Format

Send to

Choose Destination
Bioinformatics. 2015 Jun 15;31(12):i89-96. doi: 10.1093/bioinformatics/btv257.

Reconstructing gene regulatory dynamics from high-dimensional single-cell snapshot data.

Author information

1
Institute of Computational Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany and Department of Mathematics, Technical University Munich, 85747 Garching, Germany.
2
Institute of Computational Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany and Department of Mathematics, Technical University Munich, 85747 Garching, Germany Institute of Computational Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany and Department of Mathematics, Technical University Munich, 85747 Garching, Germany.

Abstract

MOTIVATION:

High-dimensional single-cell snapshot data are becoming widespread in the systems biology community, as a mean to understand biological processes at the cellular level. However, as temporal information is lost with such data, mathematical models have been limited to capture only static features of the underlying cellular mechanisms.

RESULTS:

Here, we present a modular framework which allows to recover the temporal behaviour from single-cell snapshot data and reverse engineer the dynamics of gene expression. The framework combines a dimensionality reduction method with a cell time-ordering algorithm to generate pseudo time-series observations. These are in turn used to learn transcriptional ODE models and do model selection on structural network features. We apply it on synthetic data and then on real hematopoietic stem cells data, to reconstruct gene expression dynamics during differentiation pathways and infer the structure of a key gene regulatory network.

AVAILABILITY AND IMPLEMENTATION:

C++ and Matlab code available at https://www.helmholtz-muenchen.de/fileadmin/ICB/software/inferenceSnapshot.zip.

PMID:
26072513
PMCID:
PMC4765871
DOI:
10.1093/bioinformatics/btv257
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center