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

MUNI: Multimodal Unified Latent Diffusion for Coherent Any-to-Any Generation

arXiv:2606.16408v1 Announce Type: new Abstract: We introduce MUNI, an end-to-end multimodal latent diffusion framework for any-to-any generation that unifies subset-conditioned cross-modal generation and unconditional joint sampling through a shared stochastic latent. Existing multimodal generative models are largely LLM-based, which limits leveraging modality-specific generators and requires text-paired data for training. Recent diffusion- and flow-based any-to-any extensions take a different direction but still rely on text-aligned embeddings, fully-paired training, or matched-dimensionality deterministic mappings. MUNI rests on two complementary contributions, one architectural and one in the training objective. First, we extend latent diffusion to multimodal any-to-any generation end-to-end: instead of the standard two-stage recipe that precomputes a frozen latent space and then fits a prior over it, MUNI jointly trains modality-specific encoders, expressive decoders, and a single shared flow-based prior under one objective. Second, we identify that the standard aggregation rules of multimodal variational inference are insufficient once coupled with a learned prior and expressive decoders. A suitable shared latent must simultaneously satisfy coherence across generated modalities, predictive sufficiency of subset latents, and minimality of the latent content. We propose a routed training objective whose structural choices align the latent with these criteria and admit a minimal-sufficiency characterization in the realizable setting. Experiments on PolyMNIST-Quadrant-Labels and a large-scale image-text-audio benchmark show MUNI matching or exceeding the strongest baselines on conditional generation while opening its largest margins on unconditional coherence. Project page: https://muni-proj.github.io/.

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

GEAR-VLA: Learning Geometry-Aware Action Representations for Generalizable Robotic Manipulation

arXiv:2606.08530v2 Announce Type: replace-cross Abstract: Vision-Language-Action (VLA) models achieve strong benchmark performance but still struggle in real-world deployment with unseen objects, background shifts, and different robot embodiments. We argue that this stems from the lack of a unified geometry-aware manipulation representation, leaving existing VLAs vulnerable to low-level trajectory supervision, misaligned 3D features, and embodiment differences. To address this, we propose GEAR-VLA, a VLA framework for learning unified geometry-aware action representations for generalizable robotic manipulation. GEAR-VLA adopts coarse-to-fine action learning, where multi-source embodied pretraining equips the VLM with embodied reasoning and discrete action understanding before latent action tokens connect action semantics to a gradient-decoupled DiT continuous action expert. It further performs semantic-aligned 3D integration by aligning a trainable 3D spatial backbone with the VLA representation while freezing the original VLM-aligned visual pathway. To share this representation across robots, GEAR-VLA uses embodiment canonicalization, where embodiment-aware states and embodiment-invariant actions confine robot differences to the low-level interface. Extensive simulation and real-world experiments demonstrate strong generalization: GEAR-VLA achieves state-of-the-art performance on LIBERO, zero-shot LIBERO-Plus, and RoboTwin 2.0, reaches 85.9% success on AgileX and 81.0% on the pretraining-unseen LDT-01 embodiment, and obtains 90.1% success on a 6,360-trial universal grasping benchmark with 212 unseen objects. Code and models will be released at https://github.com/babynabeauty/GEAR-VLA.

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

Triangular Consistency as a Universal Constraint for Learning Optical Flow

arXiv:2606.19938v1 Announce Type: cross Abstract: We propose triangular consistency as a first-principled constraint for optical flow, which is agnostic to network architecture, supervision type, and dataset, and applies to both image-pair and multi-frame settings. This simple but powerful constraint is to compose two flows to induce a third flow and enforce consistency among the three. The composed flows may arise from (i) image pairs, yielding cycle consistency; (ii) multiple video frames, producing longer-range motion through temporal chaining; or (iii) image pairs combined with controlled synthetic transformations, which becomes data augmentation. This triangular consistency introduces negligible computational overhead and requires no additional annotations. Since it is derived directly from the geometry of optical flow, it does not rely on model-specific assumptions and serves as a ``universal'' plug-and-play component for optical flow training. Experiments show consistent improvement across supervised, unsupervised, and transfer learning settings.

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

Connections Between Pairs of Filters Improve the Accuracy of Convolutional Neural Networks

While researchers continue to find new and improved network structures for CNNs, most of the newly invented architectures still rely on the traditional pattern of stacking convolutional blocks and separating them with pointwise activation functions. However, there are drawbacks to a network purely building on pointwise nonlinearities. One alternative is to introduce a pairwise connection between two filters of a network. Typical connection functions use multiplications or the minimum operation to realize logical AND connections. In this paper, we go one step further by demonstrating that CNNs can benefit from more general connections, which include parameters that are learned. With such parameters, the network is able to implement different connections in different network layers and better adapt the connection function to the task at hand.

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

On-site interactions in quantum thermal machines: efficiency, rectification and entanglement beyond local and global master equations

arXiv:2606.14593v1 Announce Type: new Abstract: Advances in experimental techniques have opened new routes for harnessing non-equilibrium dynamics in mesoscopic quantum systems. In this context, we study the impact of on-site interactions on the transport properties of a continuous quantum thermal machine composed of two coupled oscillators connected to two thermal reservoirs. In the weak system-reservoir coupling regime, where a long-standing debate concerns which reduced description should be preferred, we first show that the Redfield master equation (RME) provides an accurate and unifying framework that interpolates between two well-known limits: the local and global master equations. By relying on the Hierarchy of Pure States (HOPS), a numerically exact stochastic method, we then explore the full parameter space and show that interactions can be leveraged to tune the efficiency of the thermal machine at high temperatures (while leaving it essentially unchanged at low temperatures), induce non-reciprocal transport under asymmetric reservoir couplings, and generate steady-state entanglement within the junction. We derive expressions for system-bath correlators, such as heat and particle currents, consistently across different frameworks. Our work features on-site interactions to enhance the versatility of quantum thermodynamic junctions and clarifies the role of non-Markovianity and non-linearities in quantum transport.

07.
PLOS Computational Biology 2026-06-15

A multilevel hierarchical framework for quantification of experimental heterogeneity in population snapshot data

by David J. Warne, Xiangrun Zhu, Thomas P. Steele, Stuart T. Johnston, Scott A. Sisson, Matthew Faria, Ryan J. Murphy, Alexander P. Browning Biological systems exhibit substantial heterogeneity: that is, variation in specific characteristics of individuals within a population. As a result, it is of critical importance to appropriately account for biological heterogeneity when calibrating mathematical models to infer cellular processes and predict behaviour. Recent approaches consider ordinary differential equations with random parameters to quantify heterogeneity in dynamical processes of cells. In this setting, statistical inference is performed to characterise the distribution of these random parameters within a cell population. One significant limitation of this approach is the tacit assumption that there are no substantial deviations in these distributions across experimental replicates. In this work, we propose a flexible Bayesian hierarchical differential equation modelling framework that quantifies and distinguishes both inter-experimental heterogeneity (heterogeneity between experimental replicates) and intra-experimental heterogeneity (biological heterogeneity within replicate populations). We consider two recent studies that employ mathematical models to interpret flow cytometry snap-shot data and quantify heterogeneity in nano-particle cell interactions and cell internalisation processes. Using simulation data, we demonstrate that substantial inaccuracy in the inferred dynamics can arise when experimental heterogeneity is not accounted for. By contrast, our hierarchical approach is robust to variability in inter-experimental and intra-experimental heterogeneity and our method simplifies to previous methods when inter-experimental heterogeneity is negligible. Our approach is flexible and widely applicable to applications involving replicate populations and snapshot data. We provide open-source implementations of our methods on GitHub.

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

Multi-agent rendezvous in fluid flows via reinforcement learning

arXiv:2606.11274v1 Announce Type: cross Abstract: Rendezvous is a critical task for multi-agent systems, requiring agents to coordinate to meet at an unspecified location. However, achieving this in fluid environments presents a challenge, as it remains unclear how agents can exploit underlying fluid kinematics to facilitate convergence. In this study, we adopt a multi-agent reinforcement learning (MARL) approach to develop physics-informed rendezvous strategies in vortical flows. Compared to a naive strategy, where agents navigate toward their counterparts, MARL strategies significantly improve the rendezvous rate. MARL strategies also show transferability across varying vortex intensities, vortex scales, and swarm sizes. By breaking the symmetry of the state-action map, MARL strategy leverages a non-intuitive mechanism that prevents agents from becoming trapped in separate vortices, thereby enhancing rendezvous success. Additionally, a heuristic strategy is extracted from the learned strategy and also outperforms the naive strategy. Furthermore, a theoretical analysis demonstrates that fluid deformation impedes the rendezvous process. Large finite-time Lyapunov exponents identify where fluid effects separate adjacent agents, suggesting that targets should be planned in weak-deformation regions. Our findings reveal the important role that agent-fluid interactions play in multi-agent tasks and highlight the MARL capability to explore swarm intelligence in complex flow environments.

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

Detecting undisclosed LLM-generated content in parliamentary texts

In this paper, we evaluate the extent of undisclosed LLM-generated content in texts from the parliaments of the United Kingdom and Sweden. In many areas, such as in journalism or in academic writing, there are often requirements to clearly disclose whether AI tools, such as LLMs, have been used. In the case of parliamentary texts, the guidelines on disclosure of AI use are more vague. However, in order to maintain transparency and retain public trust, it is generally recommended that parliamentarians should state whether or not they have used AI when writing texts, such as parliamentary motions. Here, we train an interpretable (glass-box) text classifier using pre-LLM parliamentary texts and LLM-generated versions of such texts. We then apply the classifier to a test set containing recent parliamentary texts, finding a steady increase in undisclosed LLM use, in both parliaments, from 2022 onwards.

10.
arXiv (CS.CV) 2026-06-15

WAM4D: Fast 4D World Action Model via Spatial Register Tokens

World action models (WAMs) have recently shown promise in jointly modeling future observations and executable robot actions. However, most existing WAMs still operate in 2D video or latent spaces, where visually plausible rollouts miss the 3D spatial constraints and occluded contact geometry required for precise manipulation. While geometric foundation models offer strong priors for recovering dense 3D structure and motion from visual observations, forcing WAMs to predict the dense 4D representation introduces costly geometric decoding and slows down causal action generation. To address the trade-off, we present WAM4D, a fast 4D world action model that uses lightweight spatial register tokens as training-time future-depth readouts to transfer pretrained geometric priors into a causal video-action transformer, then removes the register branch for lightweight action inference. To prevent non-causal shortcuts, we further design causal mixture attention for the Mixture-of-Transformers (MoT) WAM backbone, defining modality-specific visibility among video, action, and geometry tokens. Comprehensive experiments on RoboTwin 2.0 and challenging real-world manipulation tasks show that WAM4D improves spatial consistency and achieves competitive action prediction while maintaining efficient inference.

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

Diffusion-Proof: Recipe for Formal Theorem Proving Beyond Auto-Regressive Generation

arXiv:2606.19315v1 Announce Type: new Abstract: Enhancing the formal math reasoning capabilities of Large Language Models (LLMs) has become a key focus in both mathematical and computer science communities in recent years. While significant progress has been made in using state-of-the-art Auto-Regressive (AR) LLMs for formal theorem proving, these models suffer from inherent limitations. Their next-token prediction generation methods may yield suboptimal performance due to the challenges of long-range coherence and the compounding of errors over long sequences. Recent advancements in diffusion LLMs (dLLMs), which generate text through iterative denoising of a multi-token block, offer a promising alternative. However, the application of dLLMs to formal mathematics, where maintaining long-range coherence is critical, remains largely understudied. To address the challenges above, we propose **Diffusion-Proof**, to the best of our knowledge, the first framework to train and apply dLLMs for formal theorem proving. Our frameworks contain training and inference methods for two models. The first one is *dLLM-Prover-7B*, which performs whole-proof writing with long-range coherent tactic usage. The second one is *dLLM-Corrector-7B*, which is a novel large block diffusion-based correction model. It leverages the in-filling capabilities of dLLMs to perform local proof correction using bi-directional information. Extensive experiments demonstrate that **Diffusion-Proof** relatively significantly outperforms the AR LLM baseline trained under the same dataset. **Diffusion-Proof** achieves an absolute improvement of **1.61%** on ProofNet-Test and **6.14%** on MiniF2F-Test benchmarks compare to the baseline. Notably, **Diffusion-Proof** successfully resolves one IMO problem that more advanced thinking model DeepSeek-Prover-V2-7B could not solve, showcasing the unique advantage of dLLMs in formal theorem proving.

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

SorryDB: Can AI Provers Complete Real-World Lean Theorems?

arXiv:2603.02668v2 Announce Type: replace Abstract: We present SorryDB, a dynamically-updating benchmark of open Lean tasks drawn from 78 real world formalization projects on GitHub. Unlike existing static benchmarks, often composed of competition problems, hillclimbing the SorryDB benchmark will yield tools that are aligned to the community needs, more usable by mathematicians, and more capable of understanding complex dependencies. Moreover, by providing a continuously updated stream of tasks, SorryDB mitigates test-set contamination and offers a robust metric for an agent's ability to contribute to novel formal mathematics projects. We evaluate a collection of approaches, including generalist large language models, agentic approaches, and specialized symbolic provers, over a selected snapshot of 1000 tasks from SorryDB. We show that current approaches are complementary: even though an agentic approach based on Gemini Flash is the most performant, it is not strictly better than other off-the-shelf large-language models, specialized provers, or even a curated list of Lean tactics.

13.
arXiv (CS.AI) 2026-06-16

Adaptive inference and function vectors in deep transformers

arXiv:2606.16694v1 Announce Type: cross Abstract: Transformers are widely used as a general-purpose substrate for learning complex correlations between a large collection of coupled variables, but their internal mechanisms have remained mysterious. We introduce a theory of a deep transformer as a mean-field interacting system that implements distributed inference, subject to constraints on communication, locality and depth. We show that such a system can exploit internal state representations ('function vectors') to infer a latent context variable at increasingly finer scales over its layers. In an in-context regression task, the theory predicts a non-trivial relationship between non-Gaussian, hierarchical structure in the latent context variable, and transformer depth. Predictions are tested using constrained linear attention transformers and demonstrate adaptive inference in deep architectures. Feedforward blocks and depth enable transformers to implement a much richer class of in-context learning algorithms than previously described.

14.
arXiv (CS.CV) 2026-06-16

RQUL-UIE: Revitalizing Quality-Unstable Labels for Underwater Image Enhancement via In-Dataset Self-Supervision

Underwater Image Enhancement (UIE) is essential for mitigating degradations caused by water medium. Although learning-based methods have advanced significantly, most rely on paired datasets with unstable label quality, which bottlenecks model performance. This paper proposes a diffusion-based, in-dataset self-supervised learning strategy designed to exploit the quality distribution of training labels. Specifically, we evaluate label quality via semantic perception embeddings from a pre-trained diffusion model in a training-free manner. These quality scores are subsequently quantized into noise-level indices, guiding a multi-step denoising process for level-wise supervision. This mechanism prevents low-quality labels from degrading the model while maximizing their utility during training. Furthermore, a Fourier-based refinement network is incorporated to explicitly reconstruct high-frequency components. Extensive evaluations demonstrate that our method consistently outperforms SOTA approaches in restoration quality. The code and pre-trained model will be available once accepted in link.

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

Nemotron 3 Ultra: Open, Efficient Mixture-of-Experts Hybrid Mamba-Transformer Model for Agentic Reasoning

We introduce Nemotron 3 Ultra, a 550 billion total and 55 billion active parameter Mixture-of-Experts Hybrid Mamba-Attention language model. We pre-trained Nemotron 3 Ultra on 20 trillion text tokens, then extended the context length to 1M tokens, and post-trained using Supervised Fine Tuning (SFT), Reinforcement Learning (RL), and Multi-teacher On-Policy Distillation (MOPD). Nemotron 3 Ultra is our most capable model yet, employing multiple key technologies - LatentMoE, Multi Token Prediction (MTP), NVFP4 pre-training, multi-environment RLVR, MOPD, and reasoning budget control. Nemotron 3 Ultra achieves up to ~6x higher inference throughput as compared to state-of-the-art publicly available LLMs while attaining on-par accuracy. The state-of-the-art accuracy, high inference throughput, and 1M token context length make Nemotron 3 Ultra ideal for long-running autonomous agentic tasks. We open-source the base, post-trained, and quantized checkpoints, along with the training data and recipe on HuggingFace.

17.
arXiv (CS.AI) 2026-06-19

One Probe Won't Catch Them All: Towards Targeted Deception Detection

arXiv:2602.01425v2 Announce Type: replace Abstract: Linear probes are a promising approach for monitoring AI systems for deceptive behaviour. Previous work has shown that a linear classifier trained on a contrastive instruction pair and a simple dataset can achieve good performance. However, these probes exhibit notable failures even in straightforward scenarios, including spurious correlations and false positives on non-deceptive responses. In this paper, we demonstrate that deception detection is inherently heterogeneous: while a single universal probe achieves modest improvements (+0.032 AUC), post-hoc oracle analysis reveals substantially higher potential (+0.108 AUC) when probes are matched to specific deception types, and synthetic validation experiments suggest this ceiling is achievable a priori when the deception type is known in advance. Our findings reveal that instruction pairs capture deceptive intent rather than content-specific patterns, explaining why prompt choice dominates probe performance (70.6% of variance). Given this heterogeneity, we conclude that organizations should define their specific threat models and deploy appropriately matched probes rather than seeking a universal deception detector.

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

Sequential Hiring of Contingent Workers Through Learning-Based Optimization

arXiv:2606.18438v1 Announce Type: cross Abstract: In this paper, we study a sequential workforce management problem in a contingent labor setting with uncertainty in both worker production and labor supply. A firm seeks to maximize cumulative profit by maintaining an active team of fixed size while learning worker productivity over time. We emphasize two critical operational frictions in this problem: replacing workers is costly, and workers may not be available immediately for hiring because of, for example, prior job commitments, scheduling constraints, or onboarding procedures. Thus, hiring decisions take effect only after a random delay. We formulate this problem as a stochastic multi-play bandit with costly switching and delayed actions, and develop a learning-based hiring policy, DR-UCB (DelayedReplacement-UCB), that makes replacement and hiring decisions sequentially through learning cycles. In each cycle, the policy uses real-time production data to determine when to initiate workforce changes and which workers to replace and hire. We show that the leading-order regret of the proposed policy matches its lower bound in its dependence on the time horizon. Our numerical experiments show that DR-UCB outperforms benchmark policies.

19.
arXiv (CS.AI) 2026-06-12

CloudCons: A Comprehensive End-to-End Benchmark for Cloud Resource Consolidation

arXiv:2606.13513v1 Announce Type: new Abstract: Driven by conservative over-provisioning to guarantee service reliability, resource utilization in cloud data centers remains at low levels. To mitigate this, the forecast-then-optimize paradigm has emerged to optimize consolidation by anticipating future demands. While emerging time series foundation models promise to enhance this paradigm through zero-shot generalization, existing benchmarks focus solely on prediction error metrics. The actual decision utility of these advanced models remains unverified, rendering their practical value for downstream tasks uncertain. To bridge this gap, we propose CloudCons, a comprehensive end-to-end benchmark designed to evaluate forecasting models within the specific context of cloud resource consolidation. We build high-quality datasets that cover diverse workloads from Huawei Cloud, Microsoft Azure, and Google Borg, capturing distinct service characteristics ranging from synchronized diurnal rhythms to stochastic, pulse-like bursts and high-frequency noise. We conduct an extensive evaluation of statistical, deep learning, and foundation models. Our experiments reveal a pivotal finding: while foundation models demonstrate superior zero-shot forecasting accuracy, this advantage does not inherently translate into better decision utility. Of practical significance, we systematically analyze how the selection of predictive quantiles acts as a critical lever. We provide actionable guidelines for calibrating these selections to balance the trade-off between resource efficiency and service reliability, offering vital insights for real-world deployment decisions.

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

Generalized Schrödinger Bridge on Graphs

arXiv:2602.04675v2 Announce Type: replace Abstract: Transportation on graphs is a fundamental challenge across many domains, where decisions must respect topological and operational constraints. Despite the need for actionable policies, existing graph-transport methods lack this expressivity. They rely on restrictive assumptions, fail to generalize across sparse topologies, and scale poorly with graph size and time horizon. To address these issues, we introduce Generalized Schrödinger Bridge on Graphs (GSBoG), a novel scalable data-driven framework for learning executable controlled continuous-time Markov chain (CTMC) policies on arbitrary graphs under state cost augmented dynamics. Notably, GSBoG learns trajectory-level policies, avoiding dense global solvers and thereby enhancing scalability. This is achieved via a likelihood optimization approach, satisfying the endpoint marginals, while simultaneously optimizing intermediate behavior under state-dependent running costs. Extensive experimentation on challenging real-world graph topologies shows that GSBoG reliably learns accurate, topology-respecting policies while optimizing application-specific intermediate state costs, highlighting its broad applicability and paving new avenues for cost-aware dynamical transport on general graphs.

21.
arXiv (CS.CL) 2026-06-17

findsylls: A Language-Agnostic Toolkit for Syllable-Level Speech Tokenization and Embedding

Syllable-level units offer compact and linguistically meaningful representations for spoken language modeling and unsupervised word discovery, but research on syllabification remains fragmented across disparate implementations, datasets, and evaluation protocols. We introduce findsylls, a modular, language-agnostic toolkit that unifies classical syllable detectors and end-to-end syllabifiers under a common interface for syllable segmentation, embedding extraction, and multi-granular evaluation. The toolkit implements and standardizes widely used methods (e.g., Sylber, VG-HuBERT) and allows their components to be recombined, enabling controlled comparisons of representations, algorithms, and token rates. We demonstrate findsylls on English and Spanish corpora and on new hand-annotated data from Kono, an underdocumented Central Mande language, illustrating how a single framework can support reproducible syllable-level experiments across both high-resource and under-resourced settings.

22.
arXiv (CS.CL) 2026-06-16

Benchmarking LLM Agents on Meta-Analysis Articles from Nature Portfolio

Meta-analysis is a demanding form of evidence synthesis that combines literature retrieval, PI/ECO-guided study selection, and statistical aggregation. Its structured, verifiable workflow makes it an ideal substrate for evaluating systematic scientific reasoning, yet existing benchmarks lack ground truth across the full retrieval-screening-synthesis pipeline. We introduce MetaSyn, a dataset of 442 expert-curated meta-analyses from Nature Portfolio journals. Each entry pairs a research question with PI/ECO criteria, a retrieval corpus of 140k PubMed articles, verified positive studies, hard negatives that are topically similar but PI/ECO-ineligible, and complete search strategies and date bounds. Benchmarking twelve pipeline configurations (nine RAG variants and a protocol-driven agent) reveals a critical screening bottleneck: despite a retrieval ceiling of 90.9% recall at K=200, no system recovers more than 52.7% of ground-truth included literature. Current LLMs fail to reliably separate eligible studies from PI/ECO-failing distractors in pools of comparable topical relevance. Stage-attributed metrics capture where systems succeed and fail; a single end-to-end score does not.

23.
medRxiv (Medicine) 2026-06-11

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

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

24.
PLOS Computational Biology 2026-06-16

Evolution and the ultimatum game: An agent-based model with interbirth intervals and population structure

by Jeffrey C. Schank, Matt L. Miller The ultimatum game (UG) is widely used to study mutually beneficial exchanges, fairness, and prosocial behavior across different societies. However, human behavior in UG experiments does not align with the game-theoretical prediction that proposers should offer the least positive amount and responders should accept such offers. Instead, proposers make generous offers that are greater than the minimum responders are willing to accept, resulting in generous offers with wide offer-acceptance gaps. Numerous evolutionary models of the UG have been created and studied to explain human behavior, particularly generous offers made in UG experiments. These models have recently faced criticism for lacking biological realism and not adequately explaining the data. Here, we present an agent-based model inspired by our hunter-gatherer ancestors and with a biologically more realistic selection process. We assume that (1) agents exist in group-structured and group-clustered populations, where reproduction (2) depends on resource accumulation, but (3) is limited by interbirth intervals. We ran simulations to assess whether this biologically more realistic model evolves patterns of behavior consistent with patterns in the data from meta-analyses of human behavior in the UG. For the proposed model, we show that generous offers robustly evolve, as well as the difficult-to-explain offer-acceptance gaps, only in group-structured populations with interbirth intervals. We demonstrate that these results are robust and may help explain variation in data across societies. We discuss how interbirth intervals interact with group structure to modulate offer and rejection costs, favoring the evolution of generous offers, offer-acceptance gaps, and other patterns in the data on human behavior in the UG. We also discuss why weak selection and/or high mutation rate models cannot explain all the patterns in UG experimental data. We discuss biological realism and conclude that group structure and interbirth intervals may be essential for explaining prosocial behavior across societies.

25.
arXiv (CS.LG) 2026-06-17

The Morse Transform for Discrete Shape Analysis

arXiv:2503.04507v2 Announce Type: replace-cross Abstract: The geometry of an object plays a vital role in modulating its interactions with the physical world. It nevertheless remains difficult to describe geometric information numerically for the purposes of statistical inference or classification tasks. Here, we introduce a new topological transform which leverages directional piecewise-linear Morse theory to quantify the geometry of an embedded object by cataloguing critical points across multiple height-functions. The output of this Morse transform records both the heights and the local topological type (peak, trough or saddle) of the critical points that characterise the underlying shape, retaining finer information than the Euler characteristic transform whilst naturally prioritising a shape's outermost regions. Crucially, this output can be further compressed into a rich but compact feature vector. We benchmark the Morse feature vector as a descriptor for ligand-based virtual screening (LBVS), which intrinsically depends on the shape of molecules. Under a common gradient-boosted tree classification pipeline, Morse descriptors achieve the highest mean AUROC when compared to other topological transform descriptors and to standard shape-based LBVS descriptors.