HopLand: single-cell pseudotime recovery using continuous Hopfield network-based modeling of Waddington's epigenetic landscape.

Abstract

The interpretation of transcriptional dynamics in single-cell data, especially pseudotime estimation, could help understand the transition of gene expression profiles. The recovery of pseudotime increases the temporal resolution of single-cell transcriptional data, but is challenging due to the high variability in gene expression between individual cells. Here, we introduce HopLand, a pseudotime recovery method using continuous Hopfield network to map cells to a Waddington's epigenetic landscape. It reveals from the single-cell data the combinatorial regulatory interactions among genes that control the dynamic progression through successive cell states. We applied HopLand to different types of single-cell transcriptomic data. It achieved high accuracies of pseudotime prediction compared with existing methods. Moreover, a kinetic model can be extracted from each dataset. Through the analysis of such a model, we identified key genes and regulatory interactions driving the transition of cell states. Therefore, our method has the potential to generate fundamental insights into cell fate regulation. The MATLAB implementation of HopLand is available at https://github.com/NetLand-NTU/HopLand . zhengjie@ntu.edu.sg.