CELLoGeNe - an Energy Landscape Framework for Logical Networks Controlling Cell Decisions
CELLoGeNe - an Energy Landscape Framework for Logical Networks Controlling Cell Decisions
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CELLoGeNe - 控制电池决策的逻辑网络的能源景观框架
DOI：
10.1101/2022.02.09.479734
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Andersson E
中科院分区：
文献类型：
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作者：
Andersson E
实验和计算的努力不断阐明机制控制细胞的命运决定在发展和重编程。一种强大的计算方法是将细胞承诺和重新编程视为能量景观中的运动。在这里，我们开发了逻辑基因网络的能量景观计算（CELLoGeNe），它将基因调控网络（GRNs）的布尔实现映射到能量景观中。CELLoGeNe消除了通常由标准布尔运算符产生的能量景观中的无意对称性。此外，CELLoGeNe提供了可视化和随机分析多维能量景观形状的工具，这些景观对应于发育和重新编程的表观遗传景观。我们证明CELLoGeNe在两个GRNs上管理诱导多能干细胞的不同方面，识别实验验证的吸引子并揭示潜在的重编程障碍。CELLoGeNe是一个通用的框架，可以应用于各种生物系统，提供细胞内动力学的广泛图片，否则无法与现有的方法。
Experimental and computational efforts are constantly made to elucidate mechanisms controlling cell fate decisions during development and reprogramming. One powerful computational method is to consider cell commitment and reprogramming as movements in an energy landscape. Here, we develop Computation of Energy Landscapes of Logical Gene Networks (CELLoGeNe), which maps Boolean implementation of gene regulatory networks (GRNs) into energy landscapes. CELLoGeNe removes inadvertent symmetries in the energy landscapes normally arising from standard Boolean operators. Furthermore, CELLoGeNe provides tools to visualize and stochastically analyze the shapes of multi-dimensional energy landscapes corresponding to epigenetic landscapes for development and reprogramming. We demonstrate CELLoGeNe on two GRNs governing different aspects of induced pluripotent stem cells, identifying experimentally validated attractors and revealing potential reprogramming roadblocks. CELLoGeNe is a general framework that can be applied to various biological systems offering a broad picture of intracellular dynamics otherwise inaccessible with existing methods.