Technologies for whole‐cell modeling: Genome‐wide reconstruction of a cell in silico

Abstract

AbstractWith advances in high‐throughput, large‐scale in vivo measurement and genome modification techniques at the single‐nucleotide level, there is an increasing demand for the development of new technologies for the flexible design and control of cellular systems. Computer‐aided design is a powerful tool to design new cells. Whole‐cell modeling aims to integrate various cellular subsystems, determine their interactions and cooperative mechanisms, and predict comprehensive cellular behaviors by computational simulations on a genome‐wide scale. It has been applied to prokaryotes, yeasts, and higher eukaryotic cells, and utilized in a wide range of applications, including production of valuable substances, drug discovery, and controlled differentiation. Whole‐cell modeling, consisting of several thousand elements with diverse scales and properties, requires innovative model construction, simulation, and analysis techniques. Furthermore, whole‐cell modeling has been extended to multiple scales, including high‐resolution modeling at the single‐nucleotide and single‐amino acid levels and multicellular modeling of tissues and organs. This review presents an overview of the current state of whole‐cell modeling, discusses the novel computational and experimental technologies driving it, and introduces further developments toward multihierarchical modeling on a whole‐genome scale.