Ping Shu Ho

Yuxin Zhang, Yiyao Li, Ping Shu Ho et al.

Cell Painting combines multiplexed fluorescent staining, high-content imaging, and quantitative analysis to generate high-dimensional phenotypic readouts to support diverse downstream tasks such as mechanism-of-action (MoA) inference, toxicity prediction, and construction of drug-disease atlases. However, existing workflows are slow, costly and difficult to interpret. Approaches for drug screening modeling predominantly focus on molecular representation learning, while neglecting actual experimental context (e.g., cell line, dosing schedule, etc.), limiting generalization and MoA resolution. We introduce CP-Agent, an agentic multimodal large language model (MLLM) capable of generating mechanism-relevant, human-interpretable rationales for cell morphological changes under drug perturbations. At its core, CP-Agent leverages a context-aware alignment module, CP-CLIP, that jointly embeds high-content images and experimental metadata to enable robust treatment and MoA discrimination (achieving a maximum F1-score of 0.896). By integrating CP-CLIP outputs with agentic tool usage and reasoning, CP-Agent compiles rationales into a structured report to guide experimental design and hypothesis refinement. These capabilities highlight CP-Agent's potential to accelerate drug discovery by enabling more interpretable, scalable, and context-aware phenotypic screening -- streamlining iterative cycles of hypothesis generation in drug discovery.

Minkyung Cha, Jooyoung Bae, Jaewon Jung et al.

Functional Magnetic Resonance Imaging(fMRI) has now become a classic way for measuring brain activity, and recent trend is shifting toward utilizing fMRI brain data for AI-driven diagnosis. Given that the brain functions as not a discrete but interconnected whole, Graph-based architectures represented by Graph Convolutional Network(GCN) has emerged as a dominant framework for such task, since they are capable of treating ROIs as dynamically interconnected nodes and extracting relational architecture between them. Ironically, however, it is the very nature of GCN's architecture that acts as an obstacle to its performance. The mathematical foundation of GCN, effective for capturing global regularities, acts as a tradeoff; by smoothing features across the connected nodes repeatedly, traditional GCN tend to blur out the contrastive dynamics that might be crucial in identifying certain neurological disorders. In order to break through this structural bottleneck, we propose LUMINA, a Laplacian-Unifying Mechanism for Interpretable Neurodevelopmental Analysis. Our model is a Quad-Stream GCN that employs a bipolar RELU activation and a dual-spectrum graph Laplacian filtering mechanism, thereby capturing heterogeneous dynamics that were often blurred out in conventional GCN. By doing so, we can preserve the diverse range and characteristics of neural connections in each fMRI data. Through 5-fold cross validation on the ADHD200(N=144) and ABIDE(N=579) dataset, LUMINA demonstrates stable diagnostic performance in two of the most critical neurodevelopmental disorder in childhood, ADHD and ASD, outperforming existing models with an accuracy of 84.66% and 88.41% each.

Gavin Wong, Ping Shu Ho, Ivan Au Yeung et al.

Biological pathways map gene-gene interactions that govern all human processes. Despite their importance, most ML models treat genes as unstructured tokens, discarding known pathway structure. The latest pathway-informed models capture pathway-pathway interactions, but still treat each pathway as a "bag of genes" via MLPs, discarding its topology and gene-gene interactions. We propose a Graph Attention Network (GAT) framework that models pathways at the gene level. We show that GATs generalize much better than MLPs, achieving an 81% reduction in MSE when predicting pathway dynamics under unseen treatment conditions. We further validate the correctness of our biological prior by encoding drug mechanisms via edge interventions, boosting model robustness. Finally, we show that our GAT model is able to correctly rediscover all five gene-gene interactions in the canonical TP53-MDM2-MDM4 feedback loop from raw time-series mRNA data, demonstrating potential to generate novel biological hypotheses directly from experimental data.