Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
Ann Biomed Eng. 2012 Nov;40(11):2319-27. doi: 10.1007/s10439-012-0560-1. Epub 2012 Apr 3.
Computational models of signal transduction face challenges of scale below the resolution of a single cell. Here, we organize these challenges around three key interfaces for multiscale models of cell signaling: molecules to pathways, pathways to networks, and networks to outcomes. Each interface requires its own set of computational approaches and systems-level data, and no single approach or dataset can effectively bridge all three interfaces. This suggests that realistic "whole-cell" models of signaling will need to agglomerate different model types that span critical intracellular scales. Future multiscale models will be valuable for understanding the impact of signaling mutations or population variants that lead to cellular diseases such as cancer.
信号转导的计算模型面临着单个细胞分辨率以下的规模挑战。在这里，我们围绕细胞信号转导多尺度模型的三个关键接口来组织这些挑战：分子到途径、途径到网络和网络到结果。每个接口都需要自己的计算方法和系统级数据，没有单一的方法或数据集可以有效地连接这三个接口。这表明，现实的“全细胞”信号模型将需要聚集跨越关键细胞内尺度的不同模型类型。未来的多尺度模型对于理解导致癌症等细胞疾病的信号突变或群体变异的影响将非常有价值。
