Sajid Noor, Convertino Laura, Friston Karl
Wellcome Centre for Human Neuroimaging, Institute of Neurology, University College London, London WC1N 3BG, UK.
Institute of Cognitive Neuroscience, University College London, London WC1N 3BG, UK.
Entropy (Basel). 2021 May 14;23(5):609. doi: 10.3390/e23050609.
Biological forms depend on a progressive specialization of pluripotent stem cells. The differentiation of these cells in their spatial and functional environment defines the organism itself; however, cellular mutations may disrupt the mutual balance between a cell and its niche, where cell proliferation and specialization are released from their autopoietic homeostasis. This induces the construction of cancer niches and maintains their survival. In this paper, we characterise cancer niche construction as a direct consequence of interactions between clusters of cancer and healthy cells. Explicitly, we evaluate these higher-order interactions between niches of cancer and healthy cells using Kikuchi approximations to the free energy. Kikuchi's free energy is measured in terms of changes to the sum of energies of baseline clusters of cells (or nodes) minus the energies of overcounted cluster intersections (and interactions of interactions, etc.). We posit that these changes in energy node clusters correspond to a long-term reduction in the complexity of the system conducive to cancer niche survival. We validate this formulation through numerical simulations of apoptosis, local cancer growth, and metastasis, and highlight its implications for a computational understanding of the etiopathology of cancer.
生物形态依赖于多能干细胞的逐步特化。这些细胞在其空间和功能环境中的分化定义了生物体本身；然而，细胞突变可能会破坏细胞与其生态位之间的相互平衡，在这种平衡中，细胞增殖和特化从其自我生成的稳态中释放出来。这会诱导癌症生态位的构建并维持其存活。在本文中，我们将癌症生态位构建描述为癌症细胞簇与健康细胞之间相互作用的直接结果。具体而言，我们使用对自由能的菊池近似来评估癌症和健康细胞生态位之间的这些高阶相互作用。菊池自由能是根据细胞（或节点）基线簇的能量总和的变化减去过度计数的簇交集（以及相互作用的相互作用等）的能量来衡量的。我们假定这些能量节点簇的变化对应于有利于癌症生态位存活的系统复杂性的长期降低。我们通过细胞凋亡、局部癌症生长和转移的数值模拟验证了这一公式，并强调了其对癌症病因病理学计算理解的意义。
