Kevin McCloskey

Joe Yue-Hei Ng, Kevin McCloskey, Jian Cui et al. · deepmind

Contrails (condensation trails) are line-shaped ice clouds caused by aircraft and are likely the largest contributor of aviation-induced climate change. Contrail avoidance is potentially an inexpensive way to significantly reduce the climate impact of aviation. An automated contrail detection system is an essential tool to develop and evaluate contrail avoidance systems. In this paper, we present a human-labeled dataset named OpenContrails to train and evaluate contrail detection models based on GOES-16 Advanced Baseline Imager (ABI) data. We propose and evaluate a contrail detection model that incorporates temporal context for improved detection accuracy. The human labeled dataset and the contrail detection outputs are publicly available on Google Cloud Storage at gs://goes_contrails_dataset.

Gowoon Cheon, Lusann Yang, Kevin McCloskey et al.

Crystal structure search is a long-standing challenge in materials design. We present a dataset of more than 100,000 structural relaxations of potential battery anode materials from randomized structures using density functional theory calculations. We illustrate the usage of the dataset by training graph neural networks to predict structural relaxations from randomly generated structures. Our models directly predict stresses in addition to forces, which allows them to accurately simulate relaxations of both ionic positions and lattice vectors. We show that models trained on the molecular dynamics simulations fail to simulate relaxations from random structures, while training on our data leads to up to two orders of magnitude decrease in error for the same task. Our model is able to find an experimentally verified structure of a stoichiometry held out from training. We find that randomly perturbing atomic positions during training improves both the accuracy and out of domain generalization of the models.

Kevin McCloskey, Eric A. Sigel, Steven Kearnes et al.

DNA-encoded small molecule libraries (DELs) have enabled discovery of novel inhibitors for many distinct protein targets of therapeutic value through screening of libraries with up to billions of unique small molecules. We demonstrate a new approach applying machine learning to DEL selection data by identifying active molecules from a large commercial collection and a virtual library of easily synthesizable compounds. We train models using only DEL selection data and apply automated or automatable filters with chemist review restricted to the removal of molecules with potential for instability or reactivity. We validate this approach with a large prospective study (nearly 2000 compounds tested) across three diverse protein targets: sEH (a hydrolase), ERα (a nuclear receptor), and c-KIT (a kinase). The approach is effective, with an overall hit rate of {\sim}30% at 30 {\textmu}M and discovery of potent compounds (IC50 <10 nM) for every target. The model makes useful predictions even for molecules dissimilar to the original DEL and the compounds identified are diverse, predominantly drug-like, and different from known ligands. Collectively, the quality and quantity of DEL selection data; the power of modern machine learning methods; and access to large, inexpensive, commercially-available libraries creates a powerful new approach for hit finding.

Kevin McCloskey, Ankur Taly, Federico Monti et al.

Deep neural networks have achieved state of the art accuracy at classifying molecules with respect to whether they bind to specific protein targets. A key breakthrough would occur if these models could reveal the fragment pharmacophores that are causally involved in binding. Extracting chemical details of binding from the networks could potentially lead to scientific discoveries about the mechanisms of drug actions. But doing so requires shining light into the black box that is the trained neural network model, a task that has proved difficult across many domains. Here we show how the binding mechanism learned by deep neural network models can be interrogated, using a recently described attribution method. We first work with carefully constructed synthetic datasets, in which the 'fragment logic' of binding is fully known. We find that networks that achieve perfect accuracy on held out test datasets still learn spurious correlations due to biases in the datasets, and we are able to exploit this non-robustness to construct adversarial examples that fool the model. The dataset bias makes these models unreliable for accurately revealing information about the mechanisms of protein-ligand binding. In light of our findings, we prescribe a test that checks for dataset bias given a hypothesis. If the test fails, it indicates that either the model must be simplified or regularized and/or that the training dataset requires augmentation.

Steven Kearnes, Kevin McCloskey, Marc Berndl et al.

Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular "graph convolutions", a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph---atoms, bonds, distances, etc.---which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement.