibbla/Quantized-Evolution-Strategies .

09.
arXiv (CS.AI) 2026-06-19

Contagion Networks: Evaluator Bias Propagation in Multi-Agent LLM Systems

Authors:

arXiv:2606.20493v1 Announce Type: cross Abstract: When large language models serve as evaluators in multi-agent systems, their systematic evaluation biases propagate through the agent network. We introduce Contagion Networks, a formal framework for measuring how evaluator biases spread across interacting LLM agents. In a controlled 3-agent experiment using DeepSeek-chat with three distinct evaluator bias profiles (structured, balanced, evidence-based), we measure the Cross-Agent Contagion Matrix Gamma_3 and find that evaluator biases consistently propagate between agents (gamma in [0.157, 0.352]), even within the same underlying model. We identify three propagation regimes governed by the spectral radius rho(Gamma_N), and demonstrate that homogeneous-model agents produce contagion coefficients 3-5x weaker than cross-model coefficients observed in prior work (MM-EPC: gamma approx 0.85-1.3), placing them in the suppression regime. We show that increasing evaluator committee size from k=1 to k=3 reduces effective contagion by 72.4%, providing an actionable mitigation strategy. We release the open-source Contagion Network experimental framework.

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

Characterization of Gaussian Universality Breakdown in High-Dimensional Empirical Risk Minimization

arXiv:2604.03146v3 Announce Type: replace-cross Abstract: We study high-dimensional convex empirical risk minimization (ERM) under general non-Gaussian data designs. By heuristically extending the Convex Gaussian Min-Max Theorem (CGMT) to non-Gaussian settings, we derive an asymptotic min-max characterization of key statistics, enabling approximation of the mean $\mu_{\hat{\theta}}$ and covariance $C_{\hat{\theta}}$ of the ERM estimator $\hat{\theta}$. Specifically, under a concentration assumption on the data matrix and standard regularity conditions on the loss and regularizer, we show that for a test covariate $x$ independent of the training data, the projection $\hat{\theta}^\top x$ approximately follows the convolution of the generally non-Gaussian distribution of $\mu_{\hat{\theta}}^\top x$ with an independent centered Gaussian variable of variance $\mathrm{tr}(C_{\hat{\theta}} \mathbb{E}[xx^\top])$. This result clarifies the scope and limits of Gaussian universality for ERMs. Additionally, we prove that any $\mathcal{C}^2$ regularizer is asymptotically equivalent to a quadratic form determined solely by its Hessian at zero and gradient at $\mu_{\hat{\theta}}$. Numerical simulations across diverse losses and models are provided to validate our theoretical predictions and qualitative insights.

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

Operator Learning for efficient Quantum Computation

arXiv:2606.20184v1 Announce Type: new Abstract: An efficient implementation of quantum algorithms is often hindered by the lack of efficient primitives for operators and state preparation. This limits both the ability of near-term quantum hardware to simulate complex problems and the potential of fault-tolerant algorithms to achieve practical quantum advantage. To address this, we propose a full-stack variational framework that transforms arbitrary operators to compact quantum circuits. The resulting variational circuits can be tailored to the connectivity and long-range interaction of the target hardware. The learning process employs backpropagation together with a cost function that efficiently optimizes unitary operators and non-unitary – dense or sparse – operators using only a single ancilla qubit for block encoding. Additionally, we introduce a regularization term that reduces the approximation error. The approach is validated for both quantum mechanical and engineering applications. In the former case, we learn propagators that arise in native quantum problems – such as quantum simulation and quantum chemistry – and achieve improved resource scaling in comparison to standard Suzuki-Trotter expansions. In the latter case, we demonstrate the approach's ability to implement the second-order central finite difference approximation of the Laplace operator – relevant for solving partial differential equations – while improving upon current error metrics. The final example deals with learning a dense, non-unitary operator that arises in the analysis of inviscid potential flow around an airfoil. This universality of the framework opens the door for solving general problems beyond prototypical engineering and quantum applications.

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

Selective Rotary Position Embedding

Position information is essential for language modeling. In softmax transformers, Rotary Position Embeddings (RoPE) encode positions through fixed-angle rotations, while in linear transformers, order is handled via input-dependent (selective) gating that decays past key-value associations. Selectivity has generally been shown to improve language-related tasks. Inspired by this, we introduce Selective RoPE, an input-dependent rotary embedding mechanism, that generalizes RoPE, and enables rotation in arbitrary angles for both linear and softmax transformers. We show that softmax attention already performs a hidden form of these rotations on query-key pairs, uncovering an implicit positional structure. We further show that in state-space models and gated linear transformers, the real part manages forgetting while the imaginary part encodes positions through rotations. We validate our method by equipping gated transformers with Selective RoPE, demonstrating that its input-dependent rotations improve performance in language modeling and on difficult sequence tasks like copying, state tracking, and retrieval.

13.
bioRxiv (Bioinfo) 2026-06-22

PhaseWY: A pipeline for haplotype phasing, sex chromosome identification and extraction of sex-limited sequences

Sex chromosomes are central to many ecological and evolutionary processes. Evidence has accumulated that sex chromosome systems vary extensively in age, turnover and transitions, motivating renewed efforts to study the diversity of sex chromosome systems across the tree of life. However, successful genomic detection of sex chromosomes depends on several factors, including the size and divergence time, background genetic diversity, and the number of sequenced females and males. In addition, technical challenges associated with sequencing and analysing the sex-limited Y/W chromosome remain. Here, we present PhaseWY, an automated Snakemake pipeline that uses whole-genome sequencing data from multiple female and male individuals to identify sex-chromosomal regions and extract the corresponding Y/W sequences. PhaseWY (i) detects sex differences in alignment depth, (ii) applies read-based and statistical haplotype phasing, (iii) identifies sex-linked regions using haplotype clustering, and (iv) subsets autosomal, X/Z- and Y/W-linked variants for downstream analyses. We applied PhaseWY to simulated data to benchmark factors influencing sex-linkage detection and successful extraction of Y/W-linked variants. To demonstrate its practical utility, we further applied PhaseWY to the neo-sex chromosome system in Alauda larks (Alaudidae) and performed a range of downstream analyses demonstrating the scope of applications of the PhaseWY output. We conclude that PhaseWY provides an easy-to-use and reproducible tool for population-genomic analyses in non-model organisms, with particular importance for advancing our understanding of sex-chromosome evolution.

14.
arXiv (CS.LG) 2026-06-15

Cluster LOCO: Feature Importance For Interpreting Clusters

arXiv:2606.14592v1 Announce Type: cross Abstract: Clustering is widely used for exploratory analysis and scientific discovery, driving insights from market segmentation to biological data analysis, but its outputs can be difficult to interpret, audit, and reproduce as modern datasets become increasingly large and complex. Reliable use of clustering requires understanding which features drive the discovered structure, yet feature-level explanations for clustering remain scarce compared with methods in supervised learning. Furthermore, existing clustering feature importance scores are often tied to specific algorithms and data assumptions. To address these challenges, we propose Cluster LOCO (Leave-One-Covariate-Out), a family of model-agnostic feature importance scores for clustering. Cluster LOCO is built on feature occlusion and clustering generalizability, defined as whether cluster labels learned on one subset of the data can be accurately predicted on held-out samples. For any chosen clustering algorithm, Cluster LOCO quantifies a feature's importance by measuring how much its removal degrades generalizability. We first introduce Cluster LOCO-Split, which relies on data splitting, and then extend it to Cluster LOCO-MP, a minipatch ensemble-based version designed for large-scale data. Across synthetic simulations and an application to cell-type discovery in single-cell transcriptomics, we show that Cluster LOCO more reliably recovers informative features than existing clustering feature importance methods.

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

Sub-Semantic Image Segmentation

Images can be segmented based on visual cues (i.e., texture segmentation) or into objects (i.e., semantic segmentation). We propose a new category of sub-semantic image segmentation that blurs the line between the two. In sub-semantic image segmentation, language is not used to name whole objects. Instead, it is used to partition an image into stable appearance patterns that can be described by language. To do that, we couple a general-purpose vision-language model to SAM 3, a promptable segmentation backbone whose native text pathway can ground rich descriptions into masks. Simple coupling fails for a number of reasons that we identify in the paper, and we overcome them by introducing DETECTURE that resolves three concrete failure modes – language leakage between texture regions, prompt competition inside the segmentation backbone, and semantic distortion at the language-to-mask interface. Since there is no dataset of sub-semantic image segmentation, we introduce one, termed TextureADE. The new dataset is derived from the ADE20K dataset using a system we designed. We compare DETECTURE to a number of baselines and find that it achieves the strongest performance on several datasets using different metrics. Code is available at https://github.com/Scientific-Computing-Lab/TextureDetecture.

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

T2D-Bench: Evidence-Gated Evaluation of LLM Outputs for Type 2 Diabetes Using a Multi-Layer Clinical-Lifestyle Knowledge Graph

arXiv:2606.24145v1 Announce Type: new Abstract: Large language models (LLMs) can produce clinically fluent recommendations for type 2 diabetes while failing to satisfy guideline constraints or explicitly justify lifestyle-related glycemic claims. We present T2D-Bench, a reproducible benchmark and evidence-gated evaluation framework for testing whether LLM outputs satisfy explicit, graph-checkable evidence requirements. T2D-Bench is built on a multi-layer clinical-lifestyle knowledge graph that combines a biomedical spine (UMLS, DrugBank, SIDER), computable ADA Standards of Care rules, and lifestyle knowledge connected through a mechanistic bridge to glycemic laboratory effects. Across 100 structured vignettes spanning diagnosis, medication safety, and adversarial lifestyle conflicts, baseline outputs failed benchmark-defined evidence-path checks in 35% of cases for GPT-4o-mini and 33% for GPT-4o. The evidence gate detects unsupported omissions and uses constrained revision to bring outputs into verifier-level compliance with benchmark-defined evidence requirements. These results show that computable evidence constraints can make unsupported clinical omissions explicit, measurable, and correctable in diabetes-focused LLM outputs.

17.
Nature (Science) 2026-06-10

In situ nanocrystal confinement for efficient blue perovskite LEDs

Authors:

Metal halide perovskites have emerged as promising semiconductors for light-emitting diodes (LEDs) owing to their excellent luminescence properties1. However, their performance remains limited, primarily owing to the inherent contradiction between ‘high crystallinity’ and ‘small size’ in the in situ synthesis of perovskite nanocrystals on substrates. Here we report efficient blue perovskite LEDs (PeLEDs) achieved via in situ polymerization-driven nanocrystal confinement to synthesize perovskite films composed of high-quality nanocrystals. The in situ-formed polymer network imposes nanoscale spatial constraints during perovskite nanocrystal growth, enabling nanocrystals with small sizes and a high photoluminescence quantum yield of 83%. Furthermore, polymerizable monomers with sufficient coordination sites allow a prolonged lattice rearrangement of perovskite clusters, promoting the crystallinity of the nanocrystals. The synthesized perovskite nanocrystals are utilized in the fabrication of PeLEDs, resulting in an external quantum efficiency of 21.8% at 491 nm, which is among the highest performances in blue PeLEDs. This work simultaneously controls the thermal dynamics of perovskite crystallization and organic ligand reactions, which helps to advance understanding of the effect of ligand engineering on nanocrystal synthesis, benefiting the development of efficient PeLEDs and other optoelectronic technologies. Efficient blue perovskite light-emitting diodes with an external quantum efficiency of 21.8% are achieved through in situ polymerization-driven nanocrystal confinement.

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

LedgerAgent: Structured State for Policy-Adherent Tool-Calling Agents

Policy-adherent tool-calling agents in customer-service domains must maintain task states across turns while calling tools and obeying domain policies. Task states consist of relevant facts, identifiers, constraints, and conditions observed through user interaction and tool calls. In standard agents, task states are not represented separately. Observations, tool returns, and policy instructions are placed in the prompt, leaving agents to reconstruct the relevant states from the prompt each time they decide what to do next. This design makes state management implicit, creating two common failure modes. An agent may retrieve the right facts but later ground its decision in stale, missing, or incorrect information; and a syntactically valid tool call may still violate a domain policy that depends on the current task state. We introduce \textsc{LedgerAgent}, an inference-time method for tool-calling agents that maintains observed task states in a separate ledger and renders the states into the prompt. The ledger is also used to check state-dependent policy constraints before environment-changing tool calls are executed, blocking policy violations. Across four customer-service domains and a mixed panel of open- and closed-weight models, \textsc{LedgerAgent} improves average pass\textasciicircum{}k over a standard prompt-based tool-calling approach, with the largest gains under stricter multi-trial consistency metrics.

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

Reinforcement Learning Towards Broadly and Persistently Beneficial Models

As AI systems are deployed across increasingly diverse and high-stakes settings, model alignment must generalize beyond the tasks and domains seen during training. This is especially important for reinforcement learning (RL), which can introduce unexpected misalignment through reward hacking, deception, or other unintended strategies. We study whether RL on beneficial behavior, instantiated in realistic domains, can produce broad and persistent alignment generalization beyond the training distribution. We construct a dataset of realistic situations designed to measure and train beneficial traits, such as truthfulness, fairness, risk awareness, and corrigibility, spanning varied domains, including health, science, and education. We then train models with RL on this dataset and evaluate them on more than 50 independent benchmarks of alignment and beneficial behavior. Compared to a compute-matched baseline, beneficial trait RL improves performance on over 80% of these out-of-distribution benchmarks. We observe substantial out-of-distribution alignment transfer: a beneficial-behavior RL intervention entirely limited to one domain, health, produces broad improvements on non-health alignment evaluations, including reduced reward hacking, deception, and general misalignment. Finally, we study alignment persistence: whether behavior remains robustly aligned under attempts to steer models towards misalignment. Models trained with beneficial trait RL show improved persistence, including greater resistance to adversarial prompting and harmful finetuning; further work is required to isolate the sources of these effects. These results suggest that RL to reinforce beneficial behavior in realistic domains can produce models that are more robustly aligned with human flourishing.

20.
arXiv (quant-ph) 2026-06-19

Sparse Configuration Interaction for the Electronic Schrödinger Equation Revisited: Complete Basis Set Limit Complexity and Quantum-Encoding Impact

arXiv:2606.20385v1 Announce Type: new Abstract: In this article we revisit regularity results for eigenfunctions in the discrete spectrum of the electronic Schrödinger equation and study their consequences for approximation complexity. In particular, for the convergence to the complete basis set limit, it can be shown that the curse of dimensionality in the leading algebraic exponent can be mitigated. That is, for general sparse grid constructions, the main term of the convergence rate with respect to the number of degrees of freedom is independent of the number of electrons. These insights indicate potential benefits for classical numerical solvers of the electronic Schrödinger equation and also for quantum-computing approaches through new qubit-efficient wavefunction encodings.

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

Simplicity Suffices for Parameter Noise Injection in Stochastic Gradient Descent

arXiv:2606.12054v1 Announce Type: new Abstract: Injecting noise into the optimization process is a well-established technique for improving the training and generalization of deep neural networks. Yet, despite the breadth of existing approaches, it remains unclear which design choices truly matter in practice. In this work, we investigate parameter noise injection for stochastic gradient descent, focusing on two key questions: how to efficiently pair each training example with its own perturbation in mini-batch training, and whether sophisticated noise parameterizations or multi-sample gradient averaging yield meaningful gains over simpler alternatives. To address the first question, we leverage a distributional identity for linear layers that allows per-example noise injection without breaking batched computation. To address the second, we systematically compare several diagonal Gaussian parameterizations against an isotropic baseline across varying noise levels on CIFAR100. Our results consistently show that simple, lightweight strategies, isotropic noise with a single perturbed forward pass per update step, recover most of the benefit of more complex schemes. These findings suggest that simplicity suffices for parameter noise injection, and that practitioners need not resort to elaborate perturbation designs to reap the optimization and generalization benefits of noisy SGD.

22.
arXiv (CS.LG) 2026-06-19

Constrained hybrid modelling to predict microbial dynamics and organic matter turnover in soil systems

arXiv:2606.20329v1 Announce Type: new Abstract: Soil microorganisms control organic matter cycling and largely determine how soil systems can cope with and mitigate climate change and environmental threats. Representing microbial dynamics in process-based soil models is therefore critical to predict carbon cycling in soils, albeit highly challenging to inform from data. One promising approach to improve their parametrisation is the integration of genomic data, yet modelling the complex and unknown relationship between genomes and the processes the microbes are driving is an unsolved problem. In this work, we present the first hybrid modeling framework for deriving biokinetic parameter values of a process-based soil organic matter turnover model from metagenome-inferred functional traits based on DNA sequencing data. Our model predicts biokinetic parameters of the process-based model from genomic trait data with a neural network and integrates constraints from ecological theory and literature to ensure realistic behavior, even of non-observed state variables. We evaluate our method on synthetic genomic trait datasets of varying complexity and on real data, showing that our approach improves performance over multiple baselines and learns the dynamics of unmeasurable components of the process-based model effectively, even for small training datasets.

23.
PLOS Computational Biology 2026-06-01

Challenges and progress in RNA velocity: Comparative analysis across multiple biological contexts

Authors:

by Sarah Ancheta, Leah Dorman, Guillaume Le Treut, Abel Gurung, Greg Huber, Loïc A. Royer, Alejandro Granados, Merlin Lange Single-cell RNA sequencing is revolutionizing our understanding of cell state dynamics, allowing researchers to capture and quantify the transcriptomic profile of a single cell at a specific timepoint. Among the computational techniques used to predict cellular trajectories, RNA velocity has emerged as a predominant tool for modeling transcriptional dynamics. RNA velocity leverages the mRNA maturation process to generate velocity vectors that predict the likely future state of a cell, offering insights into cellular differentiation, aging, and disease progression. Although this technique has shown promise across biological fields, the performance accuracy varies depending on the RNA velocity method and dataset. We established a comparative pipeline and analyzed the performance of five RNA velocity methods on three datasets based on local consistency, method agreement, identification of driver genes, and robustness to sequencing depth. This benchmark provides a resource for scientists to understand the strengths and limitations of different RNA velocity methods.

24.
medRxiv (Medicine) 2026-06-10

Transcriptomic Architecture of Type 2 Diabetes in Human Pancreatic Islets:An Integrative Meta-Analysis and Machine Learning Framework for Biomarker Discovery

Authors:

Background. Type 2 diabetes mellitus (T2D) is defined by progressive pancreatic {beta}-cell dysfunction whose molecular underpinnings remain incompletely understood. Single-cohort transcriptomic analyses of donor islets have yielded heterogeneous gene lists of limited cross-study reproducibility, constraining both mechanistic interpretation and biomarker development. Methods. We combined two complementary analytical strategies applied to four public human islet transcriptomic cohorts (GSE25724, GSE20966, GSE38642, and GSE164416; n = 7-57 donors per contrast). For the integrative arm, three microarray datasets and one bulk RNA-seq dataset were processed independently and unified through gene-level random-effects meta-analysis, hallmark pathway scoring (GSVA/MSigDB), and iterative module refinement, yielding a two-axis disease framework. For the diagnostic arm, a consensus multi-method machine learning pipeline, combining LASSO penalized logistic regression, Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Random Forest importance scoring, was applied to 184 differentially expressed genes from the RNA-seq cohort, with all normalization steps performed within leave-one-out cross-validation (LOOCV) folds to prevent data leakage. Machine learning classification of the RNA-seq cohort was additionally subjected to external transportability testing in the independent bulk human islet RNA-seq cohort GSE50244 using an overlap-restricted reduced score and a threshold fixed in the discovery cohort. Results. Meta-analysis across all four cohorts identified 337 high-confidence T2D-associated genes (96.1% directional concordance in beta-cell-enriched tissue). These were distilled into two refined 14-gene modules: ImmuneStress (MICB, HLA-DRA, HLA-DPA1, IL1R2, and others) and BetaCellIdentitySecretion (RASGRP1, PPP1R1A, SLC2A2, and others), whose composite IsletDysfunctionScore provided the most stable cross-platform separation of non-diabetic from T2D islets (Hedges' g = 1.80, p = 9.83 x $10^-17$, $text{I}^2$= 0%). Consistent with progressive disease, IsletDysfunctionScore increased monotonically from non-diabetic to impaired glucose tolerance to T2D. Separately, the machine learning pipeline derived a 10-gene diagnostic panel: GABRA2, SLC2A2, ARG2, DKK3, PRIMA1, TAFA4, HHATL, PARVG, RNU1-70P, and the novel lncRNA ENSG00000284653, that achieved perfect discrimination in LOOCV (AUC = 1.000, sensitivity = 1.000, specificity = 1.000, zero misclassifications across all 57 donors). A leakage-verification experiment confirmed that this performance reflected genuine biological signal: global quantile normalization prior to cross-validation collapsed AUC to 0.380. External testing showed that 8 of the 10 panel genes were measurable in GSE50244. The frozen 8-gene reduced score retained strong discrimination (external AUC = 0.907), with 6 of 8 genes preserving directional concordance, but the discovery-derived threshold did not transfer because the external score distribution was shifted upward and compressed, yielding complete sensitivity but zero specificity at the frozen cutoff Conclusions. Integrating pathway-level meta-analysis with machine learning classification, we present a coherent two-axis model: immune/stress activation and loss of beta-cell identity/secretory competence, together with a compact, biologically interpretable 10-gene diagnostic signature. Panel genes converge on GABA signaling, glucose transport, arginine metabolism, WNT pathway inhibition, and a novel lncRNA, providing both mechanistic hypotheses and high-priority targets for external validation. These findings offer a reproducible transcriptomic scaffold for future mechanistic, biomarker, and clinical translation studies of human islet dysfunction. They also support external transportability of the core biological signal, while indicating that absolute operating thresholds are cohort-dependent and would require recalibration before deployment in independent datasets.

25.
arXiv (CS.CV) 2026-06-15

Clay-CNN Hybrids: Leveraging Geo-Foundational Models as Auxiliary Context for Landslide Detection

Authors:

Rapid post-event landslide mapping is essential for disaster response but remains difficult to automate due to extreme class imbalance. This study evaluates whether Clay v1.5, a Geo-Foundational Model (GFM), can improve pixel-level landslide segmentation on the Landslide4Sense (L4S) benchmark, which contains 3,799 training chips with 14 Sentinel-2 and terrain bands and approximately 2% positive pixels. We compare three strategies: Clay as the primary encoder with multi-scale residual terrain fusion, a U-Net backbone augmented with Clay semantic context at the bottleneck, and a standard U-Net baseline. The hybrid U-Net + Clay model with two-stage Low-Rank Adaptation (LoRA) achieved the best test F1 of 64.5 +/- 1.8% over three seeds, surpassing the Clay-only backbone (55.2 +/- 3.6%) and the U-Net baseline (59.9%). Clay as a standalone encoder underperformed the U-Net due to the absence of multi-scale skip connections, but its pretrained representations consistently improved performance when injected as auxiliary context. These findings suggest that GFMs are most effective for landslide detection when they complement spatially detailed convolutional architectures rather than replace them.