Learning to encode cellular responses to systematic perturbations with deep generative models.

ABSTRACT: Cellular signaling systems play a vital role in maintaining homeostasis when a cell is exposed to different perturbations. Components of the systems are organized as hierarchical networks, and perturbing different components often leads to transcriptomic profiles that exhibit compositional statistical patterns. Mining such patterns to investigate how cellular signals are encoded is an important problem in systems biology, where artificial intelligence techniques can be of great assistance. Here, we investigated the capability of deep generative models (DGMs) to modeling signaling systems and learn representations of cellular states underlying transcriptomic responses to diverse perturbations. Specifically, we show that the variational autoencoder and the supervised vector-quantized variational autoencoder can accurately regenerate gene expression data in response to perturbagen treatments. The models can learn representations that reveal the relationships between different classes of perturbagens and enable mappings between drugs and their target genes. In summary, DGMs can adequately learn and depict how cellular signals are encoded. The resulting representations have broad applications, demonstrating the power of artificial intelligence in systems biology and precision medicine.

SUBMITTER: Xue Y 

PROVIDER: S-EPMC7648057 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature