Graduate Program in Biophysics, Stanford University, Stanford, CA 94305, USA.
Cell. 2012 Jul 20;150(2):389-401. doi: 10.1016/j.cell.2012.05.044.
Understanding how complex phenotypes arise from individual molecules and their interactions is a primary challenge in biology that computational approaches are poised to tackle. We report a whole-cell computational model of the life cycle of the human pathogen Mycoplasma genitalium that includes all of its molecular components and their interactions. An integrative approach to modeling that combines diverse mathematics enabled the simultaneous inclusion of fundamentally different cellular processes and experimental measurements. Our whole-cell model accounts for all annotated gene functions and was validated against a broad range of data. The model provides insights into many previously unobserved cellular behaviors, including in vivo rates of protein-DNA association and an inverse relationship between the durations of DNA replication initiation and replication. In addition, experimental analysis directed by model predictions identified previously undetected kinetic parameters and biological functions. We conclude that comprehensive whole-cell models can be used to facilitate biological discovery.
理解复杂表型如何从单个分子及其相互作用中产生，是生物学面临的主要挑战之一，而计算方法正准备解决这一挑战。我们报告了一种人类病原体生殖道支原体生命周期的全细胞计算模型，其中包括其所有的分子成分及其相互作用。一种综合的建模方法，结合了不同的数学方法，使基本不同的细胞过程和实验测量能够同时包含在内。我们的全细胞模型解释了所有注释的基因功能，并针对广泛的数据集进行了验证。该模型提供了对许多以前未观察到的细胞行为的深入了解，包括体内蛋白质-DNA 结合的速率以及 DNA 复制起始和复制持续时间之间的反比关系。此外，受模型预测指导的实验分析确定了以前未检测到的动力学参数和生物学功能。我们得出结论，全面的全细胞模型可用于促进生物学发现。
