Matteo Rossi

Miles Wang-Henderson, Benjamin Kaufman, Edward Williams et al.

Batched synthesis and testing of molecular designs is the key bottleneck of drug development. There has been great interest in leveraging biomolecular foundation models as surrogates to accelerate this process. In this work, we show how to obtain scalable probabilistic surrogates of binding affinity for use in Batch Bayesian Optimization (Batch BO). This demands parallel acquisition functions that hedge between designs and the ability to rapidly sample from a joint predictive density to approximate them. Through the framework of Epistemic Neural Networks (ENNs), we obtain scalable joint predictive distributions of binding affinity on top of representations taken from large structure-informed models. Key to this work is an investigation into the importance of prior networks in ENNs and how to pretrain them on synthetic data to improve downstream performance in Batch BO. Their utility is demonstrated by rediscovering known potent EGFR inhibitors on a semi-synthetic benchmark in up to 5x fewer iterations, as well as potent inhibitors from a real-world small-molecule library in up to 10x fewer iterations, offering a promising solution for large-scale drug discovery applications.

Luca Marsilio, Davide Marzorati, Matteo Rossi et al.

Osteoarthritis is a degenerative condition affecting bones and cartilage, often leading to osteophyte formation, bone density loss, and joint space narrowing. Treatment options to restore normal joint function vary depending on the severity of the condition. This work introduces an innovative deep-learning framework processing shoulder CT scans. It features the semantic segmentation of the proximal humerus and scapula, the 3D reconstruction of bone surfaces, the identification of the glenohumeral (GH) joint region, and the staging of three common osteoarthritic-related pathologies: osteophyte formation (OS), GH space reduction (JS), and humeroscapular alignment (HSA). The pipeline comprises two cascaded CNN architectures: 3D CEL-UNet for segmentation and 3D Arthro-Net for threefold classification. A retrospective dataset of 571 CT scans featuring patients with various degrees of GH osteoarthritic-related pathologies was used to train, validate, and test the pipeline. Root mean squared error and Hausdorff distance median values for 3D reconstruction were 0.22mm and 1.48mm for the humerus and 0.24mm and 1.48mm for the scapula, outperforming state-of-the-art architectures and making it potentially suitable for a PSI-based shoulder arthroplasty preoperative plan context. The classification accuracy for OS, JS, and HSA consistently reached around 90% across all three categories. The computational time for the inference pipeline was less than 15s, showcasing the framework's efficiency and compatibility with orthopedic radiology practice. The outcomes represent a promising advancement toward the medical translation of artificial intelligence tools. This progress aims to streamline the preoperative planning pipeline delivering high-quality bone surfaces and supporting surgeons in selecting the most suitable surgical approach according to the unique patient joint conditions.