Inheritance and variability of kinetic gene expression parameters in microbial cells: modeling and inference from lineage tree data

Aline Marguet 1 Marc Lavielle 2 Eugenio Cinquemani 1
1 IBIS - Modeling, simulation, measurement, and control of bacterial regulatory networks
LAPM - Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble], Inria Grenoble - Rhône-Alpes, Institut Jean Roget
Abstract : Motivation: Modern experimental technologies enable monitoring of gene expression dynamics in individual cells and quantification of its variability in isogenic microbial populations. Among the sources of this variability is the randomness that affects inheritance of gene expression factors at cell division. Known parental relationships among individually observed cells provide invaluable information for the characterization of this extrinsic source of gene expression noise. Despite this fact, most existing methods to infer stochastic gene expression models from single-cell data dedicate little attention to the reconstruction of mother-daughter inheritance dynamics. Results: Starting from a transcription and translation model of gene expression, we propose a sto-chastic model for the evolution of gene expression dynamics in a population of dividing cells. Based on this model, we develop a method for the direct quantification of inheritance and variability of kinetic gene expression parameters from single-cell gene expression and lineage data. We demonstrate that our approach provides unbiased estimates of mother-daughter inheritance parameters, whereas indirect approaches using lineage information only in the post-processing of individual-cell parameters underestimate inheritance. Finally, we show on yeast osmotic shock response data that daughter cell parameters are largely determined by the mother, thus confirming the relevance of our method for the correct assessment of the onset of gene expression variability and the study of the transmission of regulatory factors. Availability and implementation: Software code is available at https://github.com/almarguet/IdentificationWithARME. Lineage tree data is available upon request.
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Submitted on : Tuesday, October 15, 2019 - 6:56:27 PM
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Aline Marguet, Marc Lavielle, Eugenio Cinquemani. Inheritance and variability of kinetic gene expression parameters in microbial cells: modeling and inference from lineage tree data. Bioinformatics, Oxford University Press (OUP), 2019, 35 (14), pp.i586-i595. ⟨10.1093/bioinformatics/btz378⟩. ⟨hal-02317115⟩

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