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

Direction-Conditioned Policies via Compositional Subgoal Scoring for Online Goal-Conditioned Reinforcement Learning

arXiv:2606.16515v1 Announce Type: cross Abstract: Hamilton-Jacobi-Bellman theory implies that the optimal goal-conditioned action depends on the goal only through the gradient of the goal-reaching distance at the current state, yet standard online GCRL still conditions the actor on the raw goal – a signal that is geometrically uninformative when the goal is far from the data distribution. We propose Direction-Conditioned Policies (DCP), a fully online method that decomposes goal-reaching into two components sharing one InfoNCE representation $\psi$: a subgoal-scoring step that selects a visited state $z_t$ aligned with the final goal $g$ in $\psi_g$, and a direction-conditioned actor that consumes the unit direction $d_t$ and magnitude $r_t$ from $\psi(s_t)$ to $\psi(z_t)$. The two components train jointly, factor cleanly at deployment (subgoal scoring is removed, while direction conditioning remains with $g$ in place of $z_t$), and admit independent modification at the same $(d_t,r_t)$ interface. We prove three results. First, direction sufficiency under HJB: the optimal action under control-affine dynamics depends on the goal only through the value gradient. Second, a quantitative bound showing that, under mild conditions on the learned representation and assuming the scoring rule returns an on-path $z_t$, the actor's conditioning input at training and at deployment coincide up to representation error and geodesic slack. Third, a controllable-subspace characterization of when directional conditioning fails. Across nine environments, DCP improves over Contrastive RL on most final metrics, with the largest gains on manipulation and obstacle-interaction tasks; a qualitative analysis of the learned $\psi$-distance landscape shows the contrastive representation behaves as an online quasimetric encoding environment topology, and the single failure case (AntSoccer) localizes to a learned-gradient pathology that the theory anticipates.

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

State-Grounded Multi-Agent Synthetic Data Generation for Tool-Augmented LLMs

Training tool-augmented LLM agents requires large corpora of multi-turn, tool-grounded conversational data that is expensive to annotate, privacy-constrained in production settings, and largely absent from public datasets. We present StateGen, a synthetic data generation platform that produces scored, reasoning-trace-rich training conversations by orchestrating a four-role LLM loop: a persona-conditioned user simulator, an agent under test, a state-grounded tool simulator, and a multi-axis LLM judge. The key architectural contribution is an authoritative state manager that maintains a structured world-state object across turns, enforcing a backend-is-truth invariant that eliminates the dominant class of tool-call hallucinations by construction. StateGen extends naturally to hierarchical multi-agent settings by declaring sub-agents as tools, all sharing a single state object. We report results on 64,698 evaluated conversations across three production corpora: tool-call hallucination scores reach 9.66/10, the system supports persona-driven variation via a 23-dimensional trait vector, and a cleanly separated train and golden evaluation set split confirms the data is not memorization bait (per-criterion gap analysis). Comparison with eight external systems shows that no single publicly available platform combines multi-turn generation, state-grounded tool simulation, hierarchical multi-agent support, and built-in judge scoring.

03.
bioRxiv (Bioinfo) 2026-06-18

Metrics for Evaluating Biological AI Model Predictive Accuracy at the Data-Substrate Level

作者:

Reports in the biological literature disagree on whether a given model can predict a biological outcome from a given data sample — one study finding a model capable, another, on the same kind of data, finding it is not. This is particularly a challenge in relation to LLMs–where the models are large and opaque, with weights and training data inaccessible.textbf{ }Such disagreements cannot be settled by directly inspecting the model. To address this challenge, we considertextbf{ }an alternative approach: assessing whether the data sample is adequate to support the prediction asserted. For a given dataset, its substrate — the underlying structure of the data — determines what any model can recover, independent of architecture or capacity. At the same time, predicting the present state of a biological process and predicting the direction of its future change are different tasks; the second is supportable among AI models only where the data encode direction as determinable from the state — a property we call encoding — and is unsupportable where the same observed state precedes change in opposite directions — a property we call non-identifiability, in the informational rather than the statistical sense. We introduce two generic metrics, Predictive Blindness Risk (PBR) and Prediction Indeterminacy Measure (PIM), that evaluate a data substrate for predictive accuracy directly — without access to model weights, architecture, or training data — and locate the regions of a data substrate where a predictive claim can be supported and where it cannot. Using human biological subjects, we employ the Yale Brain Metastases Longitudinal Data (1,430 human subjects; 11,892 MRI studies; four sequences) and show that direction of change was non-identifiable across regions encompassing the majority of transitions; a nonlinear AI model gained essentially nothing over majority-direction prediction there while recovering direction near-perfectly where the state encoded it; and model accuracy tracked data-substrate resolvability continuously (Spearman {rho} = -0.95 to -1.00). The metrics adjudicate, before any model is trusted and from the data alone, where claims of predictive accuracy — of state, or of the law of change — can be supported.

04.
arXiv (quant-ph) 2026-06-15

Bandstructure of a coupled BEC-cavity system: effects of dissipation and geometry

arXiv:2504.17730v2 Announce Type: replace-cross Abstract: We present a theoretical model for a transversally driven Bose-Einstein condensate coupled to an optical cavity. We focus on the interplay between different coherent couplings, which can trigger a structural phase transition, known as the superradiant phase transition. Our approach, based on band structure theory and a mean-field description, enables a comprehensive analysis of the nature of the system's excited modes, precursing the phase transitions. By incorporating dissipative couplings, intrinsic to these systems, we find non-Hermitian phenomena such as the coalescence of crossing precursor modes and the emergence of exceptional points (EPs). The general formulation of our model allows us to explain the role of an angle between transverse pump and the cavity deviating from $90^\circ$. This offers us a unified perspective on the plethora of different implementations of such systems.

05.
arXiv (CS.CL) 2026-06-16

MyPCBench: A Benchmark for Personally Intelligent Computer-Use Agents

Current benchmarks for computer-use agents evaluate models in impersonal environments. This leaves a gap between evaluation and deployment where personal assistants are expected to work across a user's whole digital life, including their context, historical data, and logged-in accounts. This gap is widest on web tasks, where live web evaluations cannot exercise sites that require logging in or personal information, the kind of site a real personal assistant has to drive. We introduce MyPCBench, which tests computer-use agents as personal assistants on a Linux desktop populated with 17 simulated real-world web applications and a full desktop stack, all seeded for one canonical persona, Michael Scott from The Office. We define 184 tasks in this environment, each inspired by a real request drawn from the OpenClaw community, and benchmark six closed and open-weight models with a uniform computer+bash tool surface. We find that the best model, Claude Opus 4.6, fully solves 55.4\% of the tasks, the only model above 50\%. Model failures cluster on tasks that span many applications and on long trajectories, where personalization stresses an assistant the most. We release the environment, task set, and agent harness at https://mypcbench.com.

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

Modality-Aware Feature Matching in Visual and Vision-Language Applications: A Comprehensive Survey

Feature matching is a cornerstone task in computer vision, essential for applications such as image retrieval, stereo matching, 3D reconstruction, and SLAM. This survey comprehensively reviews modality-based feature matching, exploring traditional handcrafted methods and emphasizing contemporary deep learning approaches across various modalities, including RGB images, depth images, 3D point clouds, LiDAR scans, medical images, and vision-language interactions. Traditional methods, leveraging detectors like Harris corners and descriptors such as SIFT and ORB, demonstrate robustness under moderate intra-modality variations but struggle with significant modality gaps. Contemporary deep learning-based methods, exemplified by detector-free strategies like CNN-based SuperPoint and transformer-based LoFTR, substantially improve robustness and adaptability across modalities. We highlight modality-aware advancements, such as geometric and depth-specific descriptors for depth images, sparse and dense learning methods for 3D point clouds, attention-enhanced neural networks for LiDAR scans, and specialized solutions like the MIND descriptor for complex medical image matching. Cross-modal applications, particularly in medical image registration and vision-language tasks, underscore the evolution of feature matching to handle increasingly diverse data interactions.

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

IAPO: Input Attribution-Aware Policy Optimization for Tool Use in Small Multimodal Agents

arXiv:2606.11652v1 Announce Type: new Abstract: This paper investigates reinforcement learning (RL) methods for improving tool-calling capabilities in multimodal small language model (SLM) agents. While existing works have explored various reward designs to improve agentic tool-calling ability, these approaches face inherent limitations for SLM training, especially under multimodal scenarios. First, many existing methods evaluate tool use correctness through exact matching against certain ground-truth or predefined formats. However, this assumption is often unsuitable for multimodal tasks, where multiple tool use paths may be valid and annotated tool trajectories are typically unavailable. Second, such sparse and brittle binary rewards provide little guidance on how to improve the underlying decision process, making them particularly difficult for multimodal SLM to learn from. To address these issues, we propose Input Attribution-Aware Policy Optimization (IAPO), an RL algorithm for improving tool use in multimodal SLM by aligning the model's attribution across input components with that of a stronger teacher. Experiments on Qwen2.5-VL-3B show that the proposed method improves visual question answering accuracy by an average of 3% across six test sets compared with existing visual tool use work, by helping the model attend to the most relevant input evidence.

09.
medRxiv (Medicine) 2026-06-15

Using wastewater surveillance to explore community-level dietary intake in sewered and non-sewered sanitation systems in Malawi, Africa

Wastewater can be used to measure biomarkers that reflect population-level dietary intake and diversity; however, how this approach may apply in a low-income country remains a knowledge gap. This study aims to evaluate whether select dietary-related metabolites can be detected in wastewater and environmental surveillance (WES) samples from both sewered and non-sewered sanitation systems in Malawi, Africa. Fourteen WES samples were collected and analyzed from two university campuses in Mzuzu and Thyolo, Malawi. Four targets were analyzed: N-methyl-2-pyridone-5-carboxamide (2PY; a biomarker of vitamin B3), 4-pyridoxic acid (4-PA; a biomarker of vitamin B6), as well as enterodiol and enterolactone (biomarkers of dietary fiber and polyphenol consumption). An 18-question survey, paired spatiotemporally with the WES measurements, assessed self-reported daily dietary intake, food insecurity, and nutrient deficiency symptoms among 500 respondents. Among the 14 WES samples, 2PY, 4-PA, and enterolactone were detected, while enterodiol was not detected above the method limit (

10.
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.

11.
medRxiv (Medicine) 2026-06-18

Evaluating Deep-Learning Based Quantification of Breast Arterial Calcification on Mammography for Cardiovascular Risk Assessment

Purpose: To develop and evaluate a deep learning model for automated quantification of breast arterial calcification (BAC) on screening mammography and to assess whether AI-derived BAC burden predicts major adverse cardiovascular events (MACE) in women. Methods: In this retrospective study, 202,006 women who underwent screening mammography without history of MACE were included. A BAC segmentation model was trained on an expert-annotated dataset using a multi-task U-Net with a ResNet-18 encoder to detect and segment BAC. BAC burden was quantified as area (mm{superscript 2}) from model-generated masks using DICOM pixel spacing and categorized by tertiles into low, intermediate, and high. The PREVENT score and incident MACE were identified from electronic health records. Cox proportional hazards models were developed to evaluate AI-derived BAC burden and PREVENT score alone, and combined models for 5 - and 10-year cardiovascular risk prediction. Results: Among 202,006 women (mean age 54.8{+/-}11.7 years), 23.1% had AI-detected BAC, and 7,701 (3.8%) developed incident MACE during a median follow - up of 7.5 years. On the geographically held-out test set, the BAC model achieved an AUROC of 0.97, Dice score of 0.6678, and Pearson correlation of 0.961 between AI-derived and manually annotated BAC burden. BAC burden increased with age and was higher among women who developed MACE. Five - year MACE incidence increased across BAC categories from 1.5% in women without BAC to 6.9% in those with high BAC burden. BAC burden alone showed modest prediction of MACE, with 5-year and 10-year AUROCs of 0.661 and 0.650, respectively, while PREVENT achieved AUROCs of 0.781 and 0.771. Adding BAC to PREVENT produced minimal improvement in discrimination. Conclusion: Deep learning-based BAC quantification from routine mammography is feasible, accurate, and associated with future cardiovascular risk. Although BAC added little to PREVENT for overall discrimination, it may serve as a scalable opportunistic imaging biomarker to identify women at elevated cardiovascular risk and support preventive care.

12.
PLOS Computational Biology 2026-06-22

Beyond the canonical: The role of post-transcriptional regulation in drug-target interaction prediction

by Md Istiaq Ansari, Khandakar Tanvir Ahmed, Debby D. Wang, Kirill Medvedev, Wei Zhang Protein isoforms produced from the same gene through post-transcriptional regulatory mechanisms, such as alternative splicing, can substantially alter protein structure and function, including drug-binding properties. However, most existing drug-target interaction (DTI) and drug-target affinity (DTA) prediction models rely exclusively on a single representative protein sequence per gene, typically the canonical or longest isoform, thereby overlooking the functional diversity introduced by alternative isoforms. This assumption can introduce bias, limit generalizability, and compromise the biological validity of model predictions. In this study, we systematically investigate the impact of protein isoform variation on DTI prediction accuracy. Our results show that substituting the canonical sequence with an alternative isoform often leads to substantial declines in predictive performance. Structural and binding affinity analyses further reveal that these discrepancies are frequently associated with changes in predicted binding-site configurations, which we further examine through controlled perturbations of binding-site residues. These experiments suggest that even subtle alterations in binding regions can lead to inconsistent DTI predictions. Overall, our findings uncover a critical limitation in current DTI modeling frameworks and underscore the importance of incorporating isoform-specific information to better reflect biological reality and improve therapeutic relevance. The codes and datasets are available at https://github.com/compbiolabucf/DTIVariant.

13.
medRxiv (Medicine) 2026-06-15

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

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

14.
arXiv (CS.CV) 2026-06-17

SCC-Loc: A Unified Semantic Cascade Consensus Framework for UAV Thermal Geo-Localization

Cross-modal Thermal Geo-localization (TG) provides a robust, all-weather solution for Unmanned Aerial Vehicles (UAVs) in Global Navigation Satellite System (GNSS)-denied environments. However, profound thermal-visible modality gaps introduce severe feature ambiguity, systematically corrupting conventional coarse-to-fine registration. To dismantle this bottleneck, we propose SCC-Loc, a unified Semantic-Cascade-Consensus localization framework. By sharing a single DINOv2 backbone across global retrieval and MINIMA$_{RoMa}$ matching, it minimizes memory footprint and achieves zero-shot, highly accurate absolute position estimation. Specifically, we tackle modality ambiguity by introducing three cohesive components. First, we design the Semantic-Guided Viewport Alignment (SGVA) module to adaptively optimize satellite crop regions, effectively correcting initial spatial deviations. Second, we develop the Cascaded Spatial-Adaptive Texture-Structure Filtering (C-SATSF) mechanism to explicitly enforce geometric consistency, thereby eradicating dense cross-modal outliers. Finally, we propose the Consensus-Driven Reliability-Aware Position Selection (CD-RAPS) strategy to derive the optimal solution through a synergy of physically constrained pose optimization. To address data scarcity, we construct Thermal-UAV, a comprehensive dataset providing 11,890 diverse thermal queries referenced against a large-scale satellite ortho-photo and corresponding spatially aligned Digital Surface Model (DSM). Extensive experiments demonstrate that SCC-Loc establishes a new state-of-the-art, suppressing the mean localization error to 9.37 m and providing a 7.6-fold accuracy improvement within a strict 5-m threshold over the strongest baseline. Code and dataset are available at https://github.com/FloralHercules/SCC-Loc.

15.
arXiv (CS.CL) 2026-06-18

Redact or Keep? A Fully Local AI Cascade for Educational Dialogue De-Identification

Educational dialogue is a valuable but sensitive resource for research: the same transcripts that capture authentic learning often capture personally identifiable information (PII) entangled with curricular content, where "Riemann" may refer to a real student or to a mathematical concept. Existing approaches force a tradeoff between governance and accuracy. Commercial Large Language Models (LLMs) can handle this ambiguity but require sending student data to third parties, while local named entity recognition (NER) systems preserve governance but over-redact curricular terms. We propose a fully local cascade framework that reframes de-identification from open-ended entity recognition to constrained privacy triage. A recall-first union proposer combines two lightweight encoders with deterministic rules to over-generate candidate spans; a context-aware reviewer then makes a binary Redact/Keep decision for each candidate using surrounding dialogue and speaker role. We evaluate three reviewer configurations against same-family LLM-only baselines and a commercial API on math tutoring transcripts from two large platforms. The strongest local configuration reaches 0.958 macro F1, compared with 0.767 for a same-family LLM-only baseline and 0.706 for the commercial API, while running entirely on a single laptop. On a targeted challenge set of curricular-personal name ambiguity, the same configuration degrades by only 0.03 F1 versus 0.19 to 0.25 for smaller reviewers. These results suggest that for educational de-identification, problem formulation matters more than model scale.

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

GAGPO: Generalized Advantage Grouped Policy Optimization

arXiv:2605.13217v1 Announce Type: cross Abstract: Reinforcement learning has become a powerful paradigm for post-training large language model agents, yet credit assignment in multi-turn environments remains a challenge. Agents often receive sparse, trajectory-level rewards only at the end of an episode, making it difficult to determine which intermediate actions contributed to success or failure. As a result, propagating delayed outcomes back to individual decision steps without relying on costly auxiliary value models remains an open problem. We propose Generalized Advantage Grouped Policy Optimization (GAGPO), a critic-free reinforcement learning method for precise, step-aligned temporal credit assignment. GAGPO constructs a non-parametric grouped value proxy from sampled rollouts and uses it to compute TD/GAE-style temporal advantages, recursively propagating outcome supervision backward through time. Combined with group-wise advantage normalization and an action-level importance ratio, GAGPO extracts stable, localized optimization signals directly from multi-turn trajectories. Experiments on ALFWorld and WebShop show that GAGPO outperforms strong reinforcement learning baselines. Further analyses demonstrate faster early-stage learning, improved interaction efficiency, and smoother optimization dynamics, suggesting that GAGPO offers a simple yet effective framework for multi-turn agentic reinforcement learning.

17.
PLOS Computational Biology 2026-06-09

Multi-stable oscillations in cortical networks with two classes of inhibition

by Arnab Dey Sarkar, Bard Ermentrout In the classical view of cortical rhythms, interactions between excitatory pyramidal neurons (E) and inhibitory parvalbumin-expressing interneurons (I) are sufficient to generate gamma- and beta-band oscillations. However, it is now well established that multiple inhibitory interneuron subtypes exist and that they play important roles in the generation and modulation of these rhythms. In this paper, we develop a spiking network model consisting of populations of E, I, and an additional interneuron type, somatostatin-expressing neurons (S), which receive excitation from the E cells and inhibit both the E and I populations. The S cells are further modulated by a third inhibitory subtype, vasoactive intestinal peptide (VIP) neurons, which receive inputs from other cortical areas. We reduce the spiking network to a system of nine differential equations that describe the mean membrane potential, firing rate, and synaptic conductance for each population. Using this reduced model, we identify a wide range of parameters that exhibit multiple coexisting rhythms. Employing tools from nonlinear dynamics, we then explore the roles of the two classes of inhibition, as well as VIP modulation, in shaping the properties of these rhythms.

18.
arXiv (quant-ph) 2026-06-15

Extensible Fluxonium Architecture Using Tunable Couplers with Low Shunt Capacitance

arXiv:2606.01647v2 Announce Type: replace Abstract: Fluxonium qubits have demonstrated high-fidelity operations and long coherence times in small-scale systems, highlighting their promise for quantum computing. However, large-scale integration into a high-performance two-dimensional (2D) qubit array remains the central challenge for practical applications. In this work, we introduce an extensible architecture for scaling up fluxonium qubits in 2D grids. To address the key challenges, namely achieving controllable strong interaction and high connectivity for qubits featuring small shunting capacitors (footprints), we propose using low-shunt-capacitance couplers to enable tunable interactions between fluxonium qubits. When embedded into 2D square lattices, large couplings can be achieved even with relatively small coupling capacitances, thus enabling multiple connections with sufficient capacitance budget. We further propose coupler realizations based on generalized flux qubit circuits, specifically the quarton and the fluxonium, and demonstrate that both enable fast, high-fidelity gates with low spectator errors, while supporting multiple connections on 2D grids.

19.
arXiv (math.PR) 2026-06-17

Order statistics for edge eigenvectors of Wigner matrices

arXiv:2606.17425v1 Announce Type: new Abstract: In this paper, we establish a general comparison theorem for the order statistics of the edge eigenvectors for generalized Wigner matrices. Consequently, we derive the Gumbel law for the maximal edge eigenvector component and prove the universality of the Gaussian fluctuations of the order statistics in an intermediate regime close to the maximum. In addition, our comparison result also implies a quantitative first order estimate for moderately small order statistics.

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

Reinforcement Learning for LLM-based Event Forecasting

arXiv:2606.15917v1 Announce Type: new Abstract: We use Group Relative Policy Optimization (GRPO), a recently devised sample and memory efficient reinforcement learning method, to finetune pretrained LLMs in the range of 1.5B to 14B parameters equipped with the ability to get current information through the use of a Wikipedia revisions tool, or news summaries, to forecast real events beyond the knowledge cutoff of the LLM, as well as problems made to simulate different aspects of the dynamics of that training. We use the results of these experiments to comment on the scaling capability of LLMs for forecasting, as well as classify how judgmental forecasting fits into the verifiable/unverifiable domain taxonomy, considering the impact of the inherent aleatoric uncertainty when forecasting future events (e.g. the roll of a die). As a result of the GRPO training, we manage to bring a 1.5B parameter transformer (Qwen 2.5 1.5B) to forecasting performance superior to Claude Sonnet 3.5 over the same dataset as measured by cross entropy from the market agreed probabilities. We also discuss various dead ends on the path to this result.

22.
PLOS Computational Biology 2026-06-17

Machine learning-driven identification of virulence determinants in <i>Borrelia burgdorferi</i> associated with human dissemination

by Hoa Thanh Nguyen, Catherine A. Brissette Lyme disease, the most common tick-borne infectious disease in the United States, presents with highly variable clinical outcomes, ranging from localized erythema migrans to severe disseminated complications affecting the heart, joints, and nervous system. The bacterial determinants underlying this phenotypic variation remain largely unknown, limiting our ability to predict disease progression and optimize treatment strategies. Here, we applied machine learning (ML) approaches to identify specific amino acid residues within surface-exposed virulence factors that predict human dissemination phenotypes. Utilizing the published whole genome sequences from 299 clinical Borrelia burgdorferi isolates collected from the United States and Slovenia over a 30-year period (1992–2021), we extracted and characterized translated amino acid sequences (variants) of seven known virulence factors (BB_0406, BBK32, DbpA, OspA, OspC, P66, and RevA). Protein variants were classified based on their association with disseminated versus localized infections using clinical metadata. Cramér’s V analysis revealed possible strong associations between dissemination phenotypes and five adhesins: BBK32, DbpA, OspC, P66, and RevA. We developed ML models using five algorithms with multiple feature selection strategies, achieving robust predictive performance for DbpA, OspC, and RevA variants (all performance metrics > 0.7). Feature importance analysis identified 57, 29, and 42 key predictive residues for DbpA, OspC, and RevA, respectively. Notably, B-cell epitope prediction revealed significant enrichment of ML-identified residues within predicted epitope regions for OspC (11 overlapping residues, OR = 3.57, p = 0.006) and RevA (12 overlapping residues, OR = 2.37, p = 0.048), suggesting these residues may influence immune recognition and bacterial persistence. This study establishes the first computational framework linking Borrelia protein sequence variants to clinical dissemination phenotypes, providing molecular insights into Lyme disease pathogenesis that may inform the development of improved diagnostics and therapeutic targets.

24.
arXiv (CS.CV) 2026-06-11

From Correspondence to Actions: Human-Like Multi-Image Spatial Reasoning in Multi-modal Large Language Models

While multimodal large language models (MLLMs) have made substantial progress in single-image spatial reasoning, multi-image spatial reasoning, which requires integration of information from multiple viewpoints, remains challenging. Cognitive studies suggest that humans address such tasks through two mechanisms: cross-view correspondence, which identifies regions across different views that correspond to the same physical locations, and stepwise viewpoint transformation, which composes relative viewpoint changes sequentially. However, existing studies incorporate these mechanisms only partially and often implicitly, without explicit supervision for both. We propose Human-Aware Training for Cross-view correspondence and viewpoint cHange (HATCH), a training framework with two complementary objectives: (1) Patch-Level Spatial Alignment, which encourages patch representations to align across views for spatially corresponding regions, and (2) Action-then-Answer Reasoning, which requires the model to generate explicit viewpoint transition actions before predicting the final answer. Experiments on three benchmarks demonstrate that HATCH consistently outperforms baselines of comparable size by a clear margin and achieves competitive results against much larger models, while preserving single-image reasoning capabilities.

25.
medRxiv (Medicine) 2026-06-16

Adherence to Red Reflex and Vision Screening Recommendations: A Deep Dive into Primary Care Implementation Gaps

Introduction: Early childhood vision screening is critical for detecting amblyopia and other vision-threatening conditions. Despite screening recommendations during well-child visits, rates remain low. Red reflex assessment is recommended to identify serious ocular pathology, yet its use in primary care is not well described. We examined rates and drivers of vision screening in pediatric primary care. Methods: We conducted a retrospective review of electronic health records for children 3 to 5 years attending well-child visits in 2022 in one of three representative primary care clinics within a university health system. Outcomes were documented red reflex and functional vision tests. We evaluated associations with patient demographics and clinic site using multivariable logistic regression Results: Among 1,003 visits, 21.1% (n=212) had a documented red reflex assessment, and 60.8% (n=610) a functional vision test. Younger children (ages 3 and 4 vs. 5 years) had higher odds of red reflex assessment [adjusted odds ratio (aOR) 9.00 and 8.64], and lower odds of a functional vision (aOR 0.47 and 0.59) test. Females had higher odds of red reflex assessment (aOR 1.53). Other/Multiracial children had lower odds of red reflex assessment than Non-Hispanic White children (aOR 0.48). Screening rates varied significantly by clinic site Conclusions: Visual function and red reflex assessment are inconsistently performed in pediatric primary care, with particularly low rates of red reflex documentation. Screening rates varied between clinics and were affected by age. These findings highlight missed opportunities for early detection of vision-threatening conditions and identify targets for improving adherence to pediatric vision screening recommendations