SYSBIO Centre of Systems Biology, Milan, Italy.
Department of Informatics, Systems and Communication, University Milano-Bicocca, Milan, Italy.
Bioinformatics. 2017 Jul 15;33(14):i311-i318. doi: 10.1093/bioinformatics/btx251.
Intratumour heterogeneity poses many challenges to the treatment of cancer. Unfortunately, the transcriptional and metabolic information retrieved by currently available computational and experimental techniques portrays the average behaviour of intermixed and heterogeneous cell subpopulations within a given tumour. Emerging single-cell genomic analyses are nonetheless unable to characterize the interactions among cancer subpopulations. In this study, we propose popFBA , an extension to classic Flux Balance Analysis, to explore how metabolic heterogeneity and cooperation phenomena affect the overall growth of cancer cell populations.
We show how clones of a metabolic network of human central carbon metabolism, sharing the same stoichiometry and capacity constraints, may follow several different metabolic paths and cooperate to maximize the growth of the total population. We also introduce a method to explore the space of possible interactions, given some constraints on plasma supply of nutrients. We illustrate how alternative nutrients in plasma supply and/or a dishomogeneous distribution of oxygen provision may affect the landscape of heterogeneous phenotypes. We finally provide a technique to identify the most proliferative cells within the heterogeneous population.
the popFBA MATLAB function and the SBML model are available at https://github.com/BIMIB-DISCo/popFBA .
肿瘤内异质性给癌症治疗带来了诸多挑战。遗憾的是，目前可用的计算和实验技术所获取的转录和代谢信息仅能描绘出给定肿瘤内混合和异质细胞亚群的平均行为。然而，新兴的单细胞基因组分析方法仍无法描述癌症亚群之间的相互作用。在本研究中，我们提出了 popFBA，这是对经典通量平衡分析的扩展，用于探索代谢异质性和合作现象如何影响癌细胞群体的整体生长。
我们展示了人类中心碳代谢代谢网络的克隆如何在共享相同化学计量和容量约束的情况下遵循几种不同的代谢途径并合作以最大化总群体的生长。我们还引入了一种方法来探索给定血浆供应营养素约束下的可能相互作用空间。我们说明了血浆供应中替代营养素和/或氧气供应的不均匀分布如何影响异质表型的景观。最后，我们提供了一种技术来识别异质群体中增殖能力最强的细胞。
popFBA 的 MATLAB 函数和 SBML 模型可在 https://github.com/BIMIB-DISCo/popFBA 上获得。
