Recovering time-varying networks from single-cell data.

motivationGene regulation is a dynamic process that underlies all aspects of human development, disease response, and other biological processes. The reconstruction of temporal gene regulatory networks has conventionally relied on regression analysis, graphical models, or other types of relevance networks. With the large increase in time series single-cell data, new approaches are needed to address the unique scale and nature of these data for reconstructing such networks.

resultsHere, we develop a deep neural network, Marlene, to infer dynamic graphs from time series single-cell gene expression data. Marlene constructs directed gene networks using a self-attention mechanism where the weights evolve over time using recurrent units. By employing meta learning, the model is able to recover accurate temporal networks even for rare cell types. In addition, Marlene can identify gene interactions relevant to specific biological responses, including COVID-19 immune response, fibrosis, and aging, paving the way for potential treatments. AVAILABILITY AND IMPLEMENTATION: The code used to train Marlene is available at https://github.com/euxhenh/Marlene.