CP-Agent: Context-Aware Multimodal Reasoning for Cellular Morphological Profiling under Chemical Perturbations

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.

MoleculeNet: A Benchmark for Molecular Machine Learning

Molecular machine learning has been maturing rapidly over the last few years. Improved methods and the presence of larger datasets have enabled machine learning algorithms to make increasingly accurate predictions about molecular properties. However, algorithmic progress has been limited due to the lack of a standard benchmark to compare the efficacy of proposed methods; most new algorithms are benchmarked on different datasets making it challenging to gauge the quality of proposed methods. This work introduces MoleculeNet, a large scale benchmark for molecular machine learning. MoleculeNet curates multiple public datasets, establishes metrics for evaluation, and offers high quality open-source implementations of multiple previously proposed molecular featurization and learning algorithms (released as part of the DeepChem open source library). MoleculeNet benchmarks demonstrate that learnable representations are powerful tools for molecular machine learning and broadly offer the best performance. However, this result comes with caveats. Learnable representations still struggle to deal with complex tasks under data scarcity and highly imbalanced classification. For quantum mechanical and biophysical datasets, the use of physics-aware featurizations can be more important than choice of particular learning algorithm.

PotentialNet for Molecular Property Prediction

The arc of drug discovery entails a multiparameter optimization problem spanning vast length scales. They key parameters range from solubility (angstroms) to protein-ligand binding (nanometers) to in vivo toxicity (meters). Through feature learning---instead of feature engineering---deep neural networks promise to outperform both traditional physics-based and knowledge-based machine learning models for predicting molecular properties pertinent to drug discovery. To this end, we present the PotentialNet family of graph convolutions. These models are specifically designed for and achieve state-of-the-art performance for protein-ligand binding affinity. We further validate these deep neural networks by setting new standards of performance in several ligand-based tasks. In parallel, we introduce a new metric, the Regression Enrichment Factor $EF_\chi^{(R)}$, to measure the early enrichment of computational models for chemical data. Finally, we introduce a cross-validation strategy based on structural homology clustering that can more accurately measure model generalizability, which crucially distinguishes the aims of machine learning for drug discovery from standard machine learning tasks.