Generating molecular graphs with desired chemical properties driven by deep graph generative models provides a very promising way to accelerate drug discovery process. Such graph generative models usually consist of two steps: learning latent representations and generation of molecular graphs. However, to generate novel and chemically-valid molecular graphs from latent representations is very challenging because of the chemical constraints and combinatorial complexity of molecular graphs. In this paper, we propose MoFlow, a flow-based graph generative model to learn invertible mappings between molecular graphs and their latent representations. To generate molecular graphs, our MoFlow first generates bonds (edges) through a Glow based model, then generates atoms (nodes) given bonds by a novel graph conditional flow, and finally assembles them into a chemically valid molecular graph with a posthoc validity correction. Our MoFlow has merits including exact and tractable likelihood training, efficient one-pass embedding and generation, chemical validity guarantees, 100\% reconstruction of training data, and good generalization ability. We validate our model by four tasks: molecular graph generation and reconstruction, visualization of the continuous latent space, property optimization, and constrained property optimization. Our MoFlow achieves state-of-the-art performance, which implies its potential efficiency and effectiveness to explore large chemical space for drug discovery.

The recent success of high-dimensional models, such as deep neural networks (DNNs), has led many to question the validity of the bias-variance tradeoff principle in high dimensions. We reexamine it with respect to two key choices: the model class and the complexity measure. We argue that failing to suitably specify either one can falsely suggest that the tradeoff does not hold. This observation motivates us to seek a valid complexity measure, defined with respect to a reasonably good class of models. Building on Rissanen's principle of minimum description length (MDL), we propose a novel MDL-based complexity (MDL-COMP). We focus on the context of linear models, which have been recently used as a stylized tractable approximation to DNNs in high-dimensions. MDL-COMP is defined via an optimality criterion over the encodings induced by a good Ridge estimator class. We derive closed-form expressions for MDL-COMP and show that for a dataset with $n$ observations and $d$ parameters it is \emph{not always} equal to $d/n$, and is a function of the singular values of the design matrix and the signal-to-noise ratio. For random Gaussian design, we find that while MDL-COMP scales linearly with $d$ in low-dimensions ($dn$) the scaling is exponentially smaller, scaling as $\log d$. We hope that such a slow growth of complexity in high-dimensions can help shed light on the good generalization performance of several well-tuned high-dimensional models. Moreover, via an array of simulations and real-data experiments, we show that a data-driven Prac-MDL-COMP can inform hyper-parameter tuning for ridge regression in limited data settings, sometimes improving upon cross-validation.

Sample-based planning is a powerful family of algorithms for generating intelligent behavior from a model of the environment. Generating good candidate actions is critical to the success of sample-based planners, particularly in continuous or large action spaces. Typically, candidate action generation exhausts the action space, uses domain knowledge, or more recently, involves learning a stochastic policy to provide such search guidance. In this paper we explore explicitly learning a candidate action generator by optimizing a novel objective, marginal utility. The marginal utility of an action generator measures the increase in value of an action over previously generated actions. We validate our approach in both curling, a challenging stochastic domain with continuous state and action spaces, and a location game with a discrete but large action space. We show that a generator trained with the marginal utility objective outperforms hand-coded schemes built on substantial domain knowledge, trained stochastic policies, and other natural objectives for generating actions for sampled-based planners.

Computers have been used to analyze and create music since they were first introduced in the 1950s and 1960s. Beginning in the late 1990s, the rise of the Internet and large scale platforms for music recommendation and retrieval have made music an increasingly prevalent domain of machine learning and artificial intelligence research. While still nascent, several different approaches have been employed to tackle what may broadly be referred to as "musical intelligence." This article provides a definition of musical intelligence, introduces a taxonomy of its constituent components, and surveys the wide range of AI methods that can be, and have been, brought to bear in its pursuit, with a particular emphasis on machine learning methods.

One of the critical challenges in machine learning applications is to have fair predictions. There are numerous recent examples in various domains that convincingly show that algorithms trained with biased datasets can easily lead to erroneous or discriminatory conclusions. This is even more crucial in clinical applications where the predictive algorithms are designed mainly based on a limited or given set of medical images and demographic variables such as age, sex and race are not taken into account. In this work, we conduct a survey of the MICCAI 2018 proceedings to investigate the common practice in medical image analysis applications. Surprisingly, we found that papers focusing on diagnosis rarely describe the demographics of the datasets used, and the diagnosis is purely based on images. In order to highlight the importance of considering the demographics in diagnosis tasks, we used a publicly available dataset of skin lesions. We then demonstrate that a classifier with an overall area under the curve (AUC) of 0.83 has variable performance between 0.76 and 0.91 on subgroups based on age and sex, even though the training set was relatively balanced. Moreover, we show that it is possible to learn unbiased features by explicitly using demographic variables in an adversarial training setup, which leads to balanced scores per subgroups. Finally, we discuss the implications of these results and provide recommendations for further research.

Robust representation learning of temporal dynamic interactions is an important problem in robotic learning in general and automated unsupervised learning in particular. Temporal dynamic interactions can be described by (multiple) geometric trajectories in a suitable space over which unsupervised learning techniques may be applied to extract useful features from raw and high-dimensional data measurements. Taking a geometric approach to robust representation learning for temporal dynamic interactions, it is necessary to develop suitable metrics and a systematic methodology for comparison and for assessing the stability of an unsupervised learning method with respect to its tuning parameters. Such metrics must account for the (geometric) constraints in the physical world as well as the uncertainty associated with the learned patterns. In this paper we introduce a model-free metric based on the Procrustes distance for robust representation learning of interactions, and an optimal transport based distance metric for comparing between distributions of interaction primitives. These distance metrics can serve as an objective for assessing the stability of an interaction learning algorithm. They are also used for comparing the outcomes produced by different algorithms. Moreover, they may also be adopted as an objective function to obtain clusters and representative interaction primitives. These concepts and techniques will be introduced, along with mathematical properties, while their usefulness will be demonstrated in unsupervised learning of vehicle-to-vechicle interactions extracted from the Safety Pilot database, the world's largest database for connected vehicles.

Deep Generative Networks (DGNs) with probabilistic modeling of their output and latent space are currently trained via Variational Autoencoders (VAEs). In the absence of a known analytical form for the posterior and likelihood expectation, VAEs resort to approximations, including (Amortized) Variational Inference (AVI) and Monte-Carlo (MC) sampling. We exploit the Continuous Piecewise Affine (CPA) property of modern DGNs to derive their posterior and marginal distributions as well as the latter's first moments. These findings enable us to derive an analytical Expectation-Maximization (EM) algorithm that enables gradient-free DGN learning. We demonstrate empirically that EM training of DGNs produces greater likelihood than VAE training. Our findings will guide the design of new VAE AVI that better approximate the true posterior and open avenues to apply standard statistical tools for model comparison, anomaly detection, and missing data imputation.

Min-max optimization captures many important machine learning problems such as robust adversarial learning and inverse reinforcement learning, and nonconvex-strongly-concave min-max optimization has been an active line of research. Specifically, a novel variance reduction algorithm SREDA was proposed recently by (Luo et al. 2020) to solve such a problem, and was shown to achieve the optimal complexity dependence on the required accuracy level $\epsilon$. Despite the superior theoretical performance, the convergence guarantee of SREDA requires stringent initialization accuracy and an $\epsilon$-dependent stepsize for controlling the per-iteration progress, so that SREDA can run very slowly in practice. This paper develops a novel analytical framework that guarantees the SREDA's optimal complexity performance for a much enhanced algorithm SREDA-Boost, which has less restrictive initialization requirement and an accuracy-independent (and much bigger) stepsize. Hence, SREDA-Boost runs substantially faster in experiments than SREDA. We further apply SREDA-Boost to propose a zeroth-order variance reduction algorithm named ZO-SREDA-Boost for the scenario that has access only to the information about function values not gradients, and show that ZO-SREDA-Boost outperforms the best known complexity dependence on $\epsilon$. This is the first study that applies the variance reduction technique to zeroth-order algorithm for min-max optimization problems.

In this paper, we propose robust stochastic algorithms for solving convex compositional problems of the form $f(\E_\xi g(\cdot; \xi)) + r(\cdot)$ by establishing {\bf sub-Gaussian confidence bounds} under weak assumptions about the tails of noise distribution, i.e., {\bf heavy-tailed noise} with bounded second-order moments. One can achieve this goal by using an existing boosting strategy that boosts a low probability convergence result into a high probability result. However, piecing together existing results for solving compositional problems suffers from several drawbacks: (i) the boosting technique requires strong convexity of the objective; (ii) it requires a separate algorithm to handle non-smooth $r$; (iii) it also suffers from an additional polylogarithmic factor of the condition number. To address these issues, we directly develop a single-trial stochastic algorithm for minimizing optimal strongly convex compositional objectives, which has a nearly optimal high probability convergence result matching the lower bound of stochastic strongly convex optimization up to a logarithmic factor. To the best of our knowledge, this is the first work that establishes nearly optimal sub-Gaussian confidence bounds for compositional problems under heavy-tailed assumptions.

Proteins are made of atoms constantly fluctuating, but can occasionally undergo large-scale changes. Such transitions are of biological interest, linking the structure of a protein to its function with a cell. Atomic-level simulations, such as Molecular Dynamics (MD), are used to study these events. However, molecular dynamics simulations produce time series with multiple observables, while changes often only affect a few of them. Therefore, detecting conformational changes has proven to be challenging for most change-point detection algorithms. In this work, we focus on the identification of such events given many noisy observables. In particular, we show that the No-prior-Knowledge Exponential Weighted Moving Average (NEWMA) algorithm can be used along optical hardware to successfully identify these changes in real-time. Our method does not need to distinguish between the background of a protein and the protein itself. For larger simulations, it is faster than using traditional silicon hardware and has a lower memory footprint. This technique may enhance the sampling of the conformational space of molecules. It may also be used to detect change-points in other sequential data with a large number of features.