论文标题

在微生物组的广义Lotka-Volterra模型中导航和控制结果

Navigation and control of outcomes in a generalized Lotka-Volterra model of the microbiome

论文作者

Jones, Eric W., Shankin-Clarke, Parker, Carlson, Jean M.

论文摘要

广义的Lotka-Volterra(GLV)方程将微生物组建模为相互作用的生态物种的集合。在这里,我们使用特定的实验衍生的艰难梭菌感染(CDI)的GLV模型作为案例研究,以生成适用于通用GLV模型的方法。我们研究了如何通过应用直接控制方案在多个稳态之间转变GLV系统,这些方案通过微生物物种的瞬时添加或减法来改变系统状态。然后,将点吸引子吸引人吸引力的几何形状压缩到一个吸引者网络中,该网络将多稳定的高维景观分解到Bistable子系统的网络中。该吸引子网络用于确定有效的(总干预量最小化)协议,该协议将系统从一个盆地驱动到另一个盆地。在某些情况下,最有效的控制协议是循环曲目,将通过具有顺序干预的中间稳态将系统带入系统。在临床上,微生物组的有效控制具有相关的细菌疗法应用,该应用程序试图通过直接改变肠道微生物组的组成来弥补微生物组相关疾病。

The generalized Lotka-Volterra (gLV) equations model the microbiome as a collection of interacting ecological species. Here we use a particular experimentally-derived gLV model of C. difficile infection (CDI) as a case study to generate methods that are applicable to generic gLV models. We examine how to transition gLV systems between multiple steady states through the application of direct control protocols, which alter the state of the system via the instantaneous addition or subtraction of microbial species. Then, the geometry of the basins of attraction of point attractors is compressed into an attractor network, which decomposes a multistable high-dimensional landscape into web of bistable subsystems. This attractor network is used to identify efficient (total intervention volume minimizing) protocols that drive the system from one basin to another. In some cases, the most efficient control protocol is circuitous and will take the system through intermediate steady states with sequential interventions. Clinically, the efficient control of the microbiome has pertinent applications for bacteriotherapies, which seek to remedy microbiome-affiliated diseases by directly altering the composition of the gut microbiome.

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