Lagomarsino Marco Cosentino, Bassetti Bruno, Castellani Gastone, Remondini Daniel
Università degli Studi di Milano, Dip. Fisica. Via Celoria 16, 20133 Milano, Italy.
Mol Biosyst. 2009 Apr;5(4):335-44. doi: 10.1039/b816841p. Epub 2009 Jan 30.
High-throughput experiments are shedding light on the topology of large regulatory networks and at the same time their functional states, namely the states of activation of the nodes (for example transcript or protein levels) in different conditions, times, environments. We now possess a certain amount of information about these two levels of description, stored in libraries, databases and ontologies. A current challenge is to bridge the gap between topology and function, i.e. developing quantitative models aimed at characterizing the expression patterns of large sets of genes. However, approaches that work well for small networks become impossible to master at large scales, mainly because parameters proliferate. In this review we discuss the state of the art of large-scale functional network models, addressing the issue of what can be considered as "realistic" and what the main limitations may be. We also show some directions for future work, trying to set the goals that future models should try to achieve. Finally, we will emphasize the possible benefits in the understanding of biological mechanisms underlying complex multifactorial diseases, and in the development of novel strategies for the description and the treatment of such pathologies.
高通量实验正在揭示大型调控网络的拓扑结构,同时也在揭示其功能状态,即在不同条件、时间和环境下节点(例如转录本或蛋白质水平)的激活状态。我们现在已经拥有了关于这两个描述层面的一定量信息,这些信息存储在文库、数据库和本体中。当前的一个挑战是弥合拓扑结构与功能之间的差距,即开发旨在表征大量基因表达模式的定量模型。然而,适用于小型网络的方法在大规模情况下变得难以掌控,主要是因为参数激增。在这篇综述中,我们讨论了大规模功能网络模型的现状,探讨了哪些可以被视为“现实的”以及主要局限性可能是什么。我们还展示了未来工作的一些方向,试图设定未来模型应努力实现的目标。最后,我们将强调在理解复杂多因素疾病背后的生物学机制以及开发描述和治疗此类病症的新策略方面可能带来的益处。