Network depth affects inference of gene sets from bacterial transcriptomes using denoising autoencoders.

Summary: The increasing number of publicly available bacterial gene expression data sets provides an unprecedented resource for the study of gene regulation in diverse conditions, but emphasizes the need for self-supervised methods for the automated generation of new hypotheses. One approach for inferring coordinated regulation from bacterial expression data is through neural networks known as denoising autoencoders (DAEs) which encode large datasets in a reduced bottleneck layer. We have generalized this application of DAEs to include deep networks and explore the effects of network architecture on gene set inference using deep learning. We developed a DAE-based pipeline to extract gene sets from transcriptomic data in Escherichia coli, validate our method by comparing inferred gene sets with known pathways, and have used this pipeline to explore how the choice of network architecture impacts gene set recovery. We find that increasing network depth leads the DAEs to explain gene expression in terms of fewer, more concisely defined gene sets, and that adjusting the width results in a tradeoff between generalizability and biological inference. Finally, leveraging our understanding of the impact of DAE architecture, we apply our pipeline to an independent uropathogenic E.coli dataset to identify genes uniquely induced during human colonization.

Availability and implementation: https://github.com/BarquistLab/DAE_architecture_exploration.