title: Robust reconstruction of gene expression profiles from reporter gene data using linear inversion.
abstract: BACKGROUND
  Time-series observations from reporter gene experiments are commonly used for inferring and analyzing dynamical models of regulatory networks. The robust estimation of promoter activities and protein concentrations from primary data is a difficult problem due to measurement noise and the indirect relation between the measurements and quantities of biological interest.
  
  
  RESULTS
  We propose a general approach based on regularized linear inversion to solve a range of estimation problems in the analysis of reporter gene data, notably the inference of growth rate, promoter activity, and protein concentration profiles. We evaluate the validity of the approach using in silico simulation studies, and observe that the methods are more robust and less biased than indirect approaches usually encountered in the experimental literature based on smoothing and subsequent processing of the primary data. We apply the methods to the analysis of fluorescent reporter gene data acquired in kinetic experiments with Escherichia coli. The methods are capable of reliably reconstructing time-course profiles of growth rate, promoter activity and protein concentration from weak and noisy signals at low population volumes. Moreover, they capture critical features of those profiles, notably rapid changes in gene expression during growth transitions.
  
  
  METHODS
  The methods described in this article are made available as a Python package (LGPL license) and also accessible through a web interface. For more information, see https://team.inria.fr/ibis/wellinverter.
authors.affiliation: INRIA Grenoble-Rhône-Alpes, 655 Avenue de l'Europe, Montbonnot, 38334 Saint-Ismier Cedex, France, IAE Grenoble, Université Pierre-Mendès-France, Domaine universitaire BP 47, Grenoble Cedex 9, 38040 Saint Martin d'Hères, France and Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Université Joseph Fourier, 140 Avenue de la physique BP 87, 38402 Saint Martin d'Hères, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: Zulkower
authors.affiliation: INRIA Grenoble-Rhône-Alpes, 655 Avenue de l'Europe, Montbonnot, 38334 Saint-Ismier Cedex, France, IAE Grenoble, Université Pierre-Mendès-France, Domaine universitaire BP 47, Grenoble Cedex 9, 38040 Saint Martin d'Hères, France and Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Université Joseph Fourier, 140 Avenue de la physique BP 87, 38402 Saint Martin d'Hères, France INRIA Grenoble-Rhône-Alpes, 655 Avenue de l'Europe, Montbonnot, 38334 Saint-Ismier Cedex, France, IAE Grenoble, Université Pierre-Mendès-France, Domaine universitaire BP 47, Grenoble Cedex 9, 38040 Saint Martin d'Hères, France and Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Université Joseph Fourier, 140 Avenue de la physique BP 87, 38402 Saint Martin d'Hères, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Page
authors.affiliation: INRIA Grenoble-Rhône-Alpes, 655 Avenue de l'Europe, Montbonnot, 38334 Saint-Ismier Cedex, France, IAE Grenoble, Université Pierre-Mendès-France, Domaine universitaire BP 47, Grenoble Cedex 9, 38040 Saint Martin d'Hères, France and Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Université Joseph Fourier, 140 Avenue de la physique BP 87, 38402 Saint Martin d'Hères, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Ropers
authors.affiliation: INRIA Grenoble-Rhône-Alpes, 655 Avenue de l'Europe, Montbonnot, 38334 Saint-Ismier Cedex, France, IAE Grenoble, Université Pierre-Mendès-France, Domaine universitaire BP 47, Grenoble Cedex 9, 38040 Saint Martin d'Hères, France and Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Université Joseph Fourier, 140 Avenue de la physique BP 87, 38402 Saint Martin d'Hères, France INRIA Grenoble-Rhône-Alpes, 655 Avenue de l'Europe, Montbonnot, 38334 Saint-Ismier Cedex, France, IAE Grenoble, Université Pierre-Mendès-France, Domaine universitaire BP 47, Grenoble Cedex 9, 38040 Saint Martin d'Hères, France and Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Université Joseph Fourier, 140 Avenue de la physique BP 87, 38402 Saint Martin d'Hères, France.
authors.forename: Johannes
authors.initials: J
authors.lastname: Geiselmann
authors.affiliation: INRIA Grenoble-Rhône-Alpes, 655 Avenue de l'Europe, Montbonnot, 38334 Saint-Ismier Cedex, France, IAE Grenoble, Université Pierre-Mendès-France, Domaine universitaire BP 47, Grenoble Cedex 9, 38040 Saint Martin d'Hères, France and Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Université Joseph Fourier, 140 Avenue de la physique BP 87, 38402 Saint Martin d'Hères, France.
authors.forename: Hidde
authors.initials: H
authors.lastname: de Jong
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics*; D007700:Kinetics; D012044:Regression Analysis
chemical_list: D029968:Escherichia coli Proteins