We propose Adaptive Deep Kernel Fitting with Implicit Function Theorem (ADKF-IFT), a novel framework for learning deep kernel Gaussian processes (GPs) by interpolating between meta-learning and conventional deep kernel learning. Our approach employs a bilevel optimization objective where we meta-learn generally useful feature representations across tasks, in the sense that task-specific GP models estimated on top of such features achieve the lowest possible predictive loss on average. We solve the resulting nested optimization problem using the implicit function theorem (IFT). We show that our ADKF-IFT framework contains previously proposed Deep Kernel Learning (DKL) and Deep Kernel Transfer (DKT) as special cases. Although ADKF-IFT is a completely general method, we argue that it is especially well-suited for drug discovery problems and demonstrate that it significantly outperforms previous state-of-the-art methods on a variety of real-world few-shot molecular property prediction tasks and out-of-domain molecular property prediction and optimization tasks. Many real-world applications require machine learning algorithms to make robust predictions with well-calibrated uncertainty given very limited training data. One important example is drug discovery, where practitioners not only want models to accurately predict biochemical/physicochemical properties of molecules, but also want to use models to guide the search for novel molecules with desirable properties, leveraging techniques such as Bayesian optimization (BO) which heavily rely on accurate uncertainty estimates (Frazier, 2018). Despite the meteoric rise of neural networks over the past decade, their notoriously overconfident and unreliable uncertainty estimates (Szegedy et al., 2013) make them generally ineffective surrogate models for BO. Instead, most contemporary BO implementations use Gaussian processes (GPs) (Rasmussen & Williams, 2006) as surrogate models due to their analytically-tractable and generally reliable uncertainty estimates, even on small datasets. Traditionally, GPs are fit on hand-engineered features (e.g., molecular fingerprints), which can limit their predictive performance on complex, structured, high-dimensional data where designing informative features is challenging (e.g., molecules). Naturally, a number of works have proposed to improve performance by instead fitting GPs on features learned by a deep neural network: a family of models generally called Deep Kernel GPs.

Many important problems in science and engineering, such as drug design, involve optimizing an expensive black-box objective function over a complex, high-dimensional, and structured input space. Although machine learning techniques have shown promise in solving such problems, existing approaches substantially lack sample efficiency. We introduce an improved method for efficient black-box optimization, which performs the optimization in the low-dimensional, continuous latent manifold learned by a deep generative model. In contrast to previous approaches, we actively steer the generative model to maintain a latent manifold that is highly useful for efficiently optimizing the objective. We achieve this by periodically retraining the generative model on the data points queried along the optimization trajectory, as well as weighting those data points according to their objective function value. This weighted retraining can be easily implemented on top of existing methods, and is empirically shown to significantly improve their efficiency and performance on synthetic and real-world optimization problems.