Yijie Wang

Junhua Xi, Yifei Shi, Yijie Wang et al.

Learning-based multi-view stereo (MVS) has by far centered around 3D convolution on cost volumes. Due to the high computation and memory consumption of 3D CNN, the resolution of output depth is often considerably limited. Different from most existing works dedicated to adaptive refinement of cost volumes, we opt to directly optimize the depth value along each camera ray, mimicking the range (depth) finding of a laser scanner. This reduces the MVS problem to ray-based depth optimization which is much more light-weight than full cost volume optimization. In particular, we propose RayMVSNet which learns sequential prediction of a 1D implicit field along each camera ray with the zero-crossing point indicating scene depth. This sequential modeling, conducted based on transformer features, essentially learns the epipolar line search in traditional multi-view stereo. We also devise a multi-task learning for better optimization convergence and depth accuracy. Our method ranks top on both the DTU and the Tanks \& Temples datasets over all previous learning-based methods, achieving overall reconstruction score of 0.33mm on DTU and f-score of 59.48% on Tanks & Temples.

Yang Wang, Zanyu Shi, Timothy Richardson et al.

Explainable Graph Neural Networks (GNNs) have been developed and applied to drug-protein binding prediction to identify the key chemical structures in a drug that have active interactions with the target proteins. However, the key structures identified by the current explainable GNN models are typically chemically invalid. Furthermore, a threshold needs to be manually selected to pinpoint the key structures from the rest. To overcome the limitations of the current explainable GNN models, we propose our SLGNN, which stands for using Sparse Learning to Graph Neural Networks. Our SLGNN relies on using a chemical-substructure-based graph (where nodes are chemical substructures) to represent a drug molecule. Furthermore, SLGNN incorporates generalized fussed lasso with message-passing algorithms to identify connected subgraphs that are critical for the drug-protein binding prediction. Due to the use of the chemical-substructure-based graph, it is guaranteed that any subgraphs in a drug identified by our SLGNN are chemically valid structures. These structures can be further interpreted as the key chemical structures for the drug to bind to the target protein. We demonstrate the explanatory power of our SLGNN by first showing all the key structures identified by our SLGNN are chemically valid. In addition, we illustrate that the key structures identified by our SLGNN have more predictive power than the key structures identified by the competing methods. At last, we use known drug-protein binding data to show the key structures identified by our SLGNN contain most of the binding sites.

Zanyu Shi, Yang Wang, Pathum Weerawarna et al.

Explainable artificial intelligence (XAI) approaches have been increasingly applied in drug discovery to learn molecular representations and identify substructures driving property predictions. However, building end-to-end explainable models for structure-activity relationship (SAR) modeling for compound property prediction faces many challenges, such as the limited number of compound-protein interaction activity data for specific protein targets, and plenty of subtle changes in molecular configuration sites significantly affecting molecular properties. We exploit pairs of molecules with activity cliffs that share scaffolds but differ at substituent sites, characterized by large potency differences for specific protein targets. We propose a framework by implementing graph neural networks (GNNs) to leverage property and structure information from activity cliff pairs to predict compound-protein affinity (i.e., half maximal inhibitory concentration, IC50). To enhance model performance and explainability, we train GNNs with structure-aware loss functions using group lasso and sparse group lasso regularizations, which prune and highlight molecular subgraphs relevant to activity differences. We applied this framework to activity cliff data of molecules targeting three proto-oncogene tyrosine-protein kinase Src proteins (PDB IDs: 1O42, 2H8H, 4MXO). Our approach improved property prediction by integrating common and uncommon node information with sparse group lasso, as reflected in reduced root mean squared error (RMSE) and improved Pearson's correlation coefficient (PCC). Applying regularizations also enhances feature attribution for GNN by boosting graph-level global direction scores and improving atom-level coloring accuracy. These advances strengthen model interpretability in drug discovery pipelines, particularly for identifying critical molecular substructures in lead optimization.