arXiv subjects

Daniel Zilber

Publications and source records attributed to Daniel Zilber.

3 recordsLinked to original sources

arXiv2025

Leveraging ontologies to predict biological activity of chemicals across genes

High-throughput screening (HTS) is useful for evaluating chemicals for potential human health risks. However, given the extraordinarily large number of genes, assay endpoints, and chemicals of interest, available data are sparse, with dose-response curves missing for the vast majority of chemical-gene pairs. Although gene ontologies characterize similarity among genes with respect to known cellular functions and biological pathways, the sensitivity of various pathways to environmental contaminants remains unclear. We propose a novel Dose-Activity Response Tracking (DART) approach to predict the biological activity of chemicals across genes using information on chemical structural properties and gene ontologies within a Bayesian factor model. Designed to provide toxicologists with a flexible tool applicable across diverse HTS assay platforms, DART reveals the latent processes driving dose-response behavior and predicts new activity profiles for chemical-gene pairs lacking experimental data. We demonstrate the performance of DART through simulation studies and an application to a vast new multi-experiment data set consisting of dose-response observations generated by the exposure of HepG2 cells to per- and polyfluoroalkyl substances (PFAS), where it provides actionable guidance for chemical prioritization and inference on the structural and functional mechanisms underlying assay activation.

stat.AP↗

arXiv2020

Vecchia-Laplace approximations of generalized Gaussian processes for big non-Gaussian spatial data

Generalized Gaussian processes (GGPs) are highly flexible models that combine latent GPs with potentially non-Gaussian likelihoods from the exponential family. GGPs can be used in a variety of settings, including GP classification, nonparametric count regression, modeling non-Gaussian spatial data, and analyzing point patterns. However, inference for GGPs can be analytically intractable, and large datasets pose computational challenges due to the inversion of the GP covariance matrix. We propose a Vecchia-Laplace approximation for GGPs, which combines a Laplace approximation to the non-Gaussian likelihood with a computationally efficient Vecchia approximation to the GP, resulting in a simple, general, scalable, and accurate methodology. We provide numerical studies and comparisons on simulated and real spatial data. Our methods are implemented in a freely available R package.

stat.ME↗

arXiv2018

A class of multi-resolution approximations for large spatial datasets

Gaussian processes are popular and flexible models for spatial, temporal, and functional data, but they are computationally infeasible for large datasets. We discuss Gaussian-process approximations that use basis functions at multiple resolutions to achieve fast inference and that can (approximately) represent any spatial covariance structure. We consider two special cases of this multi-resolution-approximation framework, a taper version and a domain-partitioning (block) version. We describe theoretical properties and inference procedures, and study the computational complexity of the methods. Numerical comparisons and an application to satellite data are also provided.

stat.ME↗