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Bioinformatics. 2017 Jul 15;33(14):i102-i109. doi: 10.1093/bioinformatics/btx232.

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

Guo J1,2, Zheng J1,3,4.

Author information

1
Biomedical Informatics Laboratory, School of Computer Science and Engineering, Nanyang Technological University, Singapore, Singapore.
2
Bioinformatics Institute, Agency for Science, Technology, and Research (A*STAR), Singapore, Singapore.
3
Genome Institute of Singapore, Agency for Science, Technology, and Research (A*STAR), Singapore, Singapore.
4
Complexity Institute, Nanyang Technological University, Singapore, Singapore.

Abstract

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 .

Contact:

zhengjie@ntu.edu.sg.

PMID:
28881967
PMCID:
PMC5870541
DOI:
10.1093/bioinformatics/btx232
[Indexed for MEDLINE]
Free PMC Article

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