RIKEN Center for Biosystems Dynamics Research, Osaka, Japan.
Dev Growth Differ. 2023 Dec;65(9):554-564. doi: 10.1111/dgd.12897. Epub 2023 Nov 8.
With 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.
随着高通量、大规模体内测量和单核苷酸水平基因组修饰技术的进步，人们对灵活设计和控制细胞系统的新技术的需求不断增加。计算机辅助设计是设计新细胞的有力工具。全细胞建模旨在整合各种细胞子系统，通过在全基因组范围内进行计算模拟来确定它们的相互作用和协同机制，并预测全面的细胞行为。它已应用于原核生物、酵母和高等真核细胞，并广泛应用于生产有价值的物质、药物发现和受控分化等领域。全细胞建模由具有不同尺度和特性的数千个元素组成，需要创新的模型构建、模拟和分析技术。此外，全细胞建模已经扩展到多个尺度，包括单核苷酸和单氨基酸水平的高分辨率建模以及组织和器官的多细胞建模。本文综述了全细胞建模的现状，讨论了推动其发展的新型计算和实验技术，并介绍了朝着全基因组尺度多层次建模的进一步发展。
