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Over the last decade, there has been significant progress in the field of machine learning for de novo drug design, particularly in deep generative models. However, current generative approaches exhibit a significant challenge as they do not ensure that the proposed molecular structures can be feasibly synthesized nor do they provide the synthesis routes of the proposed small molecules, thereby seriously limiting their practical applicability. In this work, we propose a novel forward synthesis framework powered by reinforcement learning (RL) for de novo drug design, Policy Gradient for Forward Synthesis (PGFS), that addresses this challenge by embedding the concept of synthetic accessibility directly into the de novo drug design system. In this setup, the agent learns to navigate through the immense synthetically accessible chemical space by subjecting commercially available small molecule building blocks to valid chemical reactions at every time step of the iterative virtual multi-step synthesis process. The proposed environment for drug discovery provides a highly challenging test-bed for RL algorithms owing to the large state space and high-dimensional continuous action space with hierarchical actions. PGFS achieves state-of-the-art performance in generating structures with high QED and penalized clogP. Moreover, we validate PGFS in an in-silico proof-of-concept associated with three HIV targets. Finally, we describe how the end-to-end training conceptualized in this study represents an important paradigm in radically expanding the synthesizable chemical space and automating the drug discovery process., Comment: added the statistics of top-100 compounds used logP metric with scaled components added values of the initial reactants to the box plots some values in tables are recalculated due to the inconsistent environments on different machines. corresponding benchmarks were rerun with the requirements on github. no significant changes in the results. corrected figures in the Appendix

We present a novel graph-neural-network-based system to effectively represent large-scale 3D point clouds with the applications to autonomous driving. Many previous works studied the representations of 3D point clouds based on two approaches, voxelization, which causes discretization errors and learning, which is hard to capture huge variations in large-scale scenarios. In this work, we combine voxelization and learning: we discretize the 3D space into voxels and propose novel graph inception networks to represent 3D points in each voxel. This combination makes the system avoid discretization errors and work for large-scale scenarios. The entire system for large-scale 3D point clouds acts like the blocked discrete cosine transform for 2D images; we thus call it the point cloud neural transform (PCT). We further apply the proposed PCT to represent real-time LiDAR sweeps produced by self-driving cars and the PCT with graph inception networks significantly outperforms its competitors.

In this paper, we introduce a generalized value iteration network (GVIN), which is an end-to-end neural network planning module. GVIN emulates the value iteration algorithm by using a novel graph convolution operator, which enables GVIN to learn and plan on irregular spatial graphs. We propose three novel differentiable kernels as graph convolution operators and show that the embedding based kernel achieves the best performance. We further propose episodic Q-learning, an improvement upon traditional n-step Q-learning that stabilizes training for networks that contain a planning module. Lastly, we evaluate GVIN on planning problems in 2D mazes, irregular graphs, and real-world street networks, showing that GVIN generalizes well for both arbitrary graphs and unseen graphs of larger scale and outperforms a naive generalization of VIN (discretizing a spatial graph into a 2D image)., Comment: 14 pages, conference

What is the best way to describe a user in a social network with just a few numbers? Mathematically, this is equivalent to assigning a vector representation to each node in a graph, a process called graph embedding. We propose a novel framework, GEM-D that unifies most of the past algorithms such as LapEigs, DeepWalk and node2vec. GEM-D achieves its goal by decomposing any graph embedding algorithm into three building blocks: node proximity function, warping function and loss function. Based on thorough analysis of GEM-D, we propose a novel algorithm, called UltimateWalk, which outperforms the most-recently proposed state-of-the-art DeepWalk and node2vec. The contributions of this work are: (1) The proposed framework, GEM-D unifies the past graph embedding algorithms and provides a general recipe of how to design a graph embedding; (2) the nonlinearlity in the warping function contributes significantly to the quality of embedding and the exponential function is empirically optimal; (3) the proposed algorithm, UltimateWalk is one-click (no user-defined parameters), scalable and has a closed-form solution.