title: The principles of whole-cell modeling.
abstract: Whole-cell models which comprehensively predict how phenotypes emerge from genotype promise to enable rational bioengineering and precision medicine. Here, we outline the key principles of whole-cell modeling which have emerged from our work developing bacterial whole-cell models: single-cellularity; functional, genetic, molecular, and temporal completeness; biophysical realism including temporal dynamics and stochastic variation; species-specificity; and model integration and reproducibility. We also outline the whole-cell model construction process, highlighting existing resources. Numerous challenges remain to achieving fully complete models including developing new experimental tools to more completely characterize cells and developing a strong theoretical understanding of hybrid mathematics. Solving these challenges requires collaboration among computational and experimental biologists, biophysicists, biochemists, applied mathematicians, computer scientists, and software engineers.
authors.affiliation: Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: karr@mssm.edu.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Karr
authors.affiliation: RIKEN Quantitative Biology Center, RIKEN, Osaka 565-0874, Japan; Institute for Advanced Biosciences, Keio University, Fujisawa 252-8520, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Biosciences and Informatics, Keio University, Yokohama 223-8522, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Funahashi
mesh_terms: D001419:Bacteria; D018407:Bacterial Physiological Phenomena; D057005:Bioengineering; D002468:Cell Physiological Phenomena; D002477:Cells; D003198:Computer Simulation; D008954:Models, Biological; D008967:Molecular Biology / Q000379:methods*; D059010:Single-Cell Analysis