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01.
arXiv (CS.CV) 2026-06-17

HRDX: A Large-Scale Vector HD-Map Dataset

Reliable autonomous driving requires vectorized HD maps that are geometrically accurate, semantically rich, and scalable to long-horizon driving. However, existing public HD map datasets are limited in scale, provide sparse semantic attributes, and lack modalities such as aerial imagery that could enable new research directions. We present HRDX, a large-scale dataset for vector HD-map construction, spanning about 40 hours (1,400 km) of minimally overlapping drives, which is several times larger than prior public HD map datasets. Data is captured using six synchronized surround cameras, a 128-beam LiDAR, and centimeter-level RTK GNSS/IMU, and is further complemented by precisely aligned aerial orthoimagery. Annotations cover 10 vector map classes, complemented with over 20 semantic and topological attributes. To evaluate this richer ontology, we introduce the Composite Score (CS) to jointly assess geometric fidelity and attribute correctness. Benchmark experiments show that HRDX's scale improves online vector-map construction, and that aligned aerial imagery provides a useful structural prior: using aerial imagery at training and/or inference improves geometric map quality, while aerial-augmented teachers can transfer part of this benefit to camera-only students without increasing inference-time sensor requirements. HRDX is intended to support reproducible research on large-scale HD-map learning, multimodal BEV fusion, and training-time privileged information. HRDX dataset and benchmarks are available at https://github.com/honda-research-institute/HRDX

02.
bioRxiv (Bioinfo) 2026-06-10

GEOAgent: An AI-driven Autonomous Framework for Intelligent GEO Data Retrieval and Standardized Preprocessing

Datasets in the Gene Expression Omnibus (GEO) remain difficult to reuse at scale because sample annotations are heterogeneous and raw sequencing data require assay-specific preprocessing. We present GEOAgent, an AI-driven autonomous framework designed for intelligent dataset retrieval and standardized preprocessing by coupling autonomous semantic governance with an automated Nextflow pipeline named bioStream. Metadata from 181,760 sequencing series and 84,756 associated PubMed records were organized in a relational database and semantic index to support natural-language dataset retrieval. The framework automatically determines assay modalities, resolves experimental design pairings, and standardizes sample naming to minimize manual curation overhead. Based on these parsed attributes, the framework generates deployment-ready manifests to automatically execute containerized workflows across bulk and single-cell omics modalities. In expert-curated benchmarks, the workflow achieved 96% retrieval precision alongside 100% accuracy in assay classification and sample relationship resolution. The web platform is publicly accessible, while the source code and associated databases are openly available via GitHub and Zenodo.

03.
arXiv (quant-ph) 2026-06-12

Supersymmetry of dissipative Bose-Fermi systems with application to Jaynes-Cummings and Dicke models

arXiv:2606.12682v1 Announce Type: new Abstract: We demonstrate how supersymmetries of Hamiltonians for coupled Bose-Fermi systems can be used to place the Hamiltonians of the Jaynes-Cummings model and Dicke model under the rotating wave approximation in matrix form and provide explicit analytic solutions for their eigenvalues. We then use this supersymmetry to place the Liouvillians of the associated Markovian open systems in matrix form and provide explicit solutions for their eigenvalues. These results are a consequence of the fact that the Hamiltonian of the Jaynes-Cummings model commutes with the linear Casimir invariant of the superalgebra $u(1|1)$ and that the Hamiltonian of the Dicke model commutes both with the linear invariant of $\sum_{i} u_{i}(1|1)$ and with the invariant of an additional $su(2)$ algebra. Our methods apply to various coupled Bose-Fermi systems with $u(1|1)$ and more generally with $u(n|m)$ dynamical superalgebras, and may provide efficient tools for studying more complicated examples.

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

Distributionally Robust Set Representation Learning Under Inference-Time Element Corruption

arXiv:2605.30089v2 Announce Type: replace Abstract: Standard Set Representation Learning methods typically excel on curated data but often overlook the challenge of inference-time element corruption. This refers to scenarios where deployed models encounter element-level degradations, such as outliers or missing components, that may distort set representation and degrade performance. We propose SW-DRSO, a distributionally robust optimization framework tailored for sets. Rather than minimizing loss solely on observed training data, SW-DRSO optimizes a tractable surrogate of the worst-case expected loss over a family of plausible inference-time variations. We introduce a barycentric adversary that approximates the intractable search over corrupted sets by a differentiable training-time optimization over simplex weights. Extensive experiments across four tasks demonstrate that SW-DRSO effectively enhances robustness against corruption while maintaining high overall performance.

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

E2Vec: Feature Embedding with Temporal Information for Analyzing Student Actions in E-Book Systems

Digital textbook (e-book) systems record student interactions with textbooks as a sequence of events called EventStream data. In the past, researchers extracted meaningful features from EventStream, and utilized them as inputs for downstream tasks such as grade prediction and modeling of student behavior. Previous research evaluated models that mainly used statistical-based features derived from EventStream logs, such as the number of operation types or access frequencies. While these features are useful for providing certain insights, they lack temporal information that captures fine-grained differences in learning behaviors among different students. This study proposes E2Vec, a novel feature representation method based on word embeddings. The proposed method regards operation logs and their time intervals for each student as a string sequence of characters and generates a student vector of learning activity features that incorporates time information. We applied fastText to generate an embedding vector for each of 305 students in a dataset from two years of computer science courses. Then, we investigated the effectiveness of E2Vec in an at-risk detection task, demonstrating potential for generalizability and performance.

07.
arXiv (CS.LG) 2026-06-18

JourneyFormer: Encoding Airbnb Guest Journey with Sequence Modeling

arXiv:2606.19108v1 Announce Type: new Abstract: Sequence modeling has become increasingly popular in recommendation and ranking algorithms, owing to its capacity to model users' historical behaviors and infer user intentions. Despite its theoretical simplicity, the practical deployment of a sequence model in production is non-trivial due to complexity of the sequence and sparse labels. For example, in Airbnb, guest sequences are often long, exploratory and complex, and we focus on booking labels, which are sparse. As such, we are often required to make various design decisions regarding data and modeling to strike a balance between effectiveness and scalability. This work delved into these production challenges and deployed JourneyFormer, a sequence modeling solution for search ranking at Airbnb. We detail crucial design considerations, covering aspects such as guest event selection, ID embeddings, model architecture, and label attribution. Additionally, we describe several tailored strategies to accelerate model training and inference. JourneyFormer has been successfully deployed within Airbnb's production, where its effectiveness and impact have been evidenced not only by improved offline ranking metrics but also by significant gains in key business metrics through online A/B testing across 2 production surfaces.

08.
arXiv (math.PR) 2026-06-16

Logarithmic Large Deviations for Heavy-Tailed Sums

arXiv:2606.16487v1 Announce Type: new Abstract: We establish logarithmic large-deviation bounds for sums of independent nonnegative random variables with regularly varying tails. The normalization is chosen at the extreme-value scale and the speed is $\log n$. In contrast with Cramér's theorem, the resulting rate function is determined only by the tail index. The proof transfers a maximum large-deviation principle to sums in the one-big-jump region.

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

A Multi-Agent AI System for Automated High School Transcript Processing: Collaborative Document Analysis at Scale

arXiv:2606.13916v1 Announce Type: new Abstract: Each year, college admissions offices face an overwhelming challenge: processing millions of high school transcripts, each with unique formats, grading systems, and layouts. This manual process creates operational bottlenecks that delay admissions decisions and consume valuable resources. We present a transformative solution through a multi-agent AI system where specialized agents collaborate to automatically process diverse transcript formats through intelligent coordination and communication. Our multi-agent architecture consists of three specialized agents-a Pattern Recognition Agent for format-specific parsing, a Semantic Analysis Agent for natural language understanding, and a Vision Intelligence Agent for multimodal document analysis-coordinated by an Orchestration Agent that manages agent communication and result reconciliation. Our key innovation lies in agent-based quality control using GPA extraction as a coordination signal, ensuring reliable agent collaboration and preventing critical information loss. When evaluated on 40 real world transcripts from high schools across 13 U.S. states, our agent system successfully processed every document, achieving 96.7% accuracy compared to expert manual review while maintaining practical processing speeds of 45 seconds per transcript. This work demonstrates how multi-agent coordination can solve complex document processing challenges, offering institutions a scalable, collaborative AI solution that preserves accuracy while dramatically reducing processing time.

10.
arXiv (quant-ph) 2026-06-17

Unclonable Encryption in the Haar Random Oracle Model

arXiv:2603.11437v2 Announce Type: replace-cross Abstract: We construct unclonable encryption (UE) in the Haar random oracle model, where all parties have query access to $U,U^\dagger,U^*,U^T$ for a Haar random unitary $U$. Our scheme satisfies the standard notion of unclonable indistinguishability security, supports reuse of the secret key, and can encrypt arbitrary-length messages. That is, we give the first evidence that (reusable) UE, which requires computational assumptions, exists in "microcrypt", a world where one-way functions may not exist. As one of our central technical contributions, we build on the recently introduced path recording framework to prove a natural ``unitary reprogramming lemma'', which may be of independent interest.

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

Circuit Synchronization Precedes Generalization: Causal Evidence from Fourier Structure in Grokking Transformers

arXiv:2606.12966v1 Announce Type: new Abstract: Grokking – where a transformer on modular arithmetic suddenly transitions from near-chance to near-perfect validation accuracy – is attributed to a Fourier circuit, but its timing, causal structure, and controllability remain poorly understood. We introduce the Frequency Synchronization Degree (FSD), a normalised, permutation-tested metric for Fourier circuit synchronisation requiring no prior circuit knowledge. Across nine modular addition configurations (primes p in {53, 71, 97, 113, 131}, three seeds), FSD synchronises 500-3,000 steps before grokking (mean lead +1,722 steps; all nine positive, sign-test p~0.004), and precedes a restricted-logit loss baseline (Nanda et al.'s excluded loss) in all nine cases, making it the earliest available predictor. We provide direct causal evidence that the inter-phase gap is a regularisation phenomenon: forking training at the FSD-ceiling step and varying weight decay lambda produces strictly monotone earlier grokking, with Delta_t proportional to 1/lambda. This law replicates across three primes (p in {53,97,131}; R^2=1.00 and R^2=0.99 for two clean cases), captured as Delta_t ~ C/lambda, consistent with (1/lambda)*log(||W_mem||/tau). Architecture ablations show an attention-only model groks with a strong FSD precursor; an MLP-only model never groks; a single-layer model's FSD lags, confirming the precursor is a multi-block circuit property.

12.
medRxiv (Medicine) 2026-06-16

Re-evaluating the Cross-Sectional Prevalence of Severe Age-Related Hearing Loss Using Extreme Value Statistics

Authors:

Standard demographic models of age-related hearing loss (presbycusis) predominantly utilize symmetric functions, such as log-normal distributions for age-binned thresholds and 4-parameter logistic curves for prevalence estimates. While these models capture early-to-moderate degradation effectively, they structurally struggle to characterize the heavy tails associated with severe clinical impairment. In this study, we present a statistical critique using a secondary analysis of the historical Medical Research Council (MRC) National Study of Hearing (1980-1986) dataset. By applying Generalized Extreme Value (GEV) distribution theory, we demonstrate that as severity increases, the underlying statistical geometry of hearing loss shifts. The asymmetric, heavy-tailed GEV distribution provides a parsimonious description of severe impairment, requiring fewer parameters than standard symmetric models. However, we explicitly acknowledge that utilizing static population data to infer progression introduces an ecological fallacy. Furthermore, the dataset's historical nature embeds unquantified generational cohort effects. We conclude that while extreme value statistics offer a compelling mathematical framework for modeling the variance of severe presbycusis, true longitudinal datasets are required to isolate physiological degradation from historical cohort variance.

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

Measuring Control-Plane Openness in Near-Term Quantum Computing: A Rubric, Its Validation, and an Application to Thirteen Vendor Stacks

arXiv:2605.15233v2 Announce Type: replace Abstract: Public access to pulse-level and control-electronics interfaces in commercial quantum computing has bifurcated. This paper proposes a six-axis rubric for measuring control-plane openness, the layer between gate-level circuit specification and physical control electronics, defined operationally so that the same evidence produces the same grade across vendors. The rubric is validated three ways: a blinded re-grading pass, thirty-nine days after the evidence cutoff, that tests whether the cited evidence and the level definitions alone reproduce the recorded grades; a boundary-case methodology that fixes where each level begins and ends; and a published grading protocol that lets others reproduce and contest any cell. We establish that the rubric measures change rather than describing a snapshot by comparing the catalog against the documented control plane before the February 2025 removal of pulse-level access from IBM hardware, and reporting the cells that moved. The rubric is applied to thirteen commercial vendors across superconducting, trapped-ion, neutral-atom, and photonic modalities as of May 1, 2026, as its first application, and one of the three harms the rubric is designed to detect is demonstrated through a reproduction-access audit of five pre-2025 IBM Qiskit Pulse experiments against the access available on current hardware, carried through to a client-side structural port of the audit's selected target to Rigetti Quil-T. The catalog ships as a separate machine-readable artifact under CC-BY-4.0 with per-cell source URLs (https://doi.org/10.5281/zenodo.20163276). The catalog readings will change as vendor policies shift; the rubric is the contribution that survives them.

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

FinAcumen: Financial Multimodal Reasoning via Self-Evolving Experience Memory Harness

arXiv:2606.17642v1 Announce Type: new Abstract: Financial multimodal reasoning requires agents to coordinate numerical computation, retrieval, visual interpretation, and temporal grounding across heterogeneous evidence sources. Existing tool-augmented agents improve execution fidelity, yet remain largely stateless across episodes, repeatedly rediscovering reasoning strategies and failure patterns. In high-stakes financial settings, this leads to unreliable tool routing, noisy retrieval, and hallucination-prone reasoning. We present FinAcumen, a financial reasoning agent framework centered on selective experience memory for tool-augmented multimodal reasoning. FinAcumen accumulates financially grounded reasoning experience from prior trajectories, distilling successful strategies and failure-derived cautionary rules into a persistent memory bank. During inference, retrieved experiences condition reasoning only when semantic relevance exceeds a calibrated threshold, while irrelevant memory is explicitly suppressed through a fallback mechanism. A deterministic financial tool environment further grounds numerical computation, retrieval, visual decoding, and answer verification.Across four financial multimodal reasoning benchmarks, FinAcumen consistently improves a frozen 8B vision-language model over finance-specialized models and approaches leading proprietary general-purpose models. Further analysis shows that selective experience activation improves reasoning reliability under retrieval uncertainty. Our code is anonymously available at https://anonymous.4open.science/r/FinAcumen

15.
arXiv (math.PR) 2026-06-16

Delayed acceptance sampling with Hamiltonian proposal subchains for random field materials inference

arXiv:2606.14743v1 Announce Type: cross Abstract: This paper focuses on accelerating Markov chain Monte Carlo sampling in Bayesian inverse problems in which forward model evaluations dominate the computational cost. It builds on several established ingredients previously used in related scenarios: delayed acceptance, neural network surrogate models, Hamiltonian proposals, and proposal subchains. The main framework is the delayed-acceptance Metropolis-Hastings algorithm of Christen and Fox (2005). The first-stage proposal distribution is constructed from a subchain of Hamiltonian trajectories targeting the surrogate posterior. For each fixed surrogate model, the Hamiltonian subchain and delayed-acceptance correction define a kernel invariant with respect to the exact posterior. In the present work, the surrogate is updated only during a burn-in phase, after which the production run uses a fixed surrogate model. The sampling framework is implemented in Python using parallel processes. Several chains are generated in parallel and share a single surrogate model trained during burn-in on all collected data. The forward model is treated as a black box; therefore, the application area is broad. However, the main motivation is efficient solution of geotechnical inverse problems with material properties represented by Gaussian random fields. In this study, the sampling framework is applied to a geotechnical inverse problem in which hydraulic conductivity and porosity are modeled as non-stationary Gaussian random fields approximated using truncated Karhunen-Loeve expansions. Based on a precomputation, the truncation dimensions are chosen separately for hydraulic conductivity and porosity. The forward model outputs are pore pressure values at control points and selected observation times. These are compared with in situ pore pressure measurements collected over one year during the Tunnel Sealing Experiment in an underground laboratory in Canada.

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

SIGMA: Search-Augmented On-Demand Knowledge Integration for Agentic Mathematical Reasoning

Solving mathematical reasoning problems requires not only accurate access to relevant knowledge but also careful, multi-step thinking. However, current retrieval-augmented models often rely on a single perspective, follow inflexible search strategies, and struggle to effectively combine information from multiple sources. We introduce SIGMA (Search-Augmented On-Demand Knowledge Integration for AGentic Mathematical reAsoning), a unified framework that orchestrates specialized agents to independently reason, perform targeted searches, and synthesize findings through a moderator mechanism. Each agent generates hypothetical passages to optimize retrieval for its analytic perspective, ensuring knowledge integration is both context-sensitive and computation-efficient. When evaluated on challenging benchmarks such as MATH500, AIME, and PhD-level science QA GPQA, SIGMA consistently outperforms both open- and closed-source systems, achieving an absolute performance improvement of 7.4%. Our results demonstrate that multi-agent, on-demand knowledge integration significantly enhances both reasoning accuracy and efficiency, offering a scalable approach for complex, knowledge-intensive problem-solving. We will release the code upon publication.

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

Observation of alignment tensor effects in metastability-exchange collisions with highly polarized 3He ensembles

arXiv:2606.20330v1 Announce Type: new Abstract: Highly polarized 3He ensembles prepared by metastability-exchange optical pumping (MEOP) have been widely used in precision measurements and fundamental physics. Metastability-exchange (ME) collisions, serving as the basis of MEOP, are traditionally described in terms of atomic orientation, while the significant contributions of metastable alignment tensor at high polarization remain unexplored. In this work, we develop a linearized model under mean-field approximation to investigate alignment tensor effects in highly polarized 3He , which originate from the metastable F = 3/2 manifold and are revealed through ME-induced relaxation and frequency shift. By means of free-induction-decay (FID) measurements, a pronounced dependence on nuclear polarization is experimentally observed in the response of the ground-state-metastable hybrid 3He ensembles to the external magnetic field. Furthermore, after obtaining the characteristics of tensor-induced phenomena, we demonstrate good agreement between the experiment and the theory. This work advances the understanding of nuclear spin dynamics in highly polarized 3He using MEOP. It further provides applications in systematic error correction of high-accuracy magnetometry, as well as in optimal protocol for the generation of nuclear spin-squeezed states.

18.
arXiv (CS.CV) 2026-06-19

Does Head Pose Correction Improve Biometric Facial Recognition?

Biometric facial recognition models often demonstrate significant decreases in accuracy when processing real-world images, often characterized by poor quality, non-frontal subject poses, and subject occlusions. We investigate whether targeted, AI-driven, head-pose correction and image restoration can improve recognition accuracy. Using a model-agnostic, large-scale, forensic-evaluation pipeline, we assess the impact of three restoration approaches: 3D reconstruction (NextFace), 2D frontalization (CFR-GAN), and feature enhancement (CodeFormer). We find that naive application of these techniques substantially degrades facial recognition accuracy. However, we also find that selective application of CFR-GAN combined with CodeFormer yields meaningful improvements.

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

Characterizing Cultural Localization in AI-Generated Stories

The global use of artificial intelligence has increased interest in assessing the ability to generate culturally localized content, including stories. Cultural localization in stories often occurs through either templated localization – the use of cultural markers (e.g., names, locations) in a generic narrative – or holistic localization – the variation of plots, values, and themes, in addition to cultural markers. We propose a method to measure the degree to which content was generated through templated localization. Specifically, we identify the lexical tokens that distinguish stories across nationalities and measure the similarity of the narratives that remain after removing them. In stories generated by five models on 125 topics for 193 nationalities, our method is able to detect that only a small subset (9-17%) of the vocabulary accounts for the variation across nationalities and that the narratives that remain after removing them contain repeated multi-word sequences, suggesting the presence of a shared culturally-agnostic narrative template. Finally, we characterize the cultural markers for their stereotypicality and offensiveness, finding that markers from 19 countries, mostly located in the Global South, are on average offensive.

20.
arXiv (math.PR) 2026-06-16

Steady-State Approximation Error of Heterogeneous Mean-Field Models

Authors:

arXiv:2606.09022v2 Announce Type: replace Abstract: This paper studies heterogeneous mean-field models in which agent parameters are sampled from a population distribution. We establish an $O(1/M)$ bound on the steady-state mean-square error between the occupancy measure of the $M$-agent system and the corresponding annealed mean-field equilibrium. The analysis extends Stein's method for homogeneous mean-field models and reveals a fundamental difference between homogeneous and heterogeneous systems. While stability of the mean-field dynamics is sufficient in the homogeneous setting, heterogeneous systems further require uniform robustness of the occupancy dynamics with respect to perturbations of the initial condition. The results are illustrated through a heterogeneous SIS epidemic model.

21.
arXiv (CS.LG) 2026-06-12

When Does Routing Become Interpretable? Causal Probes on Block Attention Residuals

Authors:

arXiv:2606.13168v1 Announce Type: new Abstract: Block Attention Residuals (Block AttnRes) by replace fixed additive residuals with a learned softmax over earlier depth-source representations, surfacing cross-layer routing as an inspectable tensor in the forward pass. This is a tempting interpretability target: information flow normally inferred indirectly is now directly observable. We ask whether such exposure suffices for mechanistic interpretation. We probe two same-scale ($0.6$B) Block AttnRes checkpoints under identical routing-ablation interventions: a vanilla Qwen3 inference-wrapped through a deterministic recency-bias schedule that the codebase admits as a routing-equivalent loading path, and a Block AttnRes Qwen3 trained from scratch with routing as part of optimisation. The wrapped baseline's routing weights are content-independent and reproduce the schedule's analytic prediction. The trained AttnRes checkpoint instead exhibits three localised routing motifs: an embedding-source pathway through early-layer MLP, a current-state pathway through early-layer attention and MLP, and an older-history pathway through late-layer attention. Beyond this stratification, we find a sharp dissociation between average routing mass and causal importance: in both sublayers, the largest mass slice is not the largest causal contribution, and one source family carries appreciable mass with no detectable causal role under intervention. Architectural exposure of routing is therefore necessary but not sufficient for mechanistic interpretation: structured depth routing emerges only when routing has been part of training, and even then, descriptive routing summaries should be treated as candidate hypotheses to be tested by causal interventions, not as evidence of mechanism in their own right.

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

DPC-VQA: Decoupling Quality Perception and Residual Calibration for Video Quality Assessment

Recent multimodal large language models (MLLMs) have shown promising performance on video quality assessment (VQA) tasks. However, adapting them to new scenarios remains expensive due to large-scale retraining and costly mean opinion score (MOS) annotations. In this paper, we argue that a pretrained MLLM already provides a useful perceptual prior for VQA, and that the main challenge is to efficiently calibrate this prior to the target MOS space. Based on this insight, we propose DPC-VQA, a decoupling perception and calibration framework for video quality assessment. Specifically, DPC-VQA uses a frozen MLLM to provide a base quality estimate and perceptual prior, and employs a lightweight calibration branch to predict a residual correction for target-scenario adaptation. This design avoids costly end-to-end retraining while maintaining reliable performance with lower training and data costs. Extensive experiments on both user-generated content (UGC) and AI-generated content (AIGC) benchmarks show that DPC-VQA achieves competitive performance against representative baselines, while using less than 2% of the trainable parameters of conventional MLLM-based VQA methods and remaining effective with only 20% of MOS labels. The code will be released upon publication.

23.
arXiv (CS.CV) 2026-06-17

SegTME-UNI2: A Foundation Model-Based Framework for Generalisable Multiclass Cell Segmentation and LLM-Driven Tumour Microenvironment Characterisation in Histopathology

Characterising the tumour microenvironment (TME) from routine H&E-stained histology images requires simultaneous cell segmentation, feature extraction, and interpretable clinical reporting. We present SEGTME-UNI2, a unified framework addressing these requirements. Its core is UNI2-UPERHOVER, a dual-head segmentation model pairing the UNI2-H pathology foundation model (ViT-Giant, pretrained on >100M tiles from 100K slides) with two parallel UperNet decoders: one for six-class semantic segmentation and one for horizontal-vertical gradient regression enabling watershed-based nuclear instance separation. To address the lack of pixel-level annotations in large real-world repositories, UNI2-UPERHOVER undergoes a three-stage progressive pseudo-label curriculum. Each stage trains a fresh model without weight transfer, driving improvement entirely via increased pseudo-label quality: Stage 1: Uses human-annotated PanNuke (7,901 images, 189,744 nuclei, 0.25 um/pixel). Stage 2: Uses entropy-filtered pseudo-labels from the Stage 1 model on 271,711 TCGA-UT scale-0 patches (0.5 um/pixel). Stage 3: Uses pseudo-labels from the Stage 2 model on all 1,608,060 TCGA-UT patches across six resolution scales (0.5-1.0 um/pixel). Segmentation outputs feed a structured TME feature extraction pipeline computing 20+ per-patch compositional, morphological, spatial entropy, and intercellular distance metrics. These are encoded as JSON and passed to a fine-tuned NVIDIA BioNeMo GPT model to generate clinically interpretable TME narratives. Preliminary validation on held-out PanNuke and TCGA-UT partitions demonstrates framework feasibility and internal consistency. The pseudo-labelled TCGA-UT dataset and UNI2-UPERHOVER checkpoint are publicly released to support large-scale TME profiling and spatial biology research.

24.
bioRxiv (Bioinfo) 2026-06-14

TopoMIL: Topology Improves Multiple Instance Learning in Diagnostic Microscopic Images

Microscopic images of cells and tissues are central to disease diagnosis. In computational pathology, multiple instance learning (MIL) has emerged as a key paradigm for analyzing numerous images within a single patient sample. While the representative distribution of cells in a sample is important for diagnosis, existing MIL frameworks largely overlook it. We introduce TopoMIL, a framework that extracts the representative topological structure of the sample and integrates it into the MIL classifier. Three topological representations are assessed, each with distinct advantages and computational costs. We evaluate TopoMIL on four histopathology and cytomorphology datasets, each presenting unique challenges. Integrating the sample's topological information into MIL enhances classification across average, max, attention-based, and transformer pooling, yielding AUCROC gains of 3.3%, 4.2%, 5.9%, and 0.5%, respectively, with moderate computational cost. Our work underscores the potential of TopoMIL as a scalable extension to existing morphology-based models in computational pathology.

25.
bioRxiv (Bioinfo) 2026-06-16

RetroMol: Parsing a shared encoding from natural products and their biosynthetic gene clusters

Natural products such as polyketides and nonribosomal peptides (NRPs) are important sources of bioactive compounds, including many antibiotics. Many of them are assembled by modular enzyme complexes and further modified and diversified by tailoring reactions encoded by biosynthetic gene clusters (BGCs). Although natural products and their coding BGCs describe different data modalities of the same biochemical process, a unified language to jointly describe their biochemistry is lacking. Here we introduce a sequence-based representation of the core biosynthesis of modular natural products, which we call primary sequences, that bridges chemical structures and BGCs. We also present RetroMol, an algorithm that parses either natural product structures or their encoding BGCs into their primary sequences of natural product building blocks. RetroMol allows for similarity scoring between natural products and BGCs, enabling the retrieval of compounds, BGCs, and a combination of the two, based on their biosynthetic similarity. This can, for instance, be used to retrieve biosynthetically similar but structurally dissimilar compounds, or link natural products to candidate coding BGCs in large experimental datasets. We demonstrate the latter by rediscovering the nocardichelin B BGC as a proof of principle. We also exemplify the utility of biosynthetic similarity by showing various pairs of biosynthetically similar compounds with low structural similarity. Together, these results establish primary sequences as a shared biosynthetic encoding for natural product comparison and BGC prioritization.