Learning the shape of protein microenvironments with a holographic convolutional neural network.

Proteins play a central role in biology from immune recognition to brain activity. While major advances in machine learning have improved our ability to predict protein structure from sequence, determining protein function from its sequence or structure remains a major challenge. Here, we introduce holographic convolutional neural network (H-CNN) for proteins, which is a physically motivated machine learning approach to model amino acid preferences in protein structures.

Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1.

Infusion of broadly neutralizing antibodies (bNAbs) has shown promise as an alternative to anti-retroviral therapy against HIV. A key challenge is to suppress viral escape, which is more effectively achieved with a combination of bNAbs. Here, we propose a computational approach to predict the efficacy of a bNAb therapy based on the population genetics of HIV escape, which we parametrize using high-throughput HIV sequence data from bNAb-naive patients.

Information-Geometric Optimization with Natural Selection.

Evolutionary algorithms, inspired by natural evolution, aim to optimize difficult objective functions without computing derivatives. Here we detail the relationship between classical population genetics of quantitative traits and evolutionary optimization, and formulate a new evolutionary algorithm. Optimization of a continuous objective function is analogous to searching for high fitness phenotypes on a fitness landscape.

Correspondence between thermodynamics and inference.

We expand upon a natural analogy between Bayesian statistics and statistical physics in which sample size corresponds to inverse temperature. This analogy motivates the definition of two statistical quantities: a learning capacity and a Gibbs entropy. The analysis of the learning capacity, corresponding to the heat capacity in thermal physics, leads to insight into the mechanism of learning and explains why some models have anomalously high learning performance.

The Development of an Information Criterion for Change-Point Analysis.

Change-point analysis is a flexible and computationally tractable tool for the analysis of times series data from systems that transition between discrete states and whose observables are corrupted by noise. The change point algorithm is used to identify the time indices (change points) at which the system transitions between these discrete states. We present a unified information-based approach to testing for the existence of change points.