16 accepted papers
Many methods have been developed to predict static protein structures, however understanding the dynamics of protein structure is essential for elucidating biological function. While molecular dynamics (MD) simulations remain the in silico gold standard, its high computational cost limits scalabilit…
Multistate mechanisms underlie many of the complex functions observed in natural proteins. The ability to rationally design multistate proteins would have transformative implications for many areas of biotechnology, yet lies beyond the capabilities of existing deep learning frameworks for protein de…
Graph neural networks (GNNs) are widely used in urban spatiotemporal forecasting, e.g., predicting infrastructure problems. In this setting, government officials aim to identify in which neighborhoods incidents like potholes or rodents occur. The true state of incidents is observed via government in
It is difficult to evaluate machine learning classifiers without large labeled datasets, which are often unavailable. In contrast, unlabeled data is plentiful, but not easily used for evaluation. Here, we introduce Semi-Supervised Model Evaluation (SSME), a method that uses both labeled and unlabel…
The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly accurate single-state predictors such as AlphaFold and ESMFol…
Discrete diffusion or flow models could enable faster and more controllable sequence generation than autoregressive models. We show that naive linear flow matching on the simplex is insufficient toward this goal since it suffers from discontinuities in the training target and further pathologies. To…
Molecular docking is critical to structure-based virtual screening, yet the throughput of such workflows is limited by the expensive optimization of scoring functions involved in most docking algorithms. We explore how machine learning can accelerate this process by learning a scoring function with…
Molecular dynamics (MD) is a powerful technique for studying microscopic phenomena, but its computational cost has driven significant interest in the development of deep learning-based surrogate models. We introduce generative modeling of molecular trajectories as a paradigm for learning flexible mu…
When a dynamical system can be modeled as a sequence of observations, Granger causality is a powerful approach for detecting predictive interactions between its variables. However, traditional Granger causal inference has limited utility in domains where the dynamics need to be represented as direct…
Protein structure determination from cryo-EM data requires reconstructing a 3D volume (or distribution of volumes) from many noisy and randomly oriented 2D projection images. While the standard homogeneous reconstruction task aims to recover a single static structure, recently-proposed neural and no…
Detection of cancer-causing mutations within the vast and mostly unexplored human genome is a major challenge. Doing so requires modeling the background mutation rate, a highly non-stationary stochastic process, across regions of interest varying in size from one to millions of positions. Here, we p…
In many natural domains, changing a small part of an entity can transform its semantics; for example, a single word change can alter the meaning of a sentence, or a single amino acid change can mutate a viral protein to escape antiviral treatment or immunity. Although identifying such mutations can…
Cryo-electron microscopy (cryo-EM) is a powerful technique for determining the structure of proteins and other macromolecular complexes at near-atomic resolution. In single particle cryo-EM, the central problem is to reconstruct the 3D structure of a macromolecule from $10^{4-7}$ noisy and randomly…
Given an image dataset, we are often interested in finding data generative factors that encode semantic content independently from pose variables such as rotation and translation. However, current disentanglement approaches do not impose any specific structure on the learned latent representations.…
Representing data in hyperbolic space can effectively capture latent hierarchical relationships. To enable accurate classification of points in hyperbolic space while respecting their hyperbolic geometry, we introduce hyperbolic SVM, a hyperbolic formulation of support vector machine classifiers, an…
Inferring the structural properties of a protein from its amino acid sequence is a challenging yet important problem in biology. Structures are not known for the vast majority of protein sequences, but structure is critical for understanding function. Existing approaches for detecting structural sim…