title: Summary of the DREAM8 Parameter Estimation Challenge: Toward Parameter Identification for Whole-Cell Models.
abstract: Whole-cell models that explicitly represent all cellular components at the molecular level have the potential to predict phenotype from genotype. However, even for simple bacteria, whole-cell models will contain thousands of parameters, many of which are poorly characterized or unknown. New algorithms are needed to estimate these parameters and enable researchers to build increasingly comprehensive models. We organized the Dialogue for Reverse Engineering Assessments and Methods (DREAM) 8 Whole-Cell Parameter Estimation Challenge to develop new parameter estimation algorithms for whole-cell models. We asked participants to identify a subset of parameters of a whole-cell model given the model's structure and in silico "experimental" data. Here we describe the challenge, the best performing methods, and new insights into the identifiability of whole-cell models. We also describe several valuable lessons we learned toward improving future challenges. Going forward, we believe that collaborative efforts supported by inexpensive cloud computing have the potential to solve whole-cell model parameter estimation.
authors.affiliation: Graduate Program in Biophysics, Stanford University, Stanford, California, United States of America.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Karr
authors.affiliation: Department of Biology, Brandeis University, Waltham, Massachusetts, United States of America; Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts, United States of America.
authors.forename: Alex H
authors.initials: AH
authors.lastname: Williams
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Zucker
authors.affiliation: Institute for Physics, University of Freiburg, Freiburg, Germany; Freiburg Center for Systems Biology (ZBSA), University of Freiburg, Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Raue
authors.affiliation: Institute for Physics, University of Freiburg, Freiburg, Germany; Freiburg Center for Systems Biology (ZBSA), University of Freiburg, Freiburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Steiert
authors.affiliation: Institute for Physics, University of Freiburg, Freiburg, Germany; Freiburg Center for Systems Biology (ZBSA), University of Freiburg, Freiburg, Germany; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Timmer
authors.affiliation: Institute for Physics, University of Freiburg, Freiburg, Germany; Freiburg Center for Systems Biology (ZBSA), University of Freiburg, Freiburg, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Kreutz
authors.affiliation: Numerate Inc., San Bruno, California, United States of America.
authors.forename: Simon
authors.initials: S
authors.lastname: Wilkinson
authors.affiliation: Numerate Inc., San Bruno, California, United States of America.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Allgood
authors.affiliation: Sage Bionetworks, Seattle, Washington, United States of America.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Bot
authors.affiliation: Sage Bionetworks, Seattle, Washington, United States of America.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Hoff
authors.affiliation: Sage Bionetworks, Seattle, Washington, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kellen
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California, United States of America.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Covert
authors.affiliation: IBM Thomas J. Watson Research Center, Yorktown Heights, New York, United States of America.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Stolovitzky
authors.affiliation: IBM Thomas J. Watson Research Center, Yorktown Heights, New York, United States of America.
authors.forename: Pablo
authors.initials: P
authors.lastname: Meyer
mesh_terms: D000465:Algorithms; D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D057005:Bioengineering; D002477:Cells / Q000378:metabolism*; D000067917:Cloud Computing; D019295:Computational Biology; D003198:Computer Simulation; D056726:Genetic Association Studies / Q000706:statistics & numerical data; D008954:Models, Biological; D009154:Mutation; D045704:Mycoplasma genitalium / Q000235:genetics / Q000378:metabolism