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

Context-Driven Incremental Compression for Multi-Turn Dialogue Generation

Modern conversational agents condition on an ever-growing dialogue history at each turn, incurring redundant attention and encoding costs that grow with conversation length. Naive truncation or summarization degrades fidelity, while existing context compressors lack cross-turn memory sharing or revision, causing information loss and compounding errors in long dialogues. We revisit the context compression under conversational dynamics and empirically present its fragility. To improve both efficiency and robustness, we introduce Context-Driven Incremental Compression (C-DIC), which treats a conversation as interleaved contextual threads and stores revisable per-thread compression states in a single, compact dialogue memory. At each turn, a lightweight retrieve, revise, and write-back loop shares information across turns and updates stale memories, stabilizing long-horizon behavior. In addition, we adapt truncated backpropagation-through-time (TBPTT) to our multi-turn setting, learning cross-turn dependencies without full-history backpropagation. Extensive experiments on long-form dialogue benchmarks demonstrate superior performance and efficiency of C-DIC; notably, C-DIC shows stable inference latency and perplexity over hundreds of dialogue turns, supporting a scalable path to high-quality dialogue modeling.

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

Computational Identifiability

arXiv:2606.19361v1 Announce Type: cross Abstract: Identification conditions describe the computability of a target query or parameter of interest as a function of the type and amount of information available. In causal identification, this information is often expressed in the form of a causal graph, and data are observed or collected for some subset of variables in the graph. Target queries may be for a single effect alone or for a class of effects in a given model. The derivation of an identification algorithm then defines mathematically the process by which the desired causal effect(s) can be uniquely determined, theoretically, in expectation. Identifiability in expectation, or 'theoretical identifiability,' generally assumes asymptotic properties, infinite data, or other mathematically idealized conditions. In this paper, we explore a fundamental distinction between this theoretical, idealized notion of identifiability and a proposed alternative that is computation-bound. The framework we propose - 'computational identifiability' - is to instead define a finite computational search procedure for an empirical estimator. If this process finds an estimator empirically, within a desired error tolerance, then identifiability is satisfied, conditional on the specified assumptions of the search (i.e., a prior distribution over the parameters) and conditional on the search procedure itself. Through several experiments, we demonstrate how this framework allows us to answer fine-grained, practical identification questions, such as identification with small finite samples, with ambiguous graphical criteria, with mixed observational-interventional data, and across counterfactual data and estimands. Code is available at https://github.com/lbynum/metadentify.

03.
arXiv (CS.AI) 2026-06-19

Systematic Study of Dysarthric Speech Recognition: Spectral Features and Acoustic Models

arXiv:2606.19793v1 Announce Type: cross Abstract: The challenge associated with recognizing dysarthric speech primarily arises from pronounced acoustic variability attributed to impaired articulatory precision. Past research has demonstrated improved recognition through the use of hybrid DNN/HMM sequence discriminative training. This paper presents a comprehensive investigation of various combinations of acoustic features tailored to different Acoustic Models, offering suitable feature selections for each. The incorporation of Pitch features notably improved recognition performance, especially for sentence recognition tasks involving dysarthric speech. Through a systematic examination of the TORGO database, we have demonstrated the potential to enhance the performance of the state-of-the-art Factorized Time Delay Neural Network (F-TDNN) model for recognizing dysarthric speech. Our methods, implemented with the F-TDNN model, resulted in a 4.65\% relative improvement in isolated word recognition and a 4.63\% relative improvement in sentence recognition for dysarthric speech, compared to previous research. This improvement effectively compensates for speech variability, attributable to our deliberate selection of the number of overlapping frames between consecutive training example chunks.

04.
arXiv (CS.CV) 2026-06-18

Seeing Before Reasoning: Decoupling Perception and Reasoning for Shortcut-Resilient Multimodal On-Policy Self-Distillation

On-policy self-distillation (OPSD) trains a model on its own rollouts and uses a frozen copy to provide dense token-level targets conditioned on a reference target. This works well for LLM reasoning, but a direct extension to multimodal large language models (MLLMs) can create a shortcut: the privileged target may guide tokens mainly based on the text reference target rather than the image. We propose ViGOS, a visually grounded OPSD framework for MLLM post-training. The student first writes a visual description and then reasons toward the final answer. For valid rollouts, an image-only perception teacher supervises the description, while a privileged reasoning teacher supervises the reasoning and final answer on the same student prefix. A reference teacher is used only for invalid rollouts to recover the output format. Across general vision-language, expert reasoning, visual math, spatial grounding, and visual-language-prior benchmarks, ViGOS keeps the main benefits of OPSD and improves image-grounded behavior in shortcut-prone settings.

05.
bioRxiv (Bioinfo) 2026-06-23

CellOS: Learning a World Model of Cellular State through Joint Embedding Prediction

Foundation models learned from single-cell transcriptomes are central to the prospect of AI virtual cell that can represent, query and predict cellular state. However, most current single-cell foundation models learn from a single view of gene expression and are optimized primarily through reconstruction or next-token prediction. As a result, they capture expression abundance but can-not explicitly reconcile complementary views of cellular state. Here we present CellOS, a multi-view foundation model that learns cellular representations from paired expression and perception views. CellOS integrates complementary views through a scalable three-stage training strategy that combines causal cell-sentence language modelling, function-preserving dense-to-mixture-of-experts expansion and latent-space alignment via an LLM-JEPA objective. Using this framework, we trained a 12-billion-parameter model on 390.5 million single-cell transcriptomes. Across diverse benchmarks spanning cell-state annotation, batch integration and perturbation-response prediction, CellOS consistently outperformed state-of-the-art single-cell foundation models in cell-state annotation and perturbation-response prediction while preserving robust batch integration. Together, these results suggest that predictive alignment between complementary cellular views provides a scalable path toward representation-centric cellular world models and transferable AI virtual cells.

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

Attacking the First-Principle: A Black-Box, Query-Free Targeted Mimicry Attack on Binary Function Classifiers

arXiv:2605.18231v2 Announce Type: replace Abstract: Binary function classifiers play a crucial role in maintaining the security and integrity of software systems by detecting malicious code and unauthorized modifications. However, machine learning-based classifiers are vulnerable to adversarial attacks that can evade detection. In this study, we present Kelpie, a novel framework for executing mimicry attacks, a stronger type of targeted evasion attacks, on binary function classifiers in a black-box, zero-query setting. Unlike previous approaches that rely on querying the target classifier to refine untargeted evasion attacks, Kelpie leverages code transformations that preserve the functionality of malicious payloads while causing them to be misclassified as we want. Through extensive experimentation, we demonstrate that Kelpie can successfully execute mimicry attacks against six state-of-the-art binary function classifiers representing different model architectures without requiring direct interaction with them. We further validate our approach with a practical demonstration, involving a keylogger and a wiper concealed within benign-looking functions embedded in an application. This work, to our best knowledge, is the first to demonstrate such a mimicry attack in a black-box, zero-query context, raising important questions about the reliability and security of existing machine learning-based binary function classifiers.

07.
arXiv (CS.AI) 2026-06-16

Multi-Grade Deep Learning for Partial Differential Equations with Applications to the Burgers Equation

arXiv:2309.07401v2 Announce Type: replace-cross Abstract: Deep neural networks (DNNs) show great promise for solving partial differential equations (PDEs), but their deep architectures introduce complex, large-scale, non-convex optimization challenges. Nonlinear PDEs, like the viscous Burgers' equation, compound these difficulties due to steep gradients and shock-like solutions. To address this, we propose a two-stage multi-grade deep learning (TS-MGDL) method. In the first stage, shallow networks are trained progressively grade by grade to fit the target function from low- to high-frequency components; previously learned grades are frozen, and each new residual block is trained solely to minimize the remaining approximation error. The second stage unfreezes and retrains selected layers using the first-stage network as initialization, achieving an interpretable, stable hierarchical refinement while mitigating optimization complexity. Furthermore, we theoretically prove that each grade and stage in TS-MGDL monotonically reduces the loss function under an appropriate optimization strategy. Numerical experiments on 1D, 2D, and 3D viscous Burgers' equations demonstrate that TS-MGDL significantly outperforms single-grade learning (SGL), reducing predictive errors by up to a factor of 60.

08.
arXiv (CS.CL) 2026-06-12

Recursive Agent Harnesses

Recursive language models (RLMs) showed that recursion over model calls is an effective strategy for long-context reasoning, and production coding agents have begun to write code that spawns subagents at scale, most recently in Anthropic's dynamic workflows. We name and study the pattern between these two lines of work, where the recursive unit is a full agent harness with filesystem tools, code execution, and planning rather than a model call with no tools. We call this the Recursive Agent Harness (RAH) and frame it as harness recursion, the code-first extension to the model recursion of RLMs. A parent agent generates and runs an executable script that spawns subagent harnesses in parallel for fine-grained workloads and uses structured function calls for small subtasks. We provide a controlled evaluation on long-context reasoning. With the backbone held fixed at GPT-5 to match the published Codex and RLM baselines, RAH improves the Codex coding-agent baseline from 71.75% to 81.36% on Oolong-Synthetic (199 samples, 13 context-length buckets up to 4M tokens), a gain attributable to the harness rather than the model. With a stronger backbone, Claude Sonnet 4.5, the same design reaches 89.77%.

09.
arXiv (CS.AI) 2026-06-16

MASCOT-Android: A Curated Dataset and Automated Collection Pipeline for Android Malware Source Code Specimens

arXiv:2606.16072v1 Announce Type: cross Abstract: Compared with binaries and decompiled code, malware source code more directly reflects the attackers' original intent. However, the scarcity of source code and the high cost of manual review make such datasets difficult to build and maintain. We propose MASCOT-Android, a curated dataset of Android malware source code and an automated collection framework for scalable malware source code discovery on GitHub. A key finding of our work is that repository-level documentation alone provides a strong signal for malware source code collection. Our model extracts character-level TF-IDF features from 8,772 malware and 25,747 benign README documents and trains a LinearSVC classifier to distinguish malware repositories. This README-only model achieves an accuracy of 96.28\% and an FPR of 1.06\% in local evaluation. In addition, the model outputs confidence scores, allowing users to adjust the decision threshold to balance FPR and coverage, which is practical in real-world malware source code collection.

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

Large-Scale OD Matrix Estimation with A Deep Learning Method

arXiv:2310.05753v2 Announce Type: replace Abstract: The estimation of origin-destination (OD) matrices is a crucial aspect of Intelligent Transport Systems (ITS). It involves adjusting an initial OD matrix by regressing the current observations like traffic counts of road sections (e.g., using least squares). However, the OD estimation problem lacks sufficient constraints and is mathematically underdetermined. To alleviate this problem, some researchers incorporate a prior OD matrix as a target in the regression to provide more structural constraints. However, this approach is highly dependent on the existing prior matrix, which may be outdated. Others add structural constraints through sensor data, such as vehicle trajectory and speed, which can reflect more current structural constraints in real-time. Our proposed method integrates deep learning and numerical optimization algorithms to infer matrix structure and guide numerical optimization. This approach combines the advantages of both deep learning and numerical optimization algorithms. The neural network(NN) learns to infer structural constraints from probe traffic flows, eliminating dependence on prior information and providing real-time performance. Additionally, due to the generalization capability of NN, this method is economical in engineering. We conducted tests to demonstrate the good generalization performance of our method on a large-scale synthetic dataset. Subsequently, we verified the stability of our method on real traffic data. Our experiments provided confirmation of the benefits of combining NN and numerical optimization.

11.
arXiv (CS.CV) 2026-06-12

Towards Effective Waste Segmentation for Automated Waste Recycling in Cluttered Background

Rapid expansion of urban areas and population growth is causing an immense increase in waste production, which demands the need for efficient and automated waste management. In this scenario, automated waste recycling (AWR) using deep learning methods can assist humans in optimal waste management. Recent deep learning approaches for AWR provide promising waste segmentation performance, however, these methods rely on large backbone networks that are inefficient for AWR systems and suffer from performance deterioration in cluttered scenes. To this end, an optimal waste segmentation network is introduced which effectively utilizes the spatial domain to capture localized structural dependencies and the spectral domain to efficiently extract global contextual relationships. This cascaded design allows the network to progressively leverage both local and global representations across complementary domains to highlight the semantic information necessary for effective segmentation of various waste objects. Furthermore, auxiliary feature enhancement module (AFEM) is introduced to enhance the target objects' boundaries and blob amplification for better segmentation in cluttered scenarios. Extensive experimentation on ZeroWaste-aug, ZeroWaste-f and SpectralWaste datasets reveals the merits of the proposed method.

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

Continuum Neural Momentum Eigenstate for Variationally Solving Quasiparticles

arXiv:2606.12928v1 Announce Type: cross Abstract: We design the first neural quantum state for continuum particles that, for any chosen allowed momentum $\mathbf{k}$, is by construction an exact eigenstate of total momentum with eigenvalue $\mathbf{k}$. Our architecture, EVE, enables off-the-shelf VMC to solve for momentum-sector ground states. We test EVE on 2D bosons with mutual $1/r$ interactions, finding that a single unified ansatz is capable of describing four qualitatively different states: superfluid, roton, crystal, and phonon. At different densities, we extract the underlying phase of matter from the dispersion's shape. At $r_s = 20.0$, we see the roton minimum at finite $k$ expected of a superfluid. At $r_s = 100.0$, we see striking zone folding indicative of crystalline order, with periodically spaced minima representing floating crystals connected by phonon arcs in between. Using density-density correlation functions, we confirm the phase diagnoses and probe the excitations' correlation structures. Finally, we analyze the roton's phase texture and find unexpected multi-particle phase strings, formed when several vortex dipoles merge, leaving two vortices connected by a phase slip.

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

VoidPadding: Let [VOID] Handle Padding in Masked Diffusion Language Models so that [EOS] Can Focus on Semantic Termination

MDLMs generate text by denoising a preallocated masked response canvas, making response-length modeling central to instruction tuning. Existing MDLMs often inherit the autoregressive convention of using repeated \texttt{[EOS]} tokens for padding during instruction tuning, giving \texttt{[EOS]} a dual role as both a semantic terminator and a padding token. We show that this dual role is a root cause of \texttt{[EOS]} overflow under large-block decoding. To decouple these roles, we propose VoidPadding, which introduces \texttt{[VOID]} for padding and reserves \texttt{[EOS]} for termination. During inference, the learned \texttt{[EOS]} signal enables early stopping, while the learned \texttt{[VOID]} signal guides adaptive response canvas expansion. On Dream-7B-Instruct, VoidPadding improves the block-size-averaged four-task mean across mathematical reasoning and code generation benchmarks by \(+17.84\) points over the original model and \(+6.95\) points over RainbowPadding, while reducing decoding NFE by 55.7\% on average. Code is available at https://github.com/Haru-LCY/VoidPadding.

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

Running hardware-aware neural architecture search on embedded devices under 512MB of RAM

arXiv:2606.14824v1 Announce Type: cross Abstract: This document proposes a novel approach to hardware-aware neural architecture search (HW NAS) that considers the resources available on the computing platform running it, enabling its execution on various embedded devices. The presented HW NAS produces tiny convolutional neural networks (CNNs) targeting low-end microcontroller units (MCUs), typically involved in the Internet of Things (IoT) or wearable robotics, opening new use cases. A gateway could run it to tailor CNNs' architecture on the acquired data without using external servers, ensuring privacy. The proposed technique achieves state-of-the-art results in the human-recognition tasks on the Visual Wake Word dataset, a standard TinyML benchmark, on several embedded devices.

16.
arXiv (math.PR) 2026-06-11

Consensus on Dynamic Stochastic Block Models: Fast Convergence and Phase Transitions

arXiv:2209.03999v2 Announce Type: replace Abstract: We introduce two models of consensus following a majority rule on time-evolving stochastic block models (SBM), in which the network evolution is Markovian or non-Markovian. Under the majority rule, in each round, each agent simultaneously updates their opinion according to the majority of their neighbors. Our network has a community structure and randomly evolves with time. In contrast to the classic setting, the dynamics is not purely deterministic, and reflects the structure of SBM by resampling the connections at each step, making agents with the same opinion more likely to connect than those with different opinions. In the Markovian model, connections between agents are resampled at each step according to the SBM law and each agent updates their opinion via the majority rule. We prove a power-of-one type result, i.e., any initial bias leads to a non-trivial advantage of winning in the end, uniformly in the size of the network. In the non-Markovian model, a connection between two agents is resampled according to the SBM law only when at least one of them changes opinion and is otherwise kept the same. We identify the phase-transition threshold, up to the second-order leading term, between halting and fast convergence to consensus. We also give sufficient initial-lead conditions for consensus to occur within one, two, or three rounds.

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

Spatio-Temporal Fusion Model for Standard View Classification of Echocardiographic Videos

Automated classification of standard echocardiographic views is crucial for efficient clinical workflow but faces three main challenges. First, publicly available datasets are scarce and limited in scale and view coverage. Second, the performance of some modern video-level architectures for echocardiographic view classification remains underexplored. Third, some view categories exhibit highly similar spatial appearances, making single-frame features insufficient for discrimination, while heterogeneous frame quality complicates robust temporal information fusion. To address these challenges, we release the Echocardiographic Videos of Nine Views (EV9V) dataset, comprising 5,138 videos, 910,579 frames, and 9 standard views, which is, to the best of our knowledge, the largest publicly available echocardiography video dataset. Using EV9V, we systematically benchmark representative video classification architectures, including Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs), and Transformers. Furthermore, we propose a Spatio-Temporal Fusion Model (STFM), an efficient dual-stream CNN-LSTM (Long Short-Term Memory) framework that jointly captures spatial anatomical structures and temporal cardiac dynamics. The proposed framework leverages uncertainty-aware learning to preferentially sample representative video segments during training and evidence-based fusion during inference, improving robustness to variations in frame quality across echocardiographic videos. Extensive experiments demonstrate that our method achieves competitive performance across diverse video classification models, validating the effectiveness of uncertainty-aware spatio-temporal learning for echocardiographic view classification. The code is available at https://github.com/bgx666/stfm.

18.
arXiv (CS.LG) 2026-06-12

PhysMetrics.Weather: An Evaluation Framework for Physical Consistency in ML Weather Models

arXiv:2606.10642v2 Announce Type: replace Abstract: Machine learning weather prediction (MLWP) models have achieved impressive forecasting performance at a small fraction of the computational costs required for traditional physics-based methods. However, they are primarily (1) data-driven and (2) evaluated using pixel-wide error metrics (e.g., RMSE), so there are no guarantees that their forecasts are consistent with known physical laws. We introduce PhysMetrics$.$Weather, an evaluation framework that assesses the physical realism of MLWP models across three types of metrics: conservation, spectral, and dynamical. By quantifying physical realism, this tool guides the development of physics-informed architectures and helps evaluate whether MLWP models are reliable for operational use. Our framework is available on Github at https://github.com/Emmakast/PhysMetrics.Weather.

19.
arXiv (quant-ph) 2026-06-17

Fabless Quantum Chip Design and Commercial Production

arXiv:2606.17956v1 Announce Type: new Abstract: This paper proposes a fabless quantum-chip design and production architecture for superconducting quantum computing, centered on the SPICE-Q multiphysics simulation framework. The proposed ecosystem connects process-certified quantum PDKs, parameterized device cells, traceable model cards, SPICE-Q physical modeling languages, unified Q-EDA flows, foundry sign-off rules, cryogenic test feedback, and reusable quantum IP. In this model, design firms do not merely outsource fabrication; they prepare verified tape-outs under standardized process constraints and calibrated physical models. Its economic value lies in reducing repetitive device debugging, process exploration, and low-level layout effort, while its feasibility depends on PDK maturity, foundry yield, cryogenic test throughput, model-prediction accuracy, data-feedback mechanisms, and IP licensing boundaries. We argue that superconducting quantum chips can move from the current largely vertically integrated development model toward a fabless-foundry ecosystem only when hardware design is supported by standardized, verifiable, and reusable software and process interfaces. The required pillars are certified PDKs, PCell-based parameterized design, SPICE-Q cross-physics simulation, end-to-end Q-EDA automation, and a tradable quantum-IP market. By adapting lessons from the classical semiconductor industry to quantum hardware, this framework defines a path toward scalable, manufacturable, and commercially reusable superconducting quantum-chip design.

20.
Nature (Science) 2026-06-16

Daily briefing: How many elementary particles are there?

Authors:

Estimates range from 17 to 995.5. Plus, one man with paralysis is using a brain–computer interface at home and GLP-1 obesity drugs appear to boost testosterone and sperm quality. Estimates range from 17 to 995.5. Plus, one man with paralysis is using a brain–computer interface at home and GLP-1 obesity drugs appear to boost testosterone and sperm quality.

21.
arXiv (quant-ph) 2026-06-15

Efficient and simple Gibbs state preparation of the 2D toric code via duality to classical Ising chains

arXiv:2508.00126v2 Announce Type: replace Abstract: We introduce the notion of polynomial-depth duality transformations, which relates two sets of operator algebras through a conjugation by a poly-depth quantum circuit, and make use of this to construct efficient Gibbs samplers for a variety of interesting quantum Hamiltonians as they are poly-depth dual to classical Hamiltonians. This is for example the case for the 2D toric code, which is demonstrated to be poly-depth dual to two decoupled classical Ising spin chains for any system size, and we give evidence that such dualities hold for a wide class of stabilizer Hamiltonians. Additionally, we extend the above notion of duality to Lindbladians in order to show that mixing times and other quantities such as the spectral gap or the modified logarithmic Sobolev inequality are preserved under duality.

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

Proact-VL: A Proactive VideoLLM for Real-Time AI Companions

Proactive and real-time interactive experiences are essential for human-like AI companions, yet face three key challenges: (1) achieving low-latency inference under continuous streaming inputs, (2) autonomously deciding when to respond, and (3) controlling both quality and quantity of generated content to meet real-time constraints. In this work, we instantiate AI companions through two gaming scenarios, commentator and guide, selected for their suitability for automatic evaluation. We introduce the Live Gaming Benchmark, a large-scale dataset with three representative scenarios: solo commentary, co-commentary, and user guidance, and present Proact-VL, a general framework that shapes multimodal language models into proactive, real-time interactive agents capable of human-like environment perception and interaction. Extensive experiments show Proact-VL achieves superior response latency and quality while maintaining strong video understanding capabilities, demonstrating its practicality for real-time interactive applications.

23.
bioRxiv (Bioinfo) 2026-06-17

MetaHarmonizer: robust biomedical metadata harmonization and a contamination control for inflated LLM performance on public benchmarks

Public biomedical repositories hold substantial reuse potential, but inconsistent metadata routinely blocks integration across studies. Recent LLM-based harmonization approaches address scale but suffer from non-determinism, hallucinated ontology terms, and, in their highest-accuracy configurations, dependence on proprietary APIs or labeled fine-tuning data. A more fundamental concern is that LLM accuracies on widely-used public benchmarks may substantially inflate transferable capability: under a contamination-controlled evaluation protocol we developed, the apparent LLM-only advantage on the GDC schema-mapping benchmark is inverted, and three out of five LLMs recover 80 -100% of GDC identifiers from zero-schema context, suggesting direct memorization. Building on this insight, we present MetaHarmonizer, an automated metadata harmonization system designed to be robust by construction: SchemaMapper aligns attribute names across schemas, and OntologyMapper standardizes values to controlled vocabularies. Both modules implement a multi-stage cascade that escalates to more resource-intensive methods only when earlier stages fall short, with all candidates grounded in pre-defined controlled vocabularies to preclude hallucinated outputs and LLMs used only as bounded preprocessing components rather than inference-time dependencies. On the GDC schema-matching benchmark, SchemaMapper with the deployment-optimized LLM-generated alias dictionary achieved 71.6% Top-1 accuracy and the higher Recall@GT than Magneto bipartite variants, recovering significantly more ground-truth mappings; with the best performing alias dictionary, it reached the highest Top-1/Top-5/Recall@GT, and also matched the best Magneto reranker (fine-tuned LLM-reranker) on MRR; and it also outperforms LLM-only performance under contamination-controlled conditions. On four EFO benchmarks, OntologyMapper achieved 77.9 - 95.5% Top-1 accuracy, outperforming text2term by up to 16.4 pp and direct LLM inference (against the smaller corpus) by 19.2 pp because memorization is not a viable shortcut for this task. Across both modules, calibrated confidence scores separate correct from incorrect predictions (AUC 0.73 - 0.94), enabling principled human-in-the-loop triage. Inference is fully local, deterministic, and computationally efficient - seconds on schema mapping and under a minute for ontology mapping of up to ~7,000 terms against the pre-indexed 33,230-term corpus. Released as a Python package with a domain-agnostic architecture, MetaHarmonizer provides a scalable foundation for improving the FAIRness of biomedical data and enabling cross-study integration, alongside an evaluation methodology applicable to any LLM-augmented bioinformatics benchmark built on public benchmarks.

24.
medRxiv (Medicine) 2026-06-22

Development of a Novel Risk Prediction Model for Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD): A Longitudinal Study

Background: Interstitial lung disease (ILD) is one of the most common and potentially most devastating extra-articular complication of rheumatoid arthritis (RA) and is associated with substantial morbidity and mortality. However, reliable tools for the early identification of ILD in patients with RA remain limited. This study aimed to identify plasma protein biomarkers of RA-ILD and develop an interpretable machine learning model for risk prediction using data from the UK Biobank. Methods: We first evaluated the association between baseline RA and the risk of incident ILD in the UK Biobank using Cox proportional hazards models. Mendelian randomization analysis was then performed to investigate the potential causal relationship between RA and ILD. Finally, we analyzed 2,920 plasma proteins measured using the Olink platform in 781 eligible RA patients. Proteins associated with ILD risk were identified using Cox proportional hazards models and subsequently used to construct eight machine learning models. Model performance was assessed using the receiver operating characteristic curve (ROC) and decision curve analysis. The best-performing model was further interpreted using Shapley additive explanations (SHAP) to evaluate feature importance. Results: Compared with participants without RA, Patients with baseline RA had a significantly higher risk of developing ILD (Hazard ratio: 4.425, 95% CI: 3.549,5.518). The MR supported a potential causal association between RA and ILD (Odds ratio: 1.227, 95% CI: 1.121,1.343). Among the eight machine learning models, the CatBoost model showed the best performance, achieving an area under the curve (AUC) of 0.884 (95% CI: 0.773,0.996). The SHAP analysis identified LAG3, NPC2, and LAMP3 are the three most important plasma protein predictors of ILD development in patients with RA. Conclusion: Plasma proteomics combined with machine learning may provide a promising approach for identifying biomarkers and predicting ILD risk in patients with RA. LAG3, NPC2, and LAMP3 may serve as candidate biomarkers for RA-ILD and warrant further validation. Keywords: Rheumatoid arthritis, Interstitial lung disease, Mendelian randomization, Machine learning, Plasma proteins.

25.
medRxiv (Medicine) 2026-06-22

Integration of lung tissue proteomics and genome-wide association data to identify lung cancer susceptibility proteins and potential drug targets

Background: Proteins directly impact disease development and act as drug targets. Therefore, we integrated genomic and lung tissue proteomics data to identify lung cancer susceptibility proteins, elucidating genetic mechanisms and candidate drug targets. Method: We profiled the proteome and genome in non-neoplastic lung tissue from 200 lung cancer patients. Using this data, we constructed genetic models to predict abundance across the proteome in lung tissue. We applied these models to genome-wide association study (GWAS) data from 55,174 lung cancer cases and 1,294,174 controls to evaluate their associations with the risk of lung cancer, overall and by major histological subtypes. Bayesian colocalization and Mendelian randomization (MR) analyses were used to prioritize putative causal proteins, which were cross-referenced with three main drug-protein databases to identify potential therapeutic targets. Results: We identified 29 proteins associated with lung cancer risk at a false discovery rate < 5%, including 25 for overall lung cancer, two (AQP3 and IL18) specifically for adenocarcinoma, and another two (HMGN2 and HLA-DMB) for squamous cell carcinoma. Of them, genes encoding 17 proteins reside at least 2Mb away from any known GWAS risk loci, including 14 for overall lung cancer (HYI, GPX1, GMPPB, DSP, HDDC2, MTCH2, SUOX, JMJD7, PDIA3, IL16, IQGAP1, SULT1A2, ARHGAP27, and TYMP) and three for subtypes (AQP3, IL18, and HMGN2). Among the 12 proteins located within the known risk loci, EPHX2, CLDN18, PSMD5, and CYP2S1 proteins showed an association independent of the proximal GWAS-identified lead variant. Colocalization and/or MR analysis suggested 11 potential causal proteins. Five of these candidate causal proteins (DSP, CLDN18, IQGAP1, IL18 and TYMP) are targeted by nine drugs already approved by the FDA or in phase III trials. Conclusion: Our study identified novel lung cancer susceptibility proteins and potential drug targets, offering valuable insights into lung cancer biology and future translational utilities.