A Matrix Variational Auto-Encoder for Variant Effect Prediction in Pharmacogenes

Variant effect predictors (VEPs) aim to assess the functional impact of protein variants, traditionally relying on multiple sequence alignments (MSAs). This approach assumes that naturally occurring variants are fit, an assumption challenged by pharmacogenomics, where some pharmacogenes experience low evolutionary pressure. Deep mutational scanning (DMS) datasets provide an alternative by offering quantitative fitness scores for variants. In this work, we propose a transformer-based matrix variational auto-encoder (matVAE) with a structured prior and evaluate its performance on 33 DMS datasets corresponding to 26 drug target and ADME proteins from the ProteinGym benchmark. Our model trained on MSAs (matVAE-MSA) outperforms the state-of-the-art DeepSequence model in zero-shot prediction on DMS datasets, despite using an order of magnitude fewer parameters and requiring less computation at inference time. We also compare matVAE-MSA to matENC-DMS, a model of similar capacity trained on DMS data, and find that the latter performs better on supervised prediction tasks. Additionally, incorporating AlphaFold-generated structures into our transformer model further improves performance, achieving results comparable to DeepSequence trained on MSAs and finetuned on DMS. These findings highlight the potential of DMS datasets to replace MSAs without significant loss in predictive performance, motivating further development of DMS datasets and exploration of their relationships to enhance variant effect prediction.

A Novel Augmented Reality Ultrasound Framework Using an RGB-D Camera and a 3D-printed Marker

Purpose. Ability to locate and track ultrasound images in the 3D operating space is of great benefit for multiple clinical applications. This is often accomplished by tracking the probe using a precise but expensive optical or electromagnetic tracking system. Our goal is to develop a simple and low cost augmented reality echography framework using a standard RGB-D Camera. Methods. A prototype system consisting of an Occipital Structure Core RGB-D camera, a specifically-designed 3D marker, and a fast point cloud registration algorithm FaVoR was developed and evaluated on an Ultrasonix ultrasound system. The probe was calibrated on a 3D-printed N-wire phantom using the software PLUS toolkit. The proposed calibration method is simplified, requiring no additional markers or sensors attached to the phantom. Also, a visualization software based on OpenGL was developed for the augmented reality application. Results. The calibrated probe was used to augment a real-world video in a simulated needle insertion scenario. The ultrasound images were rendered on the video, and visually-coherent results were observed. We evaluated the end-to-end accuracy of our AR US framework on localizing a cube of 5 cm size. From our two experiments, the target pose localization error ranges from 5.6 to 5.9 mm and from -3.9 to 4.2 degrees. Conclusion. We believe that with the potential democratization of RGB-D cameras integrated in mobile devices and AR glasses in the future, our prototype solution may facilitate the use of 3D freehand ultrasound in clinical routine. Future work should include a more rigorous and thorough evaluation, by comparing the calibration accuracy with those obtained by commercial tracking solutions in both simulated and real medical scenarios.