title: Scalable inference of heterogeneous reaction kinetics from pooled single-cell recordings.
abstract: Mathematical methods combined with measurements of single-cell dynamics provide a means to reconstruct intracellular processes that are only partly or indirectly accessible experimentally. To obtain reliable reconstructions, the pooling of measurements from several cells of a clonal population is mandatory. However, cell-to-cell variability originating from diverse sources poses computational challenges for such process reconstruction. We introduce a scalable Bayesian inference framework that properly accounts for population heterogeneity. The method allows inference of inaccessible molecular states and kinetic parameters; computation of Bayes factors for model selection; and dissection of intrinsic, extrinsic and technical noise. We show how additional single-cell readouts such as morphological features can be included in the analysis. We use the method to reconstruct the expression dynamics of a gene under an inducible promoter in yeast from time-lapse microscopy data.
authors.affiliation: Automatic Control Lab, ETH Zurich, Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Zechner
authors.affiliation: 1] Automatic Control Lab, ETH Zurich, Zurich, Switzerland. [2] Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Unger
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Serge
authors.initials: S
authors.lastname: Pelet
authors.affiliation: Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
authors.affiliation: 1] Automatic Control Lab, ETH Zurich, Zurich, Switzerland. [2] IBM Zurich Research Laboratory, Rueschlikon, Switzerland. [3].
authors.forename: Heinz
authors.initials: H
authors.lastname: Koeppl
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D002468:Cell Physiological Phenomena; D003198:Computer Simulation; D005686:Galactokinase / Q000235:genetics / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008164:Luminescent Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009010:Monte Carlo Method; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013269:Stochastic Processes
chemical_list: D008164:Luminescent Proteins; D029701:Saccharomyces cerevisiae Proteins; C524219:GAL1 protein, S cerevisiae; D005686:Galactokinase