RT Journal Article
SR Electronic
T1 One model fits all: combining inference and simulation of gene regulatory networks
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.19.496754
DO 10.1101/2022.06.19.496754
A1 Elias Ventre
A1 Ulysse Herbach
A1 Thibault Espinasse
A1 Gérard Benoit
A1 Olivier Gandrillon
YR 2022
UL http://biorxiv.org/content/early/2022/06/20/2022.06.19.496754.abstract
AB The rise of single-cell data highlights the need for a nondeterministic view of gene expression, while offering new opportunities regarding gene regulatory network inference. We recently introduced two strategies that specifically exploit time-course data, where single-cell profiling is performed after a stimulus: HARISSA, a mechanistic network model with a highly efficient simulation procedure, and CARDAMOM, a scalable inference method seen as model calibration. Here, we combine the two approaches and show that the same model driven by transcriptional bursting can be used simultaneously as an inference tool, to reconstruct biologically relevant networks, and as a simulation tool, to generate realistic transcriptional profiles emerging from gene interactions. We verify that CARDAMOM quantitatively reconstructs causal links when the data is simulated from HARISSA, and demonstrate its performance on experimental data collected on in vitro differentiating mouse embryonic stem cells. Overall, this integrated strategy largely overcomes the limitations of disconnected inference and simulation.Competing Interest StatementThe authors have declared no competing interest.