Georgia Institute of Technology School of Mathematics | Georgia Institute of Technology | Atlanta, GA

In quantum mechanics and the analysis of Markov processes, Monte Carlo methods are needed to identify low-lying eigenfunctions of dynamical generators. The standard Monte Carlo approaches for identifying eigenfunctions, however, can be inaccurate or slow to converge. What limits the efficiency of the currently available spectral estimation methods and what is needed to build more efficient methods for the future? Through numerical analysis and computational examples, we begin to answer these questions. We present the first-ever convergence proof and error bounds for the variational approach to conformational dynamics (VAC), the dominant method for estimating eigenfunctions used in biochemistry. Additionally, we analyze and optimize variational Monte Carlo (VMC), which combines Monte Carlo with neural networks to accurately identify low-lying eigenstates of quantum systems.

Neural network-based machine learning methods, inlcuding the most notably deep learning have achieved extraordinary successes in numerious  fields. In spite of the rapid development of learning algorithms based on neural networks, their mathematical analysis are far from understood. In particular, it has been a big mystery that neural network-based machine learning methods work extremely well for solving high dimensional problems.

In this talk, I will demonstrate the power of  neural network methods for solving two classes of high dimensional problems: statistical sampling and PDEs. In the first part of the talk, I will present a universal approximation theorem of deep neural networks for representing high dimensional probability distributions. In the second part of the talk, I will discuss a generalization error bound of the Deep Ritz Method for solving high dimensional elliptic problems. For both problems,  our theoretical results show that neural networks-based methods  can overcome the curse of dimensionality.

Cryo-Electron Microscopy (cryo-EM) is an imaging technology that is revolutionizing structural biology. Cryo-electron microscopes produce a large number of very noisy two-dimensional projection images of individual frozen molecules; unlike related methods, such as computed tomography (CT), the viewing direction of each particle image is unknown. The unknown directions, together with extreme levels of noise and additional technical factors, make the determination of the structure of molecules challenging. While other methods for structure determination, such as x-ray crystallography and nuclear magnetic resonance (NMR), measure ensembles of molecules, cryo-electron microscopes produce images of individual molecules. Therefore, cryo-EM could potentially be used to study mixtures of different conformations of molecules. Indeed, current algorithms have been very successful at analyzing homogeneous samples, and can recover some distinct conformations mixed in solutions, but, the determination of multiple conformations, and in particular, continuums of similar conformations (continuous heterogeneity), remains one of the open problems in cryo-EM. In practice, some of the key components in “molecular machines” are flexible and therefore appear as very blurry regions in 3-D reconstructions of macro-molecular structures that are otherwise stunning in resolution and detail.

We will discuss “hyper-molecules,” the mathematical formulation of heterogenous 3-D objects as higher dimensional objects, and the machinery that goes into recovering these “hyper-objects” from data. We will discuss some of the statistical and computational challenges, and how they are addressed by merging data-driven exploration, models and computational tools originally built for deep-learning.

This is joint work with Joakim Andén and Amit Singer.

Deep learning has achieved great success in recent years. One aspect overlooked by traditional deep-learning methods is uncertainty modeling, which can be very important in certain applications such as medical image classification and reinforcement learning. A standard way for uncertainty modeling is by adopting Bayesian inference. In this talk, I will share some of our recent work on scalable Bayesian inference by sampling, called optimal-transport sampling, motivated from the optimal-transport theory. Our framework formulates Bayesian sampling as optimizing a set of particles, overcoming some intrinsic issues of standard Bayesian sampling algorithms such as sampling efficiency and algorithm scalability. I will also describe how our sampling framework be applied to uncertainty and repulsive attention modeling in state-of-the-art natural-language-processing models.

https://bluejeans.com/197711728