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01.
arXiv (CS.LG) 2026-06-19

Benign overfitting beyond prediction: The ordinary least squares interpolator

arXiv:2309.15769v3 Announce Type: replace-cross Abstract: Recent advances in deep learning have highlighted the phenomenon of benign overfitting in overparameterized statistical models, sparking significant interest in understanding its foundations. Owing to its simplicity and practical relevance, the ordinary least squares (OLS) interpolator has become a key object of study for gaining theoretical insight into this phenomenon. While the properties of OLS are well understood in classical underparameterized settings, its behavior in the overparameterized regime – unlike that of ridge regression or the lasso – remains comparatively less explored. We contribute to this growing literature by deriving new algebraic and statistical results for the minimum $\ell_2$-norm OLS interpolator. In contrast to much of the existing work, which focuses on prediction risk, we center our analysis on parameter estimation and inference, which are fundamental for many statistics and causal inference applications. Specifically, we establish overparameterized analogues of (i) the leave-$k$-out formulas, (ii) the omitted variable bias formula, and (iii) the Frisch-Waugh-Lovell theorem. Under the Gauss-Markov model, we further extend the Gauss-Markov theorem and analyze variance estimation under homoskedasticity in the overparameterized setting. Collectively, these results provide a systematic framework for studying parameter estimation and inference in overparameterized linear models, offering a novel perspective on benign overfitting beyond its implications for prediction.

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

Attention, not scale, drives human-AI alignment in multimodal language prediction

Humans routinely draw on visual context to predict upcoming words. To what extent current vision-language models produce comparable behaviour is unclear. Here we placed five state-of-the-art pretrained systems side-by-side with 600 human participants in a web-based Visual-World Paradigm. On each of 100 six-second movie clips, models and participants received either text only or synchronised video and text and judged how likely a specified target word was to appear next; human eye movements were tracked throughout. Adding visual context increased model-human alignment in predictability ratings across all architectures (average Delta r = 0.18) with no impact of parameter size. When visual context was informative, transformer attention significantly increased alignment. Attention maps from two transformer models corresponded with human gaze, explaining up to 70% of the inter-participant variance when the scene contained informative cues. Notably, cross-modal attention reliably tracked anticipatory human fixations on semantic cues. These results suggest that current transformer-based vision-language models can approximate human behaviour exploiting visual context during language prediction - and that selective attention to informative cues, not sheer model scale, is the principal driver of this alignment.

03.
arXiv (CS.AI) 2026-06-18

DN-Hypo-Pipeline: An AI-Driven Workflow for Hypothesis Generation via Large Language Models and Scientific Explanations

arXiv:2606.08532v2 Announce Type: replace Abstract: A scientific hypothesis is the first step in research and undergoes experimental validation, yet it also reflects a deep understanding of and reasoning about scientific phenomena. We introduce DN-Hypo-Pipeline, an AI-powered workflow based on large language models, designed to support structured scientific thinking and hypothesis generation by leveraging scientific explanations as prior knowledge. This pipeline assists researchers in deriving novel hypotheses from existing literature. Given the explanandum (i.e., the conclusion) of a research paper, it identifies underlying laws, theories, and principles, and reconstructs a new, yet-to-be-verified explanation for the observed phenomenon. We evaluated DN-Hypo-Pipeline in the field of data science modeling using three highly cited papers. Statistical inference, supported by both LLM-as-judge assessment and human expert evaluation, demonstrates that our pipeline is more effective than direct generation methods. Additionally, we validated the two highest-scoring generated hypotheses by developing corresponding novel algorithms, which outperformed the baseline models presented in the original papers. Beyond application in data science, DN-Hypo-Pipeline provides a theoretical framework that not only encompasses theory-guided data science modeling methods but also reveals a more fundamental structure of the modeling process. Moreover, this approach is essentially a generalization of theory-guided modeling, offering potential for extension to other domains and across a broader range of scientific disciplines.

04.
bioRxiv (Bioinfo) 2026-06-11

Machine Learning-Guided Discovery of Bacterial-Selective Membrane-Active Compounds Reveals Mechanistic Bias in Antibiotic Training Datasets

The rise of antibiotic resistance necessitates the discovery of antibacterial compounds with novel mechanisms of action (MoAs). Recent machine learning approaches have shown promise in antibacterial compound discovery, but often identify derivatives of known antibiotic classes rather than mechanistically novel compounds. Previous approaches applied Tanimoto similarity filters at the end of screening pipelines, but this method has substantial drawbacks: Tanimoto similarity can be misleading in chemical space, and post-hoc filtering does not influence what activity models learn to prioritize. Here, we present a machine learning pipeline that addresses chemical novelty upfront by employing an XGBoost-based MoA classifier to explicitly prioritize compounds predicted to have mechanisms distinct from known antibiotic classes, combined with graph neural networks for antibacterial activity and toxicity prediction. Applied to the Zinc20 database, our approach successfully identified non-toxic antibacterial compounds structurally distinct from known antibiotics. Notably, the majority of these hits exhibited membrane-targeting activity with selectivity for bacterial cells over mammalian cells, suggesting potential for next-generation membrane-active antibiotics. However, we did not identify compounds with novel protein targets. Systematic analysis revealed that this limitation stems from mechanistic bias in training data rather than model architecture. Specifically, our activity model learned to preferentially score compounds similar to specific groups in the training data, thus overrepresenting certain MoA classes including membrane-active compounds. Even substantial model architecture and training data enhancements did not overcome this constraint. Our findings demonstrate that the primary bottleneck for discovering mechanistically novel antibiotics is the scarcity of diverse, mechanistically-annotated training data. This work provides both a methodological framework for mechanism-aware screening and critical insights into data requirements for genuinely novel antibiotic discovery.

05.
arXiv (CS.LG) 2026-06-18

Learning to Annotate Delayed and False AEB Events: A Practical System for Extreme Class Imbalance and Asymmetric Label Noise

arXiv:2606.19186v1 Announce Type: cross Abstract: Autonomous Emergency Braking (AEB) optimization relies on accurately annotated real-world trigger events, particularly rare but critical delayed and false AEB triggers that expose system deficiencies. However, these minority samples comprise less than 5% of thousands of daily triggers, making manual annotation prohibitively expensive at scale. We present the first automated AEB annotation framework to address this problem. During development, we identified two fundamental challenges that severely impair delayed/false trigger annotation accuracy: (1) Extreme class imbalance where delayed/false triggers are overwhelmed by true triggers; (2) Asymmetric label noise where mislabeled majority samples (true triggers) suppress minority samples (delayed/false triggers) learning. To overcome these challenges, we propose two key innovations: (1) Specific data augmentation that synthesizes realistic samples by manipulating focal target attributes, transplanting ego-vehicle dynamics, and masking non-focal agents; (2) noise suppression using stable hardness estimation and probe-guided adaptive threshold to clean mislabeled true trigger samples. Crucially, we deploy our model as a practical annotation system with full-stack architecture, efficiently identifying critical delayed/false triggers from thousands of daily AEB events. Production results demonstrate 80% improvement in recall of delayed/false triggers and 50% reduction in manual workload. Beyond immediate gains, the system enables continuous self-improvement through accumulated high-quality annotations, establishing a necessary data foundation for on-vehicle AEB system optimization

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

Limitations of SGD for Multi-Index Models Beyond Statistical Queries

arXiv:2602.05704v2 Announce Type: replace Abstract: Understanding the limitations of gradient methods, and stochastic gradient descent (SGD) in particular, is a central challenge in learning theory. To that end, a commonly used tool is the Statistical Queries (SQ) framework, which studies performance limits of algorithms based on noisy interaction with the data. However, it is known that the formal connection between the SQ framework and SGD is tenuous: Existing results typically rely on adversarial or specially-structured gradient noise that does not reflect the noise in standard SGD, and (as we point out here) can sometimes lead to incorrect predictions. Moreover, many analyses of SGD for challenging problems rely on non-trivial algorithmic modifications, such as restricting the SGD trajectory to the sphere or using very small learning rates. To address these shortcomings, we develop a new, non-SQ framework to study the limitations of standard vanilla SGD, for single-index and multi-index models (namely, when the target function depends on a low-dimensional projection of the inputs). Our results apply to a broad class of settings and architectures, including (potentially deep) neural networks.

07.
arXiv (CS.CV) 2026-06-11

AnchorEdit: Maintaining Temporal Consistency in Multi-turn Image Editing via Causal Memory

Multi-turn image editing is essential for iterative design, yet current models often struggle with identity drift and error accumulation over successive steps. While existing research leverages video priors for consistency, their reliance on bidirectional attention is fundamentally misaligned with the causal, sequential nature of interactive editing. In this paper, we propose AnchorEdit, the first autoregressive (AR) diffusion-based framework designed specifically for high-resolution, long-term multi-turn editing. AnchorEdit bridges the gap between video priors and causal inference through a three-stage training curriculum: identity-preserving sing-turn pretraining, causal AR forcing fine-tuning with a novel self-rollout strategy to mitigate exposure bias, and consistency distillation for efficient 4-step generation. During inference, we introduce a memory mechanism to anchor the initial subject identity and ensure stable extrapolation across extended editing trajectories. To evaluate performance, we provide a new high-resolution multi-turn editing benchmark designed to stress-test long-horizon stability. Extensive experiments demonstrate that AnchorEdit achieves state-of-the-art results, maintaining exceptional subject fidelity and instruction following even over 10+ interaction rounds.

08.
arXiv (CS.LG) 2026-06-15

Lyapunov-Based Sample Complexity Analysis for Weakly-Coupled MDPs

arXiv:2606.14095v1 Announce Type: new Abstract: We study the sample complexity of learning in average-reward weakly-coupled Markov decision processes (WCMDPs) and Restless Bandits (RBs) under a generative model. Naive reduction to a tabular MDP leads to high complexity bounds as the state-action space is exponentially large in the number of arms $N$. By exploiting the weakly coupled structure, we show that near-optimal policies can be learned with sample and computational complexities that are polynomial in $N$. Specifically, we analyze the plug-in approach, which applies an efficient planning algorithm to an empirical model estimated from data. For fully heterogeneous WCMDPs, we establish the first finite-sample PAC guarantee with polynomial complexity and an $O(1/\sqrt{N})$ optimality gap. For homogeneous RBs, we further prove that a smaller optimality gap is achievable under mild structural assumptions. A primary technical contribution of our work is a novel Lyapunov-based analysis framework. Unlike classical approaches that rely on the difficult-to-control bias function, our framework uses an explicitly constructed Lyapunov function along with a drift transfer technique between the true and empirical models. A key step of independent interest in our framework is a fine-grained perturbation analysis for the underlying linear programming (LP) relaxation, which provides a general tool for analyzing LP-based policies and weakly-coupled systems.

09.
arXiv (CS.LG) 2026-06-12

Plan, Don't Pose: Long Composite Motion Generation with Text-Aligned BFM

arXiv:2605.29906v2 Announce Type: replace Abstract: Text-to-motion (T2M) generation has broad applications in character animation, virtual avatars, and human-robot interaction. Existing methods typically generate pose trajectories or motion tokens directly from language, forcing a single model to handle semantic interpretation, long-horizon structure, and low-level physical realization. This coupling makes them costly and often unreliable for long, compositional, or semantically dense prompts. We propose Text2BFM, the first framework that aligns natural language with pretrained Behavioral Foundation Models (BFMs) for T2M generation without relying on heavy end-to-end motion generators. Text2BFM operates in the latent policy space of a frozen BFM, using it as an executable motion prior. A text-aligned variational behavioral bottleneck compresses BFM policy-latent sequences into compact motion representations that are compatible with language and preserve long-horizon behavioral structure. Generation is performed in this compact behavioral manifold with a lightweight conditional generator, and the resulting latent encoded behaviors are decoded into policy latents that drive the pretrained frozen BFM. By decoupling semantic planning from motion execution, Text2BFM achieves efficient, robust T2M generation and strong performance on long, compositional textual descriptions.

10.
arXiv (CS.CV) 2026-06-16

Is My Vision-Language Data in Your AI? Membership Inference Test (MINT) Demo 2

We present the Membership Inference Test (MINT) Demo 2, a framework designed to improve transparency in machine learning training processes. MINT is a technique for experimentally determining whether specific data were used during machine learning model training. We establish the theoretical framework and propose multiple architectures for MINT depending on the amount of information known about the models that are being audited. Experimental results using a popular face recognition model, 4 state-of-the-art LLMs, and multiple, diverse, and large-scale public image and text databases achieve promising accuracy levels in the detection of training data of up to 90%. Building on these results, we introduce a comprehensive web platform1 that expands these capabilities to image and text modalities. The platform integrates a diverse technological stack, including MINT, aMINT, and gMINT, allowing users to audit a wide range of models. This demonstrator aims to promote AI transparency and provides a practical tool to foster compliance with emerging AI regulations.

11.
arXiv (CS.CL) 2026-06-25

Cliff Tokens: Identifying Single-Token Failure Triggers in LLM Mathematical Reasoning

Large language models (LLMs) reach high accuracy in mathematical reasoning, but individual traces on the same problem diverge; some arrive at the correct answer while others fail. Prior work analyzes failure at the step, chunk, or sentence level, or at tokens where failure has already occurred. Neither identifies the precise token that triggers the shift toward failure. We introduce the cliff token, a token where the token-wise potential drops significantly under an adaptive threshold that scales with the local token-wise potential, based on a one-sided two-proportion z-test. Across seven models and three mathematical reasoning benchmarks (GSM1K, MATH500, AIME 2025), cliff tokens act as failure triggers; deleting the first cliff token and resampling recovers pass@64 to 1.0, while keeping it limits recovery to between 0.71 and 1.00. We further introduce a cliff taxonomy of deterministic, uncertain, and sampled-off cliffs, defined by greedy choice and token entropy. Each type has distinct probabilistic characteristics, and the taxonomy generalizes across model scales. Finally, we validate the taxonomy via single-token preference optimization at cliff positions (Cliff-DPO). Trained on GSM8K, Cliff-DPO improves accuracy across benchmarks by up to +6.6. Optimizing at uncertain and sampled-off cliffs improves reasoning, while deterministic cliffs do not.

12.
arXiv (CS.CL) 2026-06-24

Same Lesson, Different Story: Cross-Lingual Reconstruction of Cultural Narratives in Large Language Models

The evaluation of cultural grounding context becomes complex when multiple cultures convey the same moral lesson. This challenge is particularly relevant to large language models (LLMs), which produce narratives across a wide range of languages and cultural contexts. However, it remains uncertain whether these models preserve culturally grounded meaning when equivalent moral lessons are conveyed through distinct cultural forms. This study introduces a multilingual evaluation narrative framework that integrates a cross-linguistic collection of 414 proverbs spanning 15 languages and uses four LLMs to generate 13k narratives. By employing semantically equivalent proverbs as culturally grounded prompts, the analysis assesses whether models preserve meaning across languages, how cross-lingual conditioning influences narrative realization, and whether different model families converge on similar interpretations. Results indicate that cross-lingual prompting largely preserves proverb-level semantic meaning while systematically redistributing agency, social positioning, and narrative structure. Additionally, strong inter-model convergence is observed in both monolingual and cross-lingual settings, suggesting that multilingual LLMs rely on shared semantic abstractions despite architectural and linguistic differences. These findings shed light on the need for more comprehensive evaluations of cultural grounding. Relying exclusively on semantic similarity in multilingual narrative assessments may overestimate cultural preservation by neglecting culturally meaningful variations in narrative expression.

13.
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.

14.
arXiv (CS.CL) 2026-06-18

SciHorizon-GENE: Benchmarking LLM for Life Sciences Inference from Gene Knowledge to Functional Understanding

Large language models (LLMs) have shown growing promise in biomedical research, particularly for knowledge-driven interpretation tasks. However, their ability to reliably reason from gene-level knowledge to functional understanding, a core requirement for knowledge-enhanced cell atlas interpretation, remains largely underexplored. To address this gap, we introduce SciHorizon-GENE, a large-scale gene-centric benchmark constructed from authoritative biological databases. The benchmark integrates curated knowledge for over 190K human genes and comprises more than 540K questions covering diverse gene-to-function reasoning scenarios relevant to cell type annotation, functional interpretation, and mechanism-oriented analysis. Motivated by behavioral patterns observed in preliminary examinations, SciHorizon-GENE evaluates LLMs along four biologically critical perspectives: research attention sensitivity, hallucination tendency, answer completeness, and literature influence, explicitly targeting failure modes that limit the safe adoption of LLMs in biological interpretation pipelines. We systematically evaluate a wide range of state-of-the-art general-purpose and biomedical LLMs, revealing substantial heterogeneity in gene-level reasoning capabilities and persistent challenges in generating faithful, complete, and literature-grounded functional interpretations. Our benchmark establishes a systematic foundation for analyzing LLM behavior at the gene scale and offers insights for model selection and development, with direct relevance to knowledge-enhanced biological interpretation.

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

Direct Fisher Score Estimation for Likelihood Maximization

arXiv:2506.06542v2 Announce Type: replace-cross Abstract: We study the problem of likelihood maximization when the likelihood function is intractable but model simulations are readily available. We propose a sequential, gradient-based optimization method that directly models the Fisher score based on a local score matching technique which uses simulations from a localized region around each parameter iterate. By employing a linear parameterization to the surrogate score model, our technique admits a closed-form, least-squares solution. This approach yields a fast, flexible, and efficient approximation to the Fisher score, effectively smoothing the likelihood objective and mitigating the challenges posed by complex likelihood landscapes. We provide theoretical guarantees for our score estimator, including bounds on the bias introduced by the smoothing. Empirical results on a range of synthetic and real-world problems demonstrate the superior performance of our method compared to existing benchmarks.

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

MiqraBERT: Regression-Based Sentence-BERT Finetuning for Biblical Hebrew Parallel Detection

Textual reuse pervades the Hebrew Bible, yet the computational methods used to detect it still rest largely on lexical overlap, and they falter once a parallel involves paraphrase, lexical substitution, or syntactic reworking. This paper introduces MiqraBERT, a Sentence-BERT model finetuned from AlephBERT (a Modern Hebrew encoder) for verse-level semantic similarity in Biblical Hebrew. The training set comprises 1,650 labeled verse and half-verse pairs: 825 true parallels drawn from the Chronicles synoptic material and from foundational studies of poetic parallelism, balanced against 825 randomly sampled negatives. Through cosine-similarity regression, the model learns an embedding space in which parallel verses cluster together and unrelated verses move apart. We evaluate separation with distribution-based metrics, Wasserstein distance and the overlap coefficient, across ten random seeds. MiqraBERT improves distributional separation 2.7-fold over the pre-trained baseline and reduces the ambiguous overlap region from roughly 24% to about 6%. Narrative synoptic parallels reach a recall@10 of 87.1%; poetic parallels remain difficult, below 9%. This genre-dependent asymmetry confines the model's reliable scope to narrative textual reuse. MiqraBERT is publicly available at https://huggingface.co/davidmsmiley/MiqraBERT

17.
arXiv (CS.LG) 2026-06-15

A Water Efficiency Dataset for African Data Centers

arXiv:2412.03716v3 Announce Type: replace Abstract: Artificial intelligence (AI) computing and data centers consume large amounts of freshwater, both directly for cooling and indirectly for electricity generation. While most attention has been paid to developed countries such as the U.S., this paper presents the first-of-its-kind dataset that combines nation-level weather and electricity generation data to estimate water usage effectiveness for data centers in 41 African countries across five different climate regions. We also use our dataset to evaluate and estimate the water consumption of inference on two large language models (i.e., Llama-3-70B and GPT-4) in 11 selected African countries. Our estimates suggest that writing a 10-page report using Llama-3-70B could consume as much as {0.66 liters} of water, while the water consumption by GPT-4 for the same task may go up to about {59 liters}. For writing a medium-length email of 120-200 words, Llama-3-70B and GPT-4 could consume about {0.13 liters} and {2.9 liters} of water, respectively. All the numbers for generative model inference tasks are based on public information available in 2024, when we initially prepared the analysis. Since then, AI inference systems have improved substantially. For example, recent disclosures suggest that energy efficiency improved by more than 30x between May 2024 and May 2025. Accordingly, our 2024 estimates should be interpreted as historical reference values rather than as representative of current performance. Interestingly, given the same AI model, 9 of the 11 selected African countries consume less water than the global average, mainly because of lower water intensities for electricity generation.

18.
arXiv (CS.AI) 2026-06-11

TAPIOCA: Why Task- Aware Pruning Improves OOD model Capability

arXiv:2605.14738v3 Announce Type: replace-cross Abstract: Recent work has promoted task-aware layer pruning as a way to improve model performance on particular tasks, as shown by TALE. In this paper, we investigate when such improvements occur and why. We show first that, across controlled polynomial regression tasks and large language models, such pruning yields no benefit on in-distribution (ID) data but consistently improves out-of-distribution (OOD) accuracy. We further show empirically that OOD inputs induce layerwise norm and pairwise-distance profiles that deviate from the corresponding ID profiles. This leads to a geometric explanation of task-aware pruning: each task induces a task-adapted geometry, characterized empirically by the representation profiles observed on ID inputs. OOD inputs can introduce a distorted version of the task-adapted geometry. Task-aware pruning identifies layers that create or amplify this distortion; by removing them, it shifts OOD representational norms and pairwise distances toward those observed on the adapted distribution. This realigns OOD inputs with the model's task-adapted geometry and improves performance. We provide causal evidence through controlled distribution shifts and residual-scaling interventions, and demonstrate consistent behavior across model scales.

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

Brep2Shape: Boundary and Shape Representation Alignment via Self-Supervised Transformers

arXiv:2602.07429v2 Announce Type: replace-cross Abstract: Boundary representation (B-rep) is the industry standard for computer-aided design (CAD). While deep learning shows promise in processing B-rep models, existing methods suffer from a representation gap: continuous approaches offer analytical precision but are visually abstract, whereas discrete methods provide intuitive clarity at the expense of geometric precision. To bridge this gap, we introduce Brep2Shape, a novel self-supervised pre-training method designed to align abstract boundary representations with intuitive shape representations. Our method employs a geometry-aware task where the model learns to predict dense spatial points from parametric Bézier control points, enabling the network to better understand physical manifolds derived from abstract coefficients. To enhance this alignment, we propose a Dual Transformer backbone with parallel streams that independently encode surface and curve tokens to capture their distinct geometric properties. Moreover, the topology attention is integrated to model the interdependencies between surfaces and curves, thereby maintaining topological consistency. Experimental results demonstrate that Brep2Shape offers significant scalability, achieving state-of-the-art accuracy and faster convergence across various downstream tasks.Code is available at this repository: https://github.com/thuml/Brep2Shape.

20.
bioRxiv (Bioinfo) 2026-06-13

ADMETron: An AI-driven SaaS platform for comprehensive ADMET prediction and compound prioritisation

ONTOSIGHT(R) ADMETron is an AI-driven platform designed for rapid prediction and visualization of Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties to support modern drug discovery. The platform integrates an interactive web interface with a scalable predictive engine, enabling high-throughput virtual screening and batch analysis of chemical compounds. Its core architecture combines recurrent neural network (RNN)-derived molecular embeddings from SMILES representations with physicochemical descriptors, which are subsequently modeled using gradient boosting machines (GBMs). This framework provides predictions across 34 ADMET endpoints, including physicochemical properties, absorption, CYP450 interactions, hERG liability, and mutagenicity. The predictive performance of ADMETron was evaluated using benchmark datasets from the Therapeutics Data Commons (TDC), demonstrating strong performance and generalizability across both classification and regression tasks. Beyond predictive modeling, the platform introduces an interactive radar graph-based structure-activity relationship (SAR) visualization framework that enables real-time comparison of multiple compounds and reference drugs across selected ADMET parameters. This feature facilitates intuitive interpretation of multidimensional molecular profiles and supports lead optimization and compound prioritization. Comparative assessment against widely used online ADMET tools further demonstrated broad endpoint coverage spanning pharmacokinetic, physicochemical, toxicity, and medicinal chemistry properties within a unified environment. Together, these capabilities establish ADMETron as a comprehensive platform for ADMET assessment and data-driven decision-making in drug discovery. (https://admetron.partex.ai/).

21.
medRxiv (Medicine) 2026-06-17

Performance of five risk stratification tools for paediatric pneumonia against WHO scores using data from the PediCAP trial in sub-Saharan Africa

Background Risk stratification tools for childhood pneumonia have been proposed to improve identification of children at highest risk of death, particularly in low-resource settings. However, their added value over the WHO Integrated Management of Childhood Illness (IMCI) criteria and danger signs remains uncertain. Methods We conducted a secondary analysis of a multi-country randomised controlled trial of children without HIV hospitalised with pneumonia in Mozambique, South Africa, Uganda, Zambia, and Zimbabwe. We evaluated the performance of five published risk scores alongside WHO IMCI severity classification and danger signs. Discrimination for (1) in-hospital mortality, (2) 28-day mortality, and (3) 28-day readmission or death was assessed using area under the receiver operating characteristic curve (AUC). Comparative performance and clinical utility were examined. Results Of the 1010 participants, 18 (1.8%) died in hospital, 22 (2.2%) died in hospital or in the 7 days post-discharge, and 63 (6.2%) died or were readmitted by day 28. Univariate case-fatality rates were highest for variables associated with malnutrition, convulsions, and hypoxaemia. All risk scores demonstrated moderate discrimination for in-hospital and in-hospital+7-day mortality (AUC range approximately 0.75-0.84), with no meaningful differences between models, and performed similarly to the WHO danger signs and IMCI severity classification. In contrast, all approaches performed poorly in predicting 28-day readmission or death (AUC approximately 0.54-0.58). No risk score consistently outperformed simple clinical criteria. Conclusions In this multi-country dataset, we found no evidence that published paediatric pneumonia risk scores meaningfully outperform WHO IMCI-based clinical assessment for predicting mortality. The relatively small number of mortality events limits precision, and modest differences cannot be excluded. These findings suggest that, in low-resource settings, strengthening implementation of existing WHO clinical criteria may be more effective than adopting more complex prediction tools.

22.
arXiv (CS.LG) 2026-06-15

Leave-One-Out-, Bootstrap- and Cross-Conformal Anomaly Detectors

arXiv:2402.16388v4 Announce Type: replace-cross Abstract: The need for uncertainty quantification in anomaly detection systems has become increasingly important. In this context, effectively controlling Type I error rates without inflating Type II error rates in these systems can build trust and reduce costs associated with false discoveries. The field of conformal anomaly detection emerges as a promising approach for providing respective statistical and finite-sample validity guarantees through model calibration. However, reliance on calibration data imposes practical limitations, especially in low-data regimes. In this work, we formally define and evaluate leave-one-out-, bootstrap-, and cross-conformal methods for conformal anomaly detection, building on methods from the field of conformal prediction. Looking beyond the classical split-conformal approach, we show that derived methods for calculating resampling-conformal $p$-values offer a practical compromise between the data efficiency of full-conformal (transductive) approaches and the computational efficiency of split-conformal (inductive) methods. We validate derived methods and quantify their improvements for a range of one-class classifiers and datasets.

23.
bioRxiv (Bioinfo) 2026-06-17

In silico characterization of lysis and host-recognition modules in Staphylococcus aureus bacteriophage genomes

Background/aim: Antimicrobial resistance in methicillin-resistant Staphylococcus aureus (MRSA) requires precision non-antibiotic therapeutics, yet phage lytic efficacy is poorly predicted by phenotypic assays, as shown by paradoxical biofilm responses. This study characterized the genomic architecture of lytic S. aureus bacteriophages, focusing on the conservation of the lysis module and the variability of host-recognition modules, to provide a rational basis for phage candidate selection. Materials and methods: Twenty-two complete S. aureus phage genomes were retrieved from NCBI GenBank. Genomic features were extracted with custom Biopython scripts. Lysis (endolysin, holin) and host-recognition (tail fiber/receptor-binding protein) modules were annotated and validated by InterPro domain analysis, with disrupted endolysins resolved by tBLASTn. Phylogeny was reconstructed from large terminase subunit (TerL) sequences using maximum likelihood. Results: Genome size spanned three classes, from 17.5 to 148.6 kb. The LysK-type endolysin (CHAP, Amidase, SH3b) was highly conserved, whereas tail fiber/RBP genes were detected in only 14 of 22 phages. Domain analysis reclassified two proteins annotated as endolysins as virion-associated peptidoglycan hydrolases, and identified two independent mechanisms, HNH endonuclease insertion and intron splitting, that interrupt lysis-module genes and confound automated annotation. Maximum likelihood analysis recovered a strongly supported, highly conserved core clade with EW and SA13 as divergent lineages. Conclusion: Lysis modules are conserved whereas host-recognition modules are variable, indicating that host recognition rather than the lytic enzyme is the principal determinant of host range and the more rational target for phage selection and engineering.

24.
bioRxiv (Bioinfo) 2026-06-11

STITCH links cellular morphology and gene expression in spatial transcriptomics

In situ spatial (ISS) sequencing can uncover co-variation between cellular morphology and gene expression in vivo. However, a principled and interpretable mathematical representation of morphology has not yet been applied in this context. In particular, current deep learning-based representations of cell images confound a cell's shape with its size. We present an interpretable representation of cellular boundary contours, based on tangent principal component analysis (TPCA) in a Kendall shape manifold, that captures size-independent contour shape features. This approach successfully recovers shape-perturbing genes in an RNAi screen than a previous metric geometry-based approach. We build on TPCA to develop STITCH (Shape-TranscriptomIc Correlation and Harmonization), an approach to reveal covariation between cell morphology with gene expression in ISS datasets. In a Xenium dataset, STITCH outperforms a deep learning-based approach in both recovering the layered organization of keratinocytes and a spatial gradient in nuclear eccentricity. Across samples in a melanoma CosMx dataset, STITCH reproducibly associates elongated and triangular fibroblasts with proximity to malignant cells and myofibroblast-like transcriptional program. Finally, STITCH independently recovers a known link between mesenchymal-like malignant cell states and increased cell area in two melanoma cohorts. STITCH can thus yield interpretable morphology-transcriptome relationships across cell types, patients, and spatial transcriptomics platforms.

25.
bioRxiv (Bioinfo) 2026-06-11

Calibrated Uncertainty Quantification for Patient-Level AML Drug Sensitivity Prediction Using Split Conformal Prediction

Accurate prediction of ex vivo drug sensitivity in acute myeloid leukemia (AML) patients from transcriptomic data is a critical challenge for precision oncology. Existing computational approaches have explored uncertainty quantification in cancer drug response prediction primarily using cell line data, while patient-level AML models typically rely on heuristic confidence measures rather than statistically calibrated uncertainty estimates. Here, we present a framework applying split conformal prediction to patient-level AML drug response modeling using the BeatAML 2.0 cohort. We trained Elastic Net and XGBoost regressors on bulk RNA-seq gene expression profiles from 318 AML patients, analyzing 34,764 patient-drug observations across 122 compounds. Baseline models achieved median Pearson R values of 0.291 (Elastic Net) and 0.281 (XGBoost) across 122 drugs. Wrapping these models with split conformal prediction yielded well-calibrated prediction intervals across three confidence levels: empirical coverages of 81.4%, 90.7%, and 95.5% against nominal targets of 80%, 90%, and 95%, respectively. Analysis of prediction interval widths revealed substantial drug-class-specific uncertainty patterns, with HDAC and BCL-2 inhibitors exhibiting markedly higher uncertainty than MDM2 inhibitors, suggesting a potential association between transcriptomic predictability and drug mechanism of action, although several drug classes were represented by only a small number of compounds. Predictive uncertainty was not significantly associated with ELN2017 molecular risk classification (Kruskal-Wallis p=0.395) or NPM1 mutation status (p=0.788). These results demonstrate that statistically valid uncertainty quantification can be achieved for patient-level AML drug response prediction despite substantial biological heterogeneity. to the best of our knowledge, no published study has applied split conformal prediction to patient-level ex vivo drug sensitivity prediction in the BeatAML cohort, providing a principled alternative to heuristic confidence scoring approaches. Keywords: Acute myeloid leukemia (AML); Ex vivo drug sensitivity; Conformal prediction; Uncertainty quantification; Precision oncology; BeatAML; Transcriptomic biomarkers; Machine learning.