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

MOTIVATION: 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. RESULTS: 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. AVAILABILITY AND IMPLEMENTATION: The MATLAB implementation of HopLand is available at https://github.com/NetLand-NTU/HopLand.