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

BALTO: Balanced Token-Level Policy Optimization for Hallucination Mitigation

Hallucinations remain a major obstacle to deploying large language models (LLMs) in knowledge-intensive settings, where generated responses must be faithfully grounded in provided evidence. Reinforcement learning (RL) is a promising direction for hallucination mitigation, but response-level faithfulness rewards suffer from a granularity mismatch: localized hallucinations can cause supported content to receive spurious penalties. Although recent work introduces fine-grained feedback such as claim-level verification and token-level rewards, unbalanced credit assignment can still induce length, verbosity, or optimization-noise biases. We propose BALTO, a Balanced Token-level Policy Optimization framework for hallucination mitigation. BALTO extracts checkable factual claims, verifies them against the reference context, and projects claim-level judgments to token-level labels. A balanced token-level credit assignment mechanism is introduced into the framework. This design redistributes probability mass from unsupported content toward faithful content, rather than suppressing the entire response. We systematically analyze the limitations of response-level rewards from a theoretical standpoint, and prove BALTO's advantages in training stability and optimization efficiency for hallucination mitigation. Experiments on ConFiQA, RAGTruth, and FinLLM-Eval show that BALTO achieves the highest faithfulness across all six model–benchmark settings and consistently outperforms existing post-training baselines in Q-Score, demonstrating a stronger faithfulness–informativeness trade-off.

02.
arXiv (quant-ph) 2026-06-15

Gaussian mode coupling of spectrally broadband photons from bulk spontaneous parametric down-conversion: A spatial-spectral mode analysis of fiber coupling

arXiv:2602.23238v2 Announce Type: replace Abstract: Photon sources based on spontaneous parametric down-conversion (SPDC) are central to experimental quantum optics and quantum technologies. Their performance is commonly quantified by three metrics: pair-collection probability, heralding efficiency, and spectral purity. In bulk-crystal SPDC, these metrics are known to be mutually constrained, yet the physical origin of the resulting trade-offs is often obscured. We show that these trade-offs originate from the frequency-dependent population of discrete spatial modes in the SPDC emission. By performing a Laguerre-Gauss mode decomposition at each frequency component, we show how spectral-spatial non-separability impacts collection probability, heralding efficiency, and purity. We apply this framework to two widely used quasi-phase-matching configurations: collinear degenerate type-0 and type-II SPDC in periodically poled bulk crystals, and quantify how different phase-matching functions shape the spectral-spatial mode structure. In particular, for type-II SPDC we compare standard periodically poled and aperiodically poled Gaussian phase matching. We experimentally validate some of our theoretical results using spatial- and spectral-projection measurements. This spectral-spatial mode analysis provides a quantitative and predictive framework for understanding and engineering bulk-crystal photon sources, enabling systematic multi-parameter optimization beyond qualitative design guidelines.

03.
arXiv (CS.CL) 2026-06-16

SimSiam Naming Game: A Unified Approach for Emergent Communication and Representation Learning

Emergent Communication (EmCom) investigates how agents develop symbolic communication through interaction without predefined language. Recent frameworks, such as the Metropolis–Hastings Naming Game (MHNG), formulate EmCom as the learning of shared external representations negotiated through interaction under joint attention, without explicit success or reward feedback. However, MHNG relies on sampling-based updates that suffer from high rejection rates in high-dimensional perceptual spaces, making the learning process sample-inefficient for complex visual datasets. In this work, we propose the SimSiam Naming Game (SSNG), a feedback-free EmCom framework that replaces sampling-based updates with a symmetric, self-supervised representation alignment objective between autonomous agents. Building on a variational inference–based probabilistic interpretation of self-supervised learning, SSNG formulates symbol emergence as an alignment process between agents' latent representations mediated by message exchange. To enable end-to-end gradient-based optimization, discrete symbolic messages are learned via a Gumbel–Softmax relaxation, preserving the discrete nature of communication while maintaining differentiability. Experiments on CIFAR-10 and ImageNet-100 show that the emergent messages learned by SSNG achieve substantially higher linear-probe classification accuracy than those produced by referential games, reconstruction games, and MHNG. These results indicate that self-supervised representation alignment provides an effective mechanism for feedback-free EmCom in multi-agent systems.

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

Algebraic Dead Directions in LayerNorm Transformers: A Forward-Pass-Only Diagnostic at LLM Scale

arXiv:2606.19491v1 Announce Type: new Abstract: Pretrained transformers sit near singular minima of the loss, where the Fisher information metric degenerates along dead directions: directions in parameter space along which the directional Fisher vanishes. Locating such a direction normally needs a forward pass and an eigendecomposition of activations, or a sampling-based complexity estimate; none returns a direction computable from the network's parameters alone. We give one, for LayerNorm transformers. The inverse-scale direction $\gamma^{-1}/\|\gamma^{-1}\|$ of the LayerNorm affine is an exact algebraic kernel of the post-final-norm centred activation covariance, for any input distribution, and induces a corresponding dead direction in parameter space. It is read from the LN scale parameter alone, with no forward or backward pass and no eigensolve: the cheapest dead-direction read, specific to LayerNorm. We test it on $14$ pretrained transformers ($9$ LayerNorm, $5$ RMSNorm; $160$M-$35$B; language and vision objectives). At random initialisation the predicted direction matches the measured bottom singular direction (one forward pass, direct SVD) to four decimal places on $9/9$ LayerNorm models, and is correctly absent on $5/5$ RMSNorm models, which lack the mean-subtraction projector that creates it. On the trained checkpoint the covariance eigenvalue along this direction deepens by ${\sim}10^3\times$ and further dead directions open; the random-init-to-trained gap is a one-forward-pass, per-checkpoint readout of singular structure along the predicted coordinate. Two consequences follow in closed form: the residual stream's smallest singular value is preserved block-to-block on $13/14$ transformers measured on their own input distribution, the one exception (Gemma$4$-$31$B) a genuine dead direction the same read pinpoints; and the kernel direction's presence classifies a transformer's normalisation from the parameters alone.

05.
arXiv (CS.LG) 2026-06-19

A fast direct solver based neural network for solving PDEs

arXiv:2606.19895v1 Announce Type: cross Abstract: The matrices arising from large scale $N$-body problems can be efficiently represented using hierarchical matrices, whose key idea is that the admissible off-diagonal sub-matrices can be well approximated by low-rank matrices across a hierarchy of matrix partitions. HODLR (Hierarchical Off-Diagonal Low-Rank) matrices are a subclass of hierarchical matrices in which all off-diagonal submatrices at every level of a recursive binary partition are low-rank. In this article, we present a neural network that learns the inverse operation of HODLR matrices based on the fast direct solver for HODLR matrices developed by Ambikasaran and Darve (2013). We further extend the architecture to learn nonlinear solution operators associated with PDEs by replacing some of the linear layers with deep sub-networks. We demonstrate the performance of the proposed architecture by performing a comprehensive set of experiments that include (i) solving a linear problem such as the Fredholm integral equation of the second kind, (ii) solving PDEs such as the nonlinear Schrödinger equation, Burgers' equation, and the steady-state Darcy's flow equation, (iii) generalization study across varying parameter values, (iv) comparing the inference time of the proposed network with the run time of a classical numerical solver, and (v) comparing the proposed network with some of the existing neural operator learning networks.

06.
arXiv (CS.AI) 2026-06-25

Stable-Shift: Biologically Structured Prediction of Transcriptional Responses to Unseen Gene Perturbations

arXiv:2606.24940v1 Announce Type: cross Abstract: Predicting transcriptional responses to genetic perturbations could reduce the experimental burden of functional genomics, but extrapolation to genes that were never perturbed during training remains difficult. We present Stable-Shift, a structured method for estimating unseen-gene responses. Stable-Shift aggregates single-cell measurements into perturbation-level expression shifts, fits a low-rank response basis using training perturbations only, and predicts an unseen gene's coordinates in that basis from biological context. The context combines STRING interactions, network structure, control-cell expression statistics, and Gene Ontology annotations; the evaluated implementation uses graph convolution to integrate these inputs. On the supplied K562 Perturb-seq benchmark, Stable-Shift obtained 0.592 cosine similarity, compared with 0.569 for GEARS, together with higher Spearman correlation and top-gene precision among the evaluated methods. Its mean cosine similarity over five unseen-gene splits was 0.589 +/- 0.008. The same ordering was observed in the supplied graph-aware, residualized, gene-space, and Norman-dataset comparisons. These results support further study of biologically structured latent-response prediction, while the lower gene-space accuracy and sensitivity to sparse graph neighborhoods limit the scope of the present conclusions.

07.
arXiv (CS.CL) 2026-06-25

Fault of Our Stars: Behavioral Drivers of Rating-Sentiment Incongruence

When people share experiences online, they often express thoughts in two ways: a star rating and a written review. In sentiment analysis, ratings are widely used as convenient weak labels for textual sentiment, yet whether the two actually agree is rarely questioned. This study investigates sentiment-rating incongruence, where the sentiment expressed in review text differs from the sentiment implied by the assigned star rating, in Sri Lankan tourism attraction reviews. A dataset of 16,156 reviews from 2010 to 2023 is analyzed using a transformer-based sentiment pipeline that derives textual sentiment independently of assigned ratings. Incongruence occurs in 18.6% of reviews and falls into six directional patterns, with Conservative Rater and Obligatory 5-Star behaviors accounting for the majority of mismatches. Prevalence also varies across venue types, with museums showing the highest rates. Statistical tests, logistic regression, Random Forest, and SHAP analysis identify venue type, reviewer expertise, review length, and temporal factors as contributors to rating-text divergence. Overall, this study demonstrates that star ratings are not interchangeable with textual sentiment and should be validated before being treated as ground-truth labels in NLP.

09.
arXiv (quant-ph) 2026-06-12

A Quantum Algorithm for Random Number Generation

arXiv:2606.13034v1 Announce Type: new Abstract: We present a quantum algorithm for random number generation that achieves a provable quadratic speedup over classical Markov chain mixing, building on the Diaconis-Shahshahani Fourier analysis of the top-to-random card shuffle. The algorithm integrates three quantum primitives into a unified mixing circuit: the Quantum Fourier Transform (QFT), which diagonalizes the Markov transition operator; controlled phase rotations, which encode the shuffle eigenvalue spectrum; and the Grover diffusion operator, which acts as a quantum analogue of the Aldous-Diaconis strong uniform stopping time by reflecting amplitudes about their mean at each iteration. For an n-qubit register, the mixing time is O(\sqrt{n \log n}) iterations. Extending to m qudits of local dimension d reduces this to O(\sqrt{\log_d N}) iterations, where N = d^m, compared to the classical O(n \log n) bound. The qudit formulation further reduces QFT circuit depth from O(\log^2 N) to O(\log_d^2 N) gates per layer by encoding the same N-state space using m = \log_d N subsystems instead of \log_2 N qubits. We validate both variants on IBM superconducting hardware.

10.
arXiv (CS.AI) 2026-06-12

Strategic Decision Support for AI Agents

arXiv:2606.12587v1 Announce Type: new Abstract: Traditionally, decision support studies how humans use machine learning models to make better decisions. In modern agentic systems, this division of roles is increasingly reversed: AI agents act on behalf of users, while humans and tools becomes support mechanisms around them. This role reversal brings reliability concerns to the forefront, since agentic errors can be consequential and agent behavior must remain aligned with human goals and constraints. Departing from the classical view of decision support, we revisit its two basic principles, the cost–value tradeoff of seeking support and the role of uncertainty quantification, in a setting where AI agents are the central actors. We propose a framework for strategic decision support for AI agents through an optimization problem that minimizes support usage subject to controlling a counterfactual missed-support error: the probability that the agent acts alone on instances where support would have materially improved its output. At the population level, we show that the optimal policy is a threshold rule on the value of support. Building on this structure, we develop an online algorithm that adaptively thresholds such a score and uses randomized exploration to control missed-support error without distributional assumptions. We further introduce a calibration-on-the-fly method that reduces unnecessary support calls online. We instantiate this framework across diverse scenarios, including information gathering, human–AI collaboration, and tool use, showing how each can be modeled through the same strategic decision-support lens. Experiments across these settings show that our method reliably controls the target error while substantially reducing support usage in practice.

12.
arXiv (math.PR) 2026-06-25

The relationship between the transition functions of the labeled and unlabeled versions of the infinitely-many-neutral-alleles diffusion model

Authors:

arXiv:2606.06739v2 Announce Type: replace Abstract: The transition function of the unlabeled infinitely-many-neutral-alleles diffusion model, as expressed by Zhou (2015), is derived from the transition function of the labeled infinitely-many-neutral-alleles diffusion model, slightly simplifying the derivation by Feng (2010).

13.
arXiv (CS.LG) 2026-06-24

KLip-PPO: A per-sample KL perspective on PPO-Clip

arXiv:2606.23932v1 Announce Type: new Abstract: Proximal Policy Optimization (PPO) is the standard policy-gradient algorithm for on-policy reinforcement learning. The literature presents it in two forms, a clipped surrogate that bounds the importance ratio between successive policies and a Kullback-Leibler penalty between them. These forms are treated as separate algorithms with their own gradients, their own hyperparameters, and their own reference implementations, and a sizeable body of empirical work compares them. We show that the gradient of the clipped surrogate is reproduced exactly by a Kullback-Leibler surrogate whose coefficient varies per sample, with closed-form dependence on the importance ratio and the advantage. The identity holds at every minibatch step and across the entire inner loop, and on five MuJoCo continuous-control benchmarks the two losses produce indistinguishable training curves. The reformulation exposes a structural feature of the clipped surrogate that the min notation hides. PPO-Clip's implicit per-sample penalty is a step function at the boundary of the trust region, and the shape of this coefficient is the natural design axis for generalising the algorithm. We sketch the resulting follow-up directions in the discussion.

14.
arXiv (CS.AI) 2026-06-19

ScholarQuest: A Taxonomy-Guided Benchmark for Agentic Academic Paper Search in Open Literature Environments

arXiv:2606.20235v1 Announce Type: cross Abstract: Academic paper search is a core step in scientific research, and LLM-based search agents are emerging as a promising paradigm for iterative, intent-driven literature exploration. However, existing benchmarks are insufficient for systematically evaluating agentic academic search under realistic open literature environments. We propose ScholarQuest, a large-scale, taxonomy-guided benchmark for agentic academic paper search. ScholarQuest is constructed from over 1,000 computer science topics and four representative research intents, including method-oriented, setting-anchored, comparison-based, and scope-controlled queries. It further provides scalable answer construction and a shared retrieval backend ScholarBase for reproducible evaluation. Benchmarking results show that agentic methods outperform single-shot retrieval baselines, yet the best-performing agent only achieves 0.314 Recall@100 and 0.355 Recall@All, indicating substantial room for improvement. In addition, analyses of search efficiency, intent-level robustness, and failure cases further highlight the benchmark's ability to provide multi-dimensional evaluation signals for academic paper search agents.

15.
arXiv (CS.AI) 2026-06-11

PermDoRA – Understanding Adapter Interference in Language Models: Limits of Parameter-Space Geometry

arXiv:2606.11262v1 Announce Type: cross Abstract: Access control in large language models (LLMs) requires modular mechanisms to enable domain-specific behavior without retraining or cross-domain interference. A common hypothesis is that interference during adapter composition arises from overlap in linear parameter updates, suggesting that enforcing orthogonality or directional independence should improve multi-domain performance. We test this hypothesis using DoRA-RBAC, a hierarchical adapter composition framework based on weight-decomposed low-rank adaptation. We compare conventional Euclidean merging with a geometry-aware Riemannian-inspired merging strategy that approximates the Frechet mean via normalized directional averaging across multiple QA benchmarks (GPQA, PubMedQA, SimpleQA, WMDP) on LLaMA-3.1-8B and Mistral-7B. Our results show that while single-domain performance matches LoRA, geometry-aware merging provides no consistent advantage over standard averaging in multi-domain settings.Diagnostic analysis further reveals that angular alignment and orthogonality of adapter updates are weak predictors of composition performance. These findings suggest that adapter interference is not governed primarily by parameter-space geometry, but is instead consistent with interactions in shared nonlinear representations.

16.
bioRxiv (Bioinfo) 2026-06-24

Beyond statistical significance: ranking transcription factor binding motifs by effect size

Chromatin immunoprecipitation-sequencing (ChIP-seq) has wide use in identifying transcription factor binding sites. DNA sequence motifs specific to a targeted transcription factor occur more frequently near ChIP-seq peak centres. The most common approach to quantifying relative motif enrichment ranks motifs by p-value . Because sample sizes can vary substantially across examined motifs, p-value magnitudes may reflect this heterogeneity rather than the biological effect of interest. As alternatives, we considered four ranking methods based on effect sizes: (a) a modified Cliffs delta, (b) the lower bound of a frequentist asymptotic confidence interval, (c) the lower bound of a frequentist finite-sample confidence interval, and (d) the lower bound of a Bayesian credible region. Through extensive simulations, the four alternatives better recovered the simulated central- enrichment ordering under heterogeneous sample sizes. Using published ChIP-seq data for GATA3, the effect size methods ranked the known targeted motif highest, even compared to highly similar motifs for other GATA family members, while p-value ranking did not. In a separate SRF application, all four alternative methods also consistently ranked the known motif highest. We recommend the asymptotic confidence interval lower bound for its simplicity, ease of implementation, and intuitive interpretation. The software is freely available (https://github.com/ScottMastro/motif-ranking).

18.
arXiv (CS.CL) 2026-06-17

A Red-Team Study of Anthropic Fable 5 & Opus 4.8 Models

Authors:

We evaluate the adversarial robustness of two frontier large language models (LLMs) developed by Anthropic, Fable 5 and Opus 4.8, against four families of automated jailbreak attack across 7 826 harmful intents spanning a ten-category harm taxonomy. Using the HackAgent red-teaming framework, hundreds of thousands of adversarial attempts were generated and every apparent success was independently re-adjudicated by a panel of three judge models (majority vote). Both models resist the majority of attacks, but the residual surface is larger than aggregate framing suggests: it is dominated by adaptive iterative attacks, while static obfuscation is near-fully neutralised. The strongest adaptive search (tree-of-attacks) breaks Opus 4.8 on 11.5% of intents overall, whereas Fable 5 stays in the single digits (6.1% worst-case). Aggregate rates therefore should not be read as reassurance. Even in these hardened configurations, the two models produced 1 620 (Opus 4.8) and 702 (Fable 5) panel-confirmed harmful completions spanning every harm category, located automatically, cheaply, and within the first one or two refinement steps by an attacker model with no human expert in the loop. The reasonable conclusion is that even the best, most-tested frontier models remain reliably breakable under sustained automated pressure.

19.
arXiv (CS.LG) 2026-06-15

Beyond the Training Distribution: Evaluating Predictions Under Distribution Shift and Selection Bias

arXiv:2606.14506v1 Announce Type: cross Abstract: Understanding how a prediction model will perform in a new environment before deployment is essential to preventing harm when algorithms inform decision-making. Two common sources of model performance degradation are (i) covariate shift, where the target covariate distribution differs from the source, and (ii) selective labels, where the observability of outcomes depends on historical decisions. We study pre-deployment model evaluation under the joint presence of covariate shift and labeling of outcomes selectively based on observed features. In particular, we present a double machine learning procedure for estimating the target risk of an arbitrary black-box prediction model under a general loss function. We show identification of this estimand under standard assumptions and derive a bias-corrected estimator based on the influence function of the target risk. Finally, we evaluate our estimator through experiments using the eICU electronic health records database, showing that it tracks the true target risk more accurately than methods that address either selective labels or covariate shift alone, as well as baselines that combine standard plug-in approaches.

20.
arXiv (CS.CL) 2026-06-17

Speaking in Self-Assessing Tongues: On the Verbalized Confidence of LLMs in Machine Translation

The rapid rise in popularity of large language models (LLMs) for translation calls for a thorough study of the reliability of their confidence in their own outputs. Unlike many generation tasks, translation errors and confidence levels can be useful at different levels of granularity (tokens, words, or spans). Unsupervised approaches based on internal signals like predicted probabilities can be misleading because they reflect certainty among alternatives rather than correctness. In addition, they require access to such internal signals. Here, we devise five verbalized methods of extracting an LLM's per-token confidence without those shortcomings and compare their reliability with that of the model's internal signals of certainty. We evaluate reliability using two forms of alignment: fine-grained error detection and calibration. For both, internal and verbalized methods perform similarly, although results vary by model. Interestingly, we find little to no correlation between internal and verbalized methods.

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

Heterogeneous SAR-optical fusion for near-real-time land use and land cover mapping under cloud contamination: A novel framework and global benchmark dataset

Optical remote sensing imagery is frequently degraded by cloud and cloud-shadow contamination, which limits its reliability for near-real-time land use and land cover (LULC) mapping. Although synthetic aperture radar (SAR) can provide cloud-penetrating structural information, existing SAR-optical fusion methods often assume reliable optical observations and insufficiently address the semantic uncertainty introduced by cloud contamination. To address this issue, we propose CloudLULC-Net, an end-to-end heterogeneous SAR-optical fusion framework that directly predicts LULC maps from cloud-contaminated Sentinel-2 imagery and temporally adjacent Sentinel-1 SAR observations. The proposed network incorporates optical reliability modulation to suppress unreliable optical responses, heterogeneous information adaptive aggregation to model high-order spatial-channel interactions between optical and SAR representations, and a unified semantic mapping transformer to organize fused features in a LULC-oriented latent space. A semantic anchor-guided optimization strategy is further introduced to improve the consistency of intermediate semantic representations. To support this task, we construct CloudLULC-Set, a large-scale benchmark dataset containing 40,223 curated SAR-optical-label triplets with pixel-level LULC annotations across diverse geographic regions and cloud conditions. Experimental results show that CloudLULC-Net achieves an OA of 86.60%, an F1-score of 83.29%, and an mIoU of 73.51%, outperforming representative heterogeneous reconstruction-first and end-to-end SAR-optical mapping methods. Comparisons with existing global LULC products and analyses under different cloud-cover levels further demonstrate the robustness and practical value of CloudLULC-Net for target-date LULC mapping in cloud-prone regions.The project is publicly available at: https://github.com/RSIIPAC/CloudLULC

22.
arXiv (CS.AI) 2026-06-24

Random coloured digraphs defined by a Markov logic network

arXiv:2606.23715v1 Announce Type: cross Abstract: A Markov Logic Network (MLN) is a probabilistic relational model used in Statistical Relational Artificial Intelligence for defining a probability distribution on the set of possible worlds with domain $D$ for an arbitrary finite domain $D$. An MLN consists of soft constraints with associated weights which are nonnegative real numbers. In this study we consider a language speaking about a property $P(x)$ and a relation $R(x, y)$. We consider an MLN for which every Boolean combination of $P(x)$ and $R(x, y)$ is a soft constraint (with associated weight). Let $n$ denote the size (cardinality) of the domain. We show that, for every choice of weights, if the weights are scaled by $1/n$ then, for every first-order sentence $\varphi$, the probability that $\varphi$ holds tends to either 0 or 1 as $n \to \infty$; that is, a 0-1 law for first-order logic holds. Morover, the limit probability does not depend on the weights. If we instead use the standard semantics of MLNs, in the case of which the weights are not scaled, then the limit behaviour is more complicated and depends on the weights. With unscaled weights we get 7 qualitatively different cases which depend on the weights. In some cases we have a 0-1 law for first-order logic, in some cases not, but we may still have a convergence law. The influence of the weights on the asymptotic probability of a first-order sentence may be in the form of a sudden ``phase transition'' from one of the 7 cases to another. The presence of a convergence law has positive implications for inference on large domains.

23.
arXiv (CS.CV) 2026-06-24

REDI-Match: Rotation-Equivariant Distillation for Efficient and Robust Dense Matching

Vision Foundation Models (VFMs) have significantly advanced dense feature matching, yet severe in-plane rotation remains a critical challenge. Existing solutions face a fundamental dilemma: data-driven methods require inefficient parameter scaling to implicitly learn rotations, whereas strictly equivariant networks lack the semantic capacity of modern VFMs. Consequently, current frameworks typically freeze VFMs and shift the entire burden of rotation generalization to the downstream decoder. To break this architectural bottleneck, we propose REDI-Match, an efficient framework driven by a novel Rotation-Equivariant Distillation (REDI) paradigm. Instead of relying on rotation data augmentation to establish rotational correspondences, REDI distills the non-equivariant semantic representations of a VFM into a lightweight, strictly rotation-equivariant encoder, leveraging an equivariant geometric architecture to constrain robust high-dimensional semantics. To fully exploit these features, we equip the decoder with an entropy-driven spatial alignment module. By evaluating discrete rotation hypotheses, this mechanism explicitly locks onto the canonical coordinate system, eliminating global ambiguity before continuous refinement. Extensive experiments demonstrate that REDI-Match establishes a new state-of-the-art (SOTA) across multiple benchmarks. Notably, it achieves a 13.89% absolute pose accuracy improvement on the highly challenging SatAst dataset while operating 1.9x faster than the current SOTA (RoMa v2), enabling real-time inference (~41 FPS) on a single RTX 4090 GPU. Code: https://github.com/YinjiGe/REDI-Match.

24.
bioRxiv (Bioinfo) 2026-06-16

Expanding gene regulatory networks from transcriptome data through graphical modeling with heterogeneous priors

Gene regulatory network inference is widely used to reconstruct large-scale networks and identify functional genes from transcriptome data. Meanwhile, in many biological fields, core regulatory genes have been extensively studied, leading to the establishment of small-scale gene regulatory networks, and novel genes connected to these networks remain to be identified. However, methods for expanding existing gene networks by identifying novel regulatory interactions, rather than reconstructing the entire network, are not well established. Here, we propose a method for gene network expansion that incorporates known regulatory relationships and evaluates each candidate gene individually to infer its regulatory connections to the existing network. Using simulated datasets from the DREAM4 benchmark and the PRECISE-1K experimental dataset, our method outperformed conventional methods by incorporating prior knowledge. In particular, it improved the ability to distinguish true regulatory interactions from indirect associations arising from strong correlations among genes in the existing network. The method also showed strong performance for interactions involving genes with high outdegree or centrality. Furthermore, it maintained stable performance as the size of the existing network increased and was robust to noise in prior information. These results demonstrate that our method provides an effective framework for expanding existing gene regulatory networks by leveraging prior knowledge.

25.
bioRxiv (Bioinfo) 2026-06-24

Pharmacological Stratification of Public Bioactivity Databases: A Reusable, OECD-Anchored Curation and Benchmarking Framework Demonstrated for Opioid Receptors

Public bioactivity databases are heterogeneous not only in measurement type, where binding affinities and functional potencies are reported on different scales, but in pharmacology: the same compound and target can carry agonist, antagonist, or inhibitor records measured through binding displacement, cAMP, {beta}-arrestin, or [35S]GTP{gamma}S readouts that quantify different biological events. Pooling these records produces models whose output is detached from any coherent pharmacological claim. Prior work has standardized bioactivity at scale and quantified the noise from mixing measurement types, but pharmacological mechanism and assay-readout class have not been treated as a primary axis of large-scale curation. This study presents an auditable, OECD-anchored framework that stratifies public records by action type and assay readout before modeling, converting heterogeneous data into externally validated, interpretable QSAR tasks that compose with existing standardization resources rather than replacing them. The framework is demonstrated on the four opioid receptors (MOR, DOR, KOR, and nociceptin/orphanin FQ, NOP). Four public sources were reconciled into 72,148 merged records and 50,977 curated measurements spanning 19,585 compounds, each carrying auditable attributes for source agreement, endpoint meaning, pharmacology class, assay readout, and trust tier. Receptor-level binding tasks formed a compact benchmark with strong locked external performance, including KOR pK (R2 = 0.79, n = 798) and DOR pK (R2 = 0.77, n = 736). Pharmacology- and readout-resolved functional endpoints yielded externally validated strata that pooled labels would obscure, including a MOR antagonist functional-inhibition endpoint (R2 = 0.86, n = 110) and agonist potency endpoints for DOR, KOR, and MOR (R2 up to 0.81). Comparison against a fully pooled baseline shows that pooled models either match stratified models on coherent endpoints or reach a deceptively high R2 on functional-IC endpoints by training predominantly on binding-displacement records, so the pooled number predicts affinity rather than functional activity. SHAP attribution indicates that binding and functional potency encode partially distinct structure-activity signals. The dataset contract, not model performance alone, defines the validity and scope of a QSAR claim, and stratification is a precondition for a functional model to support a defensible claim. Curation logic, derived tables, frozen data, and reproducibility artifacts are released.