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01.
arXiv (CS.CL) 2026-06-12

From Passive Generation to Investigation: A Proactive Scientific Peer Review Agent

Large language models (LLMs) have shown promise in automating scientific peer review. However, existing approaches often struggle to generate in-depth reviews supported by concrete evidence. We argue that a key limitation is the lack of flexibility to proactively investigate suspicious parts of a paper based on accumulated evidence, as human reviewers do. In this paper, we explore how to enable an LLM-based review agent to perform such proactive investigation. We find that this can be naturally formulated as a Markov Decision Process (MDP), and propose ProReviewer, a scientific peer review agent that proactively reviews a paper guided by a maintained, structured review log. The structured review log serves as a workspace for the agent to track evidence and intermediate findings collected during review. Experiments show that ProReviewer with an 8B backbone, trained by supervised fine-tuning and optimized by reinforcement learning, achieves the highest average score across five quality dimensions, outperforming prompt-based methods with much larger frontier LLMs by up to 39% and the strongest fine-tuned baseline by 16% relatively. It also attains the highest win rates against baselines in human evaluation.

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

PerceptionDLM: Parallel Region Perception with Multimodal Diffusion Language Models

Multimodal large language models (MLLMs) have achieved remarkable progress in visual understanding tasks. However, most existing MLLMs rely on autoregressive generation, which limits their efficiency for perception tasks that require captioning multiple regions. In this work, we propose PerceptionDLM, a multimodal diffusion language model optimized for efficient parallel region perception. Built upon PerceptionDLM-Base, a strong foundational baseline that achieves state-of-the-art performance among open-source diffusion MLLMs, our architecture fully leverages the parallel decoding nature of DLMs. Specifically, we introduce efficient prompting and structured attention masking to enable simultaneous perception of multiple masked regions, allowing the model to generate region descriptions in parallel at both the sequence and token levels. This design significantly improves inference efficiency compared with existing approaches that process regions sequentially. To systematically evaluate the parallelism property of visual perception capability for DLMs, we construct a new Parallel Detailed Localized Captioning Benchmark (ParaDLC-Bench) by scaling the DLC-Bench to include multiple region masks per image, enabling joint evaluation of both caption quality and inference efficiency. Experiments demonstrate that PerceptionDLM maintains competitive performance in region captioning while achieving substantial speed improvements for multi-region perception tasks. Our results highlight the potential of multimodal diffusion language models for efficient, parallel visual perception. To the best of our knowledge, we are the first to achieve parallel region caption and perception by leveraging the advantages of diffusion language models. Code, models, and datasets are released.

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

Prediction of Alzheimer's Disease Risk Factors from Retinal Images via Deep Learning: Development and Validation of Biologically Relevant Morphological Associations in the UK Biobank

The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using 62,876 CFPs from 44,501 unique participants from the UK Biobank, DL models were trained to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for continuous factors, outperforming most of the morphometry-machine learning models. Saliency-based score consistently highlighted biologically meaningful regions, particularly the optic nerve head and retinal vasculature. It also aligned with present morphometric variations. Several saliency-based scores differed significantly between incident AD and matched controls, suggesting potential overlap between retinal correlates of risk factors and preclinical AD-associated changes. CFP encodes retinal signatures linked to AD risk factors. Although not diagnostic, DL-derived retinal representations may uncover biologically meaningful risk-related structural changes mirroring the potential AD vulnerability.

04.
arXiv (CS.CL) 2026-06-15

Does the Judge Prefer English? Evaluating Language-Switching Invariance in LLM-as-a-Judge

Authors:

Large language models (LLMs) are now widely used as automatic judges for open-ended instruction-following evaluation. This practice is convenient, scalable, and often more semantically aware than reference-based metrics, but it also introduces a new reliability question: does a judge evaluate the quality of an answer, or does it also react to the language in which the comparison is presented? We propose Judge-LS, a lightweight meta-evaluation protocol that transforms LLMBar response-pair items into English, Chinese, and Chinese-English language-switched variants. A reliable judge should preserve its preference under label-preserving language transformations and should not prefer a language when two answers are translation-equivalent. We evaluate four API-accessible judges on the full 419-item LLMBar benchmark, producing 13,408 successful pairwise judgments. Across models, Chinese and language-switched presentations induce 10.7–14.4% preference flips relative to English, and all judges achieve their highest accuracy in English. However, translation-equivalent tie probes do not reveal a systematic English preference: most probes are judged as ties, and non-tie decisions more often favor Chinese. We add confidence intervals, paired significance tests, and an automatic transformation audit with a sensitivity analysis that excludes mechanically flagged high-risk variants. The experiment requires no model training, uses only API calls, and is feasible on modest local hardware.

05.
arXiv (CS.CV) 2026-06-12

Modality Forcing for Scalable Spatial Generation

Text-to-image (T2I) models contain rich spatial priors. Synthesizing photorealistic, cluttered scenes requires an understanding of geometry, including perspective and relative scale. Prior works adapt T2I models to leverage this prior for depth prediction, but they require dense depth data and involve complex recipes. We propose Modality Forcing, a simple, scalable post-training recipe for joint image-depth generation using a single DiT trained on sparse depth data. Modality Forcing enables conditional and joint generation of image and depth in any permutation by assigning separate noise levels per modality. Per-modality decoders let us train on sparse, real-world depth and achieve strong, generalizable depth prediction. We further show that Modality Forcing inherits the scalability of T2I pre-training: by training a set of T2I models from scratch (370M to 3.3B parameters), we find that larger models trained on more image data produce more accurate depth. Our strongest model is competitive with state-of-the-art monocular depth estimators and reduces AbsRel by 57% relative to existing joint image-depth generative models. These results provide strong evidence that image generation is a scalable pre-training objective for spatial perception. https://modality-forcing.github.io/

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

Phantoms and Disclosures: a Causal Framework for Auditing Synthetic Data

arXiv:2606.16952v1 Announce Type: cross Abstract: The rapid adoption of generative AI and Large Language Models (LLMs) has spurred interest in synthetic data as a privacy-preserving alternative to sensitive real-world datasets. However, generating high-utility synthetic data often carries the risk of memorizing and regurgitating private information from the training corpus. In this work, we present a customizable empirical auditing framework designed to detect and explain such data disclosures. Our framework introduces a mechanism to distinguish between "true disclosures"-where the system directly reproduces a user's information-and "phantom disclosures''-where the system incidentally generates a user's data. By partitioning input data into training and holdout sets and applying rigorous statistical hypothesis testing, we determine if observed disclosures are consistent with strict privacy baselines, such as zero-learning or specific Differential Privacy (DP) bounds. Crucially, this approach requires no model access, no canary insertion, and no reference model training -only the synthetic output and a held-out control set. We demonstrate that this framework effectively functions as a membership inference attack, providing empirical lower bounds on privacy leakage that are tighter than prior data-based auditing methods. Our approach is model-agnostic, applies to any synthetic data generation mechanism, and requires orders of magnitude fewer computational resources than shadow-model or canary-based alternatives.

07.
arXiv (CS.AI) 2026-06-19

Data Standards for Humanoid Robotics: The Missing Infrastructure for Physical AI

arXiv:2606.19769v1 Announce Type: cross Abstract: The scalability of humanoid robots will depend not only on models and hardware, but also on whether physical experience can accumulate across robots, tasks, organizations, and time. Drawing on the authors' work in developing ISO/WD 26264-1, Humanoid robot datasets – Part 1: General requirements, within ISO/TC 299/WG 16, this article argues that data standards are becoming foundational infrastructure for Physical AI. We develop three insights. First, humanoid robot data is embodied interaction data, not a collection of isolated digital samples; a useful dataset must preserve the relationship among robot body, action, task, scene, execution trace, and outcome. Second, its value depends on physical coherence: multimodal streams are reusable only when timing, coordinate frames, calibration, kinematics, units, and synchronization assumptions remain inspectable. Third, the main bottleneck is not only data scarcity, but non-cumulative data caused by high collection costs, data silos, and inconsistent evaluation. We argue that humanoid robot data standards address these bottlenecks by making embodied experience interpretable, shareable, traceable, and reusable. A general standard should provide horizontal infrastructure for lifecycle management, metadata, provenance, quality, versioning, and traceability, while capability-specific parts should define domain grammar for manipulation, locomotion, human-robot interaction, cognition, and future humanoid capabilities. As AI moves from screens into bodies, data standards must evolve from organizing digital information to structuring physical interaction.

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

ActionMap: Robot Policy Learning via Voxel Action Heatmap

Vision-language-action (VLA) models have advanced rapidly across backbones, training recipes, and data scale, yet the action decoder, which converts the backbone's hidden state into a continuous control signal, has barely changed and remains a single-point predictor across the majority of current VLAs. Whether implemented via autoregressive token bins, L1 regression, or flow-matching denoising, the resulting decoder treats the action space as unstructured, leaving the geometric proximity of neighboring actions unexploited during training. To advance this, we introduce ActionMap, a voxel heatmap action head that drops into an existing VLA in place of its native action decoder. For each new action, the head predicts a voxel heatmap over the action space, where each voxel directly stores the probability of the corresponding action. Across LIBERO simulation and real-world Franka manipulation, our heatmap head surpasses two architecturally distinct backbones at matched training steps (e.g., +8.2% over OpenVLA-OFT's L1 regression head on the LIBERO four-suite average), converges at comparable or faster rates on both backbones, and remains markedly more data-efficient at low training data. The cross-backbone consistency indicates that action representation is a real lever for VLA performance, distinct from further backbone or recipe scaling. Project Page: https://showlab.github.io/ActionMap/.

09.
bioRxiv (Bioinfo) 2026-06-12

Generalisable tissue-wide molecular reconstruction from histology

Spatial transcriptomics technologies measure gene expression within intact tissues but remain difficult to scale across large tissue sections and patient cohorts. Consequently, many studies rely on tissue microarrays (TMAs) or sparse spatial profiling designs, where molecular measurements are available for only limited tissue regions and are often generated using heterogeneous gene panels. Existing H&E to spatial gene expression prediction methods remain challenged by sparse molecular measurements, partially overlapping gene panels and tissue-wide reconstruction across heterogeneous spatial datasets. Here, we present GHIST+, a framework for tissue-wide reconstruction of single-cell molecular states from H&E histology. GHIST+ integrates cellular morphology, local tissue context and shared tissue representations to extend sparse molecular measurements into tissue-wide molecular maps across heterogeneous spatial datasets. Across multiple cancer types and GTEx breast tissues, GHIST+ reconstructs biologically meaningful tissue-wide molecular organisation from sparse TMA-derived measurements while preserving spatial tissue structure, cell-type organisation and age-associated tissue states across cancer and non-cancer settings. GHIST+ establishes a scalable framework for transforming sparse spatial profiling experiments into tissue-wide molecular maps, enabling cohort-scale molecular reconstruction from routine histology under heterogeneous spatial transcriptomic settings.

10.
Nature (Science) 2026-06-10

A prognostic human brain network for diffuse midline glioma

Authors:

Diffuse midline gliomas (DMGs) are near-universally lethal tumours of the childhood central nervous system1,2. In animal models, DMGs form brain-wide integrated networks through neuron-to-glioma synapses3–6 and glioma-to-glioma gap junctional coupling3. This extensive connectivity robustly promotes the growth and invasion of DMG3–9 and other glial malignancies10–12 through paracrine mechanisms and direct neuron-to-glioma synapses. However, the organization and clinical implications of these connections in the living human brain remain to be elucidated. Here, we develop tumour network mapping to compute the brain-wide connectivity profile of DMG, defining a conserved brain network across pontine and thalamic DMG associated with patient short-term survival (DMG network). Tumour functional connectivity with the DMG network was independently predictive of patient overall survival across two external validation cohorts. Tumour growth mapped to DMG network-specific trajectories and peak in-network neurometabolic changes across development spatiotemporally aligned with the peak age incidence of DMG. Analyses of single-nucleus RNA sequencing data confirmed diverse synaptic gene enrichment in high-connectivity DMG. Strikingly, incidental surgical resection of high-connectivity thalamic DMG tissue conferred a significant survival advantage. Collectively, these data define a conserved and prognostically important brain network in children with DMG, consistent with the hypothesis that DMGs exploit otherwise healthy brain circuits to promote tumour growth. Tumour network mapping of diffuse midline glioma (DMG) defines a conserved and prognostically important brain network in children with DMG, consistent with the hypothesis that DMGs exploit otherwise healthy brain circuits to promote tumour growth.

12.
arXiv (CS.AI) 2026-06-15

Q-Net: Queue Length Estimation via Kalman-based Neural Networks

arXiv:2509.24725v4 Announce Type: replace-cross Abstract: Estimating queue lengths at signalized intersections is a long-standing challenge in traffic management. Partial observability of vehicle flows complicates this task despite the availability of two privacy-preserving data sources: (i) aggregated vehicle counts from loop detectors near stop lines, and (ii) aggregated floating car data (aFCD) that provide segment-wise average speed measurements. However, how to integrate these sources with differing spatial and temporal resolutions for queue length estimation is rather unclear. Addressing this question, we present Q-Net: a queue estimation framework built upon a state-space formulation. This design addresses key challenges in queue modeling, such as violations of traffic conservation assumptions. Q-Net follows the Kalman predict-update structure and maintains physical interpretability in both the state evolution and measurement models. Q-Net uses an AI-augmented Kalman filter to learn time-varying gain dynamics from data. The framework supports real-time implementation and improves spatial transferability by grouping aFCD measurements into fixed-size local groups, making the number of learnable parameters independent of section length. Evaluations on urban main roads in Rotterdam, the Netherlands, show that Q-Net outperforms baseline methods, tracks queue formation and dissipation accurately, and mitigates aFCD-induced delays. By combining data efficiency, interpretability, real-time applicability, and spatial transferability, Q-Net makes accurate queue length estimation possible without costly sensing infrastructure like cameras or radar.

13.
arXiv (CS.LG) 2026-06-12

Physics-Aware Auxiliary Losses Improve Out-of-Distribution Generalization of a GNN Synthesizability Filter

arXiv:2606.12651v1 Announce Type: new Abstract: Machine-learning drug-discovery pipelines increasingly rely on generative models that propose molecules far from the data used to train downstream synthesizability filters. Existing filters (SAScore, SCScore, RAscore, DeepSA) are purely statistical and degrade in exactly this out-of-distribution (OOD) regime. We ask whether cheap, closed-form physical priors, used as auxiliary supervision on a graph neural network (GNN), improve OOD generalization. We add two auxiliary losses to a GINE backbone: a topological complexity regression supervised by the Bertz index, and a strain-energy soft penalty supervised by MMFF94 force-field energy. On a 65,177-molecule corpus (HIV, Tox21, COCONUT) labeled by SAScore thresholds we reproduce a strong in-distribution baseline, then evaluate a 4-way ablation (baseline / +complexity / +strain / +both) on a single-source OOD split (train on drug-like HIV+Tox21, test on COCONUT natural products), repeated over 5 seeds with paired bootstrap confidence intervals. All three physics-aware variants give a small but statistically significant OOD improvement over the baseline (mean OOD AUC 0.9774): +complexity Delta = +0.0060 (95% CI [+0.0023, +0.0102]), +strain Delta = +0.0032 ([+0.0008, +0.0052]), +both Delta = +0.0066 ([+0.0038, +0.0093]); every interval excludes zero, and the combination is best. The variants are indistinguishable in-distribution, so the effect is visible only under OOD evaluation. We are explicit that the effects are modest, and we report a cautionary methodological finding: a single-seed version of this experiment produced a qualitatively different (non-monotone) story that did not survive multi-seed evaluation.

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

ReAge3D: Re-Aging 3D Faces with View Consistency

We present a novel framework for realistic and controllable 3D face re-aging which produces highly detailed, identity-preserving results. Existing 3D editing methods, while effective for coarse semantic changes, are not well suited for re-aging, as even small inconsistencies across re-aged 2D views can lead to over-smoothing of subtle but perceptually important age-related details. To address this challenge, we first introduce a 2D diffusion-based re-aging model, DiffReaging, trained on synthetically generated image pairs. We further propose a center-out editing propagation strategy that leverages this re-aging model to reconstruct multi-view-consistent re-aged images. Specifically, starting from a re-aged frontal pivot view, we reconstruct the remaining views through warping and our proposed Masked-DiffReaging process. By injecting existing content at every step of the diffusion process, Masked-DiffReaging ensures that the reconstructed regions remain coherent with existing pixels. The resulting consistent set of re-aged views supervises the optimization of the re-aged 3D representation. Our method outperforms existing 3D editing techniques both visually and quantitatively, enabling smooth, fine-grained control over age transformations in 3D face models.

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

Position: The Systemic Lack of Agency in Visual Reasoning

This paper argues that a systemic lack of Agency constrains the implicit reasoning capabilities of current Vision-Language Models (VLMs). Implicit reasoning refers to the ability to autonomously discover and utilize hidden visual evidence to bridge information gaps, rather than merely relying on explicitly specified targets. This capacity underlies human visual understanding and everyday reasoning. We argue that this limitation arises from a tendency to approach visual reasoning primarily as passive semantic retrieval, rather than as active, situated reasoning that depends on autonomous visual exploration. As a result, most existing benchmarks primarily assess Passive Capacity, leaving this aspect of reasoning largely unmeasured. To address this gap, we introduce the Visual Implicit Reasoning Diagnosing Benchmark (V-IRD), which targets this missing quadrant by requiring models to derive answers strictly through autonomous visual analysis. Our results show that, despite strong retrieval abilities, prominent VLMs struggle to utilize reference objects and to attend to visual evidence that requires self-directed inquiry. Simply put, strong semantic recognition does not equate to active visual exploration, revealing a critical gap in current VLMs. More information can be found at https://haoychen.github.io/Implicit-Reasoning/

16.
arXiv (math.PR) 2026-06-12

Voronoi Percolation: Topological Stability and Giant Cycles

arXiv:2601.00793v2 Announce Type: replace Abstract: We study the topological stability of Voronoi percolation in higher dimensions. We show that slightly increasing p allows a discretization that preserves increasing topological properties with high probability. This strengthens a theorem of Bollobás and Riordan and generalizes it to higher dimensions. As a consequence, we prove a sharp phase transition for the emergence of i-dimensional giant cycles in Voronoi percolation on the 2i-dimensional torus.

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

A Neuromorphic Reinforcement Learning Framework for Efficient Pathfinding in Robotic Mobile Fulfillment Systems

arXiv:2606.20031v1 Announce Type: cross Abstract: Dynamic environmental changes, confined workspaces, and stringent real-time constraints make pathfinding in Robotic Mobile Fulfillment Systems (RMFS) a challenging problem for conventional search- and rule-based methods, which typically suffer from high computational complexity and long decision latency. While reinforcement learning (RL) has emerged as a powerful alternative, deploying learned policies with extreme energy efficiency on resource-constrained hardware remains an open challenge. We present SDQN-RMFS, an end-to-end framework that achieves high-fidelity deployment of an RL-trained policy from a full-precision artificial neural network (ANN) through to a neuromorphic chip. By computing only when triggered by sparse events, this framework unlocks ultra-low-power RMFS pathfinding. Our full-stack pipeline operates as follows: an ANN policy is first efficiently trained via a collision-allowing strategy to densify informative trajectories, and then converted into a spiking neural network (SNN) via a hard-label knowledge distillation approach. This effectively addresses the output distribution mismatch, preserving policy capability across the ANN-to-SNN pipeline while substantially reducing inference latency. Hardware experiments demonstrate up to 11,281$\times$ energy savings and a nearly two-fold reduction in latency compared to a high-performance GPU baseline, while maintaining decision quality on par with the original trained policy. These results establish physical neuromorphic inference as a practical and energy-sustainable pathway for large-scale RMFS operations.

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

Structuring The Future: Diffusion LLM Speculative Decoding via Calibrated Draft Graphs

Diffusion LLMs (dLLMs) have recently emerged as a powerful alternative to autoregressive LLMs (AR-LLMs) with the potential to operate at significantly higher token-generation rates. To unlock this potential, we present Spiffy, a speculative decoding algorithm to accelerate dLLM inference while provably preserving the model's output distribution. This work addresses the unique challenges involved in applying ideas from speculative decoding of AR-LLMs to dLLMs. Spiffy performs auto-speculation to eliminate the overheads of an independent draft model, structuring draft states in the form of a novel directed draft graph to take advantage of the bidirectional, blockwise nature of dLLM generation. These draft graphs are calibrated offline to maximize acceptance rates and are dynamically pruned during inference for improved computational efficiency. We present a detailed formulation of Spiffy and demonstrate its ability to accelerate LLaDA, Dream, and SDAR models in combination with KV caching and threshold-based dynamic unmasking leading to up to $8.6\times$ reduction in model inferences and $6.3\times$ acceleration in token rate.

19.
arXiv (CS.LG) 2026-06-16

HRIR-Former: Grid-Free Time-Domain Reconstruction of Head-Related Impulse Responses with a Spatially Encoded Transformer

arXiv:2603.27998v2 Announce Type: replace-cross Abstract: Individualized head-related impulse responses (HRIRs) enable binaural rendering, but dense per-listener measurements are costly. We address HRIR spatial up-sampling from sparse per-listener measurements: given a few measured HRIRs for a listener, predict HRIRs at unmeasured target directions. Prior learning methods often work in the frequency domain, rely on minimum-phase assumptions or separate timing models, and use a fixed direction grid, which can degrade temporal fidelity and spatial continuity. We propose HRIR-Former, a time-domain, grid-free binaural Transformer for reconstructing HRIRs at arbitrary directions from sparse inputs. It uses sinusoidal spatial features, a Conv1D refinement module, and auxiliary interaural time difference (ITD) and interaural level difference (ILD) heads. On SONICOM, it improves normalized mean squared error (NMSE), cosine distance, and ITD/ILD errors over prior methods; ablations validate modules and show minimum-phase preprocessing is unnecessary.

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

Self-Distillation Zero: Self-Revision Turns Binary Rewards into Dense Supervision

Current post-training methods in verifiable settings fall into two categories. Reinforcement learning (RLVR) relies on binary rewards, which are broadly applicable and powerful, but provide only sparse supervision during training. Distillation provides dense token-level supervision, typically obtained from an external teacher or using high-quality demonstrations. Collecting such supervision can be costly or unavailable. We propose Self-Distillation Zero (SD-Zero), a method that is substantially more training sample-efficient than RL and does not require an external teacher or high-quality demonstrations. SD-Zero trains a single model to play two roles: a Generator, which produces an initial response, and a Reviser, which conditions on that response and its binary reward to produce an improved response. We then perform on-policy self-distillation to distill the reviser into the generator, using the reviser's token distributions conditioned on the generator's response and its reward as supervision. In effect, SD-Zero trains the model to transform binary rewards into dense token-level self-supervision. On math and code reasoning benchmarks with Qwen3-4B-Instruct and Olmo-3-7B-Instruct, SD-Zero improves performance by at least 10% over the base models and outperforms strong baselines, including Rejection Fine-Tuning (RFT), GRPO, and Self-Distillation Fine-Tuning (SDFT), under the same question set and training sample budget. Extensive ablation studies show two novel characteristics of our proposed algorithm: (a) token-level self-localization, where the reviser can identify the key tokens that need to be revised in the generator's response based on reward, and (b) iterative self-evolution, where the improving ability to revise answers can be distilled back into generation performance with regular teacher synchronization. Code: https://github.com/princeton-pli/Self-Distillation-Zero.

21.
bioRxiv (Bioinfo) 2026-06-16

AutoZyme: An Autonomous Agentic Framework to Optimize Bioinformatics Software

Performance bottlenecks in widely used genomics and bioinformatics software present a substantial and growing burden as biological datasets continue to increase in size and number. Relieving these bottlenecks relies largely on expert manual optimization and therefore remains difficult to scale. Here we present AutoZyme, an agentic framework for scientific software optimization. Given a target function, AutoZyme builds benchmarks, identifies bottlenecks, and iteratively tests code changes, retaining only those that improve runtime while preserving output. We evaluated AutoZyme on 45 functions, improving runtime without substantial memory increases in over 95% of cases considered. Across 38 functions from Seurat, Scanpy and related packages in genomics and bioinformatics, AutoZyme reduced runtime by a median of 8.52-fold, with the largest reductions exceeding 676-fold. The optimized functions are distributed through AutoZyme-Library as drop-in replacements for existing analysis pipelines. We also release AutoZyme as a reusable framework for optimizing additional user-specified packages and functions.

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

PhyloSDF: Phylogenetically-Conditioned Neural Generation of 3D Skull Morphology via Residual Flow Matching

Generating novel, biologically plausible three-dimensional morphological structures is a fundamental challenge in computational evolutionary biology, hampered by extreme data scarcity and the requirement that generated shapes respect phylogenetic relationships among species. In this work, we present PhyloSDF, a phylogenetically-conditioned neural generative model for 3D biological morphology that integrates two innovations: (1) a DeepSDF auto-decoder regularized by a novel Phylogenetic Consistency Loss that structures the latent space to correlate with evolutionary distances (Pearson r=0.993); (2) a Residual Conditional Flow Matching (Residual CFM) architecture that factorizes generation into analytic species-centroid lookup and learned residual prediction, enabling generation from as few as ~4 specimens per species. We evaluate PhyloSDF on 100 micro-CT-scanned skulls of Darwin's Finches and their relatives across 24 species. The model generates novel meshes achieving 88-129% of real intra-species variation at the code level, with all 180 generated meshes verified as non-memorized. Residual CFM surpasses denoising diffusion (which fails entirely at this scale), standard flow matching (which mode-collapses to 3-6% variation), and a Gaussian mixture baseline in both fidelity (Chamfer Distance 0.00181 vs. 0.00190) and morphometric Fr\'{e}chet distance (10,641 vs. 13,322). Leave-one-species-out experiments across 18 species demonstrate phylogenetic extrapolation capability, and smooth latent interpolations produce biologically plausible ancestral skull reconstructions.

23.
bioRxiv (Bioinfo) 2026-06-18

Bioinf-Farma: supervised integration of epitope prediction and recombinant protein developability for automated vaccine candidate prioritization

Vaccine antigen discovery requires prioritizing protein candidates according to both immunogenic potential and recombinant expression feasibility. These properties are typically evaluated using separate computational tools, requiring researchers to integrate heterogeneous outputs through ad hoc workflows. Here, we present BIOINF-farma, a modular platform integrating epitope prediction and developability assessment for rational antigen selection within a unified environment. Candidates can be submitted as amino acid sequences or three-dimensional structures. When experimental structures are unavailable, BIOINF-farma automatically searches for models in AlphaFold DB or performs structure prediction using Boltz-2, ensuring a standardized structural representation for downstream analyses. Antigenicity is quantified by combining structure-based conformational epitope signals (MLCE/REBELOT-BEPPE) and sequence-based linear epitope propensity scores (BepiPred 3.0) into a protein-level Antigenicity Score, with a classification threshold optimized on a manually curated validation dataset. Developability is evaluated through two supervised Random Forest meta-learners that integrate three solubility predictors (DeepSoluE, SoluProt, Protein-Sol) and three thermal stability predictors (TemStaPro, ProLaTherm, BertThermo), whose outputs are combined into an Expression Efficiency Score (EES). By integrating complementary predictive signals, the meta-learning framework achieves greater accuracy and robustness than individual predictors while maintaining performance across a broad range of sequence identities. The Antigenicity Score effectively discriminates antigenic from non-antigenic proteins with a large effect size, whereas EES successfully distinguishes soluble from insoluble outcomes on an independent panel of recombinant proteins expressed in Escherichia coli. BIOINF-farma jointly assesses antigenicity and expression feasibility within a single framework. Its modular architecture facilitates the incorporation of future predictive methods, while its web-based interface makes the full pipeline accessible to users without programming expertise, supporting rapid candidate triage in vaccine research and emerging pathogen responses.

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

From Argument Components to Graphs: A Multi-Agent Debate with Confidence Gating for Argument Relations

Large Language Models (LLMs) are increasingly assessed and utilized in the field of Argument Mining (AM), thanks to their strong general reasoning capabilities. However, standard training-free models often miss sophisticated details, specifically in contexts where two parts of the text have to be analyzed together. Furthermore, self-correction mechanisms tend to reinforce initial hallucinations in reasoning. Overcoming these limitations typically requires expensive, domain-specific supervised fine-tuning. Recent work has shown that a multi-agent paradigm can address such weaknesses for the component classification task through dialectical refinement with a Proponent-Opponent-Judge architecture, setting a promising direction for training-free approaches in the field. In this paper, we extend and evaluate this framework on the Argument Relation Identification and Classification (ARIC) task, reformulating it as a debate over component pairs. Besides that, we introduce a confidence gating mechanism that enables debating only on the uncertain cases and accepting the initial prediction when confidence is high. On the UKP Argument Annotated Essays v2 corpus, we demonstrate that the selective debate achieves the highest Macro F1 among all training-free methods, while debate over all samples degrades performance below that of one of the baselines. All generative approaches also outperform fine-tuned RoBERTa models on Macro F1, suggesting that the under-representation of the Attack class was more damaging to supervised fine-tuning than to inference-only models. Additionally, our framework produces human-readable debate transcripts, offering interpretability absent from both single-agent and supervised classifiers.

25.
bioRxiv (Bioinfo) 2026-06-11

PhyloZoo: a unified framework for phylogenetic network analysis in Python

Authors:

Reticulate evolutionary processes (events in which lineages merge, such as hybridization, recombination, and horizontal gene transfer) are widespread across nature but cannot be represented by phylogenetic trees alone. Phylogenetic networks have therefore become an important modelling tool, yet existing software is typically tied to specific inference paradigms and provides limited support for working with multiple network representations in a unified and programmable environment. PhyloZoo is an open-source Python framework that lowers the barrier to developing practical, easy-to-use software for phylogenetic network analysis. It provides data structures and algorithms covering the main representations used in the field, together with dedicated visualization tools and robust I/O for all major phylogenetic file formats. A particular emphasis lies on semi-directed phylogenetic networks, which explicitly represent root uncertainty and have so far received limited support in existing software. By offering a shared foundation for developing interoperable tools and a combinatorial layer that supports computational proofs and theoretical exploration, PhyloZoo enables reproducible workflows for applied, methodological, and theoretical studies of reticulate evolution. Availability and implementation: PhyloZoo is implemented in Python and installable from PyPI, with source code, documentation, and examples available at https://github.com/nholtgrefe/phylozoo.