arXiv:2508.04735v2 Announce Type: replace-cross Abstract: Retinal detachment (RD) is a vision-threatening condition that requires prompt intervention to preserve sight. A critical factor in treatment urgency and visual prognosis is macular involvement -- whether the macula is intact or detached. Point-of-care ultrasound (POCUS) is a fast, non-invasive and cost-effective imaging tool commonly used to detect RD in various clinical settings. However, its diagnostic utility is limited by the need for expert interpretation, especially in resource-limited environments. Deep learning has the potential to automate RD detection on ultrasound, but there are no clinically available models, and prior research has not addressed macular status -- an essential distinction for surgical prioritization. Additionally, no public dataset currently supports macular-based RD classification using ultrasound video. We introduce Eye Retinal DEtachment ultraSound (ERDES), the first open-access dataset of ocular ultrasound clips labeled for (i) presence of RD and (ii) macula-detached vs. macula-intact status. ERDES enables machine learning development for RD detection. We also provide baseline benchmarks by training 40 models across eight architectures, including 3D convolutional networks and transformer-based models.

arXiv:2603.02274v1 Announce Type: cross Abstract: Precision oncology is currently limited by the small-N, large-P paradox, where high-dimensional genomic data is abundant, but high-quality drug response samples are often sparse. While deep learning models achieve high predictive accuracy, they remain black boxes that fail to provide the causal mechanisms required for clinical decision-making. We present a Neuro-Symbolic Agentic Framework that bridges this gap by integrating a quantitative machine learning World Model with an LLM-based agentic reasoning layer. Our system utilises a forensic data pipeline built on the Sanger GDSC dataset (N=83), achieving a robust predictive correlation (r=0.504) and a significant performance gain through the explicit modelling of clinical context, specifically Microsatellite Instability (MSI) status. We introduce the concept of Inverse Reasoning, where the agentic layer performs in silico CRISPR perturbations to predict how specific genomic edits, such as APC or TP53 repair, alter drug sensitivity. By distinguishing between therapeutic opportunity and contextual resistance, and validating these findings against human clinical data (p=0.023), our framework provides a transparent, biologically grounded path towards explainable AI in cancer research.

arXiv:2602.18472v1 Announce Type: cross Abstract: Physiologically Based Pharmacokinetic (PBPK) modeling is a cornerstone of model-informed drug development (MIDD), providing a mechanistic framework to predict drug absorption, distribution, metabolism, and excretion (ADME). Despite its utility, adoption is hindered by high computational costs for large-scale simulations, difficulty in parameter identification for complex biological systems, and uncertainty in interspecies extrapolation. In this work, we propose a unified Scientific Machine Learning (SciML) framework that bridges mechanistic rigor and data-driven flexibility. We introduce three contributions: (1) Foundation PBPK Transformers, which treat pharmacokinetic forecasting as a sequence modeling task; (2) Physiologically Constrained Diffusion Models (PCDM), a generative approach that uses a physics-informed loss to synthesize biologically compliant virtual patient populations; and (3) Neural Allometry, a hybrid architecture combining Graph Neural Networks (GNNs) with Neural ODEs to learn continuous cross-species scaling laws. Experiments on synthetic datasets show that the framework reduces physiological violation rates from 2.00% to 0.50% under constraints while offering a path to faster simulation.

arXiv:2602.18915v1 Announce Type: cross Abstract: Adeno-associated viruses (AAVs) are promising vectors for gene therapy, but their native serotypes face limitations in tissue tropism, immune evasion, and production efficiency. Engineering capsids to overcome these hurdles is challenging due to the vast sequence space and the difficulty of simultaneously optimizing multiple functional properties. The complexity also adds when it comes to the kidney, which presents unique anatomical barriers and cellular targets that require precise and efficient vector engineering. Here, we present AAVGen, a generative artificial intelligence framework for de novo design of AAV capsids with enhanced multi-trait profiles. AAVGen integrates a protein language model (PLM) with supervised fine-tuning (SFT) and a reinforcement learning technique termed Group Sequence Policy Optimization (GSPO). The model is guided by a composite reward signal derived from three ESM-2-based regression predictors, each trained to predict a key property: production fitness, kidney tropism, and thermostability. Our results demonstrate that AAVGen produces a diverse library of novel VP1 protein sequences. In silico validations revealed that the majority of the generated variants have superior performance across all three employed indices, indicating successful multi-objective optimization. Furthermore, structural analysis via AlphaFold3 confirms that the generated sequences preserve the canonical capsid folding despite sequence diversification. AAVGen establishes a foundation for data-driven viral vector engineering, accelerating the development of next-generation AAV vectors with tailored functional characteristics.

arXiv:2602.13419v1 Announce Type: cross Abstract: Large Language Models (LLMs) have shown remarkable potential in scientific domains like retrosynthesis; yet, they often lack the fine-grained control necessary to navigate complex problem spaces without error. A critical challenge is directing an LLM to avoid specific, chemically sensitive sites on a molecule - a task where unconstrained generation can lead to invalid or undesirable synthetic pathways. In this work, we introduce Protect$^*$, a neuro-symbolic framework that grounds the generative capabilities of Large Language Models (LLMs) in rigorous chemical logic. Our approach combines automated rule-based reasoning - using a comprehensive database of 55+ SMARTS patterns and 40+ characterized protecting groups - with the generative intuition of neural models. The system operates via a hybrid architecture: an ``automatic mode'' where symbolic logic deterministically identifies and guards reactive sites, and a ``human-in-the-loop mode'' that integrates expert strategic constraints. Through ``active state tracking,'' we inject hard symbolic constraints into the neural inference process via a dedicated protection state linked to canonical atom maps. We demonstrate this neuro-symbolic approach through case studies on complex natural products, including the discovery of a novel synthetic pathway for Erythromycin B, showing that grounding neural generation in symbolic logic enables reliable, expert-level autonomy.

arXiv:2507.04704v2 Announce Type: replace-cross Abstract: Understanding how cellular morphology, gene expression, and spatial context jointly shape tissue function is a central challenge in biology. Image-based spatial transcriptomics technologies now provide high-resolution measurements of cell images and gene expression profiles, but existing methods typically analyze these modalities in isolation or at limited resolution. We address the problem by introducing SPATIA, a multi-level generative and predictive model that learns unified, spatially aware representations by fusing morphology, gene expression, and spatial context from the cell to the tissue level. SPATIA also incorporates a novel spatially conditioned generative framework for predicting cell morphologies under perturbations. Specifically, we propose a confidence-aware flow matching objective that reweights weak optimal-transport pairs based on uncertainty. We further apply morphology-profile alignment to encourage biologically meaningful image generation, enabling the modeling of microenvironment-dependent phenotypic transitions. We assembled a multi-scale dataset consisting of 25.9 million cell-gene pairs across 17 tissues. We benchmark SPATIA against 18 models across 12 tasks, spanning categories such as phenotype generation, annotation, clustering, gene imputation, and cross-modal prediction. SPATIA achieves improved performance over state-of-the-art models, improving generative fidelity by 8% and predictive accuracy by up to 3%.

arXiv:2508.01055v4 Announce Type: replace-cross Abstract: Large language models (LLMs) have gained significant attention in chemistry. However, most existing datasets center on molecular-level property prediction and overlook the role of fine-grained functional group (FG) information. Incorporating FG-level data can provide valuable prior knowledge that links molecular structures with textual descriptions, which can be used to build more interpretable, structure-aware LLMs for reasoning on molecule-related tasks. Moreover, LLMs can learn from such fine-grained information to uncover hidden relationships between specific functional groups and molecular properties, thereby advancing molecular design and drug discovery. Here, we introduce FGBench, a dataset comprising 625K molecular property reasoning problems with functional group information. Functional groups are precisely annotated and localized within the molecule, which ensures the dataset's interoperability thereby facilitating further multimodal applications. FGBench includes both regression and classification tasks on 245 different functional groups across three categories for molecular property reasoning: (1) single functional group impacts, (2) multiple functional group interactions, and (3) direct molecular comparisons. In the benchmark of state-of-the-art LLMs on 7K curated data, the results indicate that current LLMs struggle with FG-level property reasoning, highlighting the need to enhance reasoning capabilities in LLMs for chemistry tasks. We anticipate that the methodology employed in FGBench to construct datasets with functional group-level information will serve as a foundational framework for generating new question-answer pairs, enabling LLMs to better understand fine-grained molecular structure-property relationships. The dataset and evaluation code are available at https://github.com/xuanliugit/FGBench.