Discriminating direct and indirect connectivities in biological networks
Discriminating direct and indirect connectivities in biological networks
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DOI：
10.1073/pnas.1507168112
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发表时间：
2015-10-13
影响因子：
11.1
通讯作者：
Bleris, Leonidas
中科院分区：
文献类型：
--
作者：
Kang, Taek;Moore, Richard;Bleris, Leonidas
生物途径的逆向工程涉及实验、数据处理和理论分析之间的迭代过程。尽管在数据的质量和数量以及计算资源和算法方面同时取得了进步，但破译直接和间接网络连接的困难仍然普遍存在。在这里，我们采用了抽象，仿真，基准测试和验证的概念，在发现特定于这个家庭的连接功能的上下文中。在基准合成电路受到扰动后，我们使用非参数单细胞数据恢复和模块化响应分析的组合来推断网络连接。有趣的是，我们发现特定网络边缘的恢复权重在微分扰动下发生发散性变化，并且拓扑结构之间的特定行为明显不同。我们的研究结果指出了一个概念上的进步，逆向工程超越重量推断。研究微分扰动下的拓扑变化可以解决生物网络中区分直接和间接连通性的长期问题。
Reverse engineering of biological pathways involves an iterative process between experiments, data processing, and theoretical analysis. Despite concurrent advances in quality and quantity of data as well as computing resources and algorithms, difficulties in deciphering direct and indirect network connections are prevalent. Here, we adopt the notions of abstraction, emulation, benchmarking, and validation in the context of discovering features specific to this family of connectivities. After subjecting benchmark synthetic circuits to perturbations, we inferred the network connections using a combination of non-parametric single-cell data resampling and modular response analysis. Intriguingly, we discovered that recovered weights of specific network edges undergo divergent shifts under differential perturbations, and that the particular behavior is markedly different between topologies. Our results point to a conceptual advance for reverse engineering beyond weight inference. Investigating topological changes under differential perturbations may address the longstanding problem of discriminating direct and indirect connectivities in biological networks.