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利用监督机器学习框架对 CRISPR 基因驱动器进行建模,以抑制入侵性啮齿动物。

Modeling CRISPR gene drives for suppression of invasive rodents using a supervised machine learning framework.

机构信息

Department of Computational Biology, Cornell University, Ithaca, New York, United States of America.

Manaaki Whenua-Landcare Research, Lincoln, New Zealand and School of Biological Sciences, University of Aberdeen, Aberdeen, United Kingdom.

出版信息

PLoS Comput Biol. 2021 Dec 29;17(12):e1009660. doi: 10.1371/journal.pcbi.1009660. eCollection 2021 Dec.

DOI:10.1371/journal.pcbi.1009660
PMID:34965253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8716047/
Abstract

Invasive rodent populations pose a threat to biodiversity across the globe. When confronted with these invaders, native species that evolved independently are often defenseless. CRISPR gene drive systems could provide a solution to this problem by spreading transgenes among invaders that induce population collapse, and could be deployed even where traditional control methods are impractical or prohibitively expensive. Here, we develop a high-fidelity model of an island population of invasive rodents that includes three types of suppression gene drive systems. The individual-based model is spatially explicit, allows for overlapping generations and a fluctuating population size, and includes variables for drive fitness, efficiency, resistance allele formation rate, as well as a variety of ecological parameters. The computational burden of evaluating a model with such a high number of parameters presents a substantial barrier to a comprehensive understanding of its outcome space. We therefore accompany our population model with a meta-model that utilizes supervised machine learning to approximate the outcome space of the underlying model with a high degree of accuracy. This enables us to conduct an exhaustive inquiry of the population model, including variance-based sensitivity analyses using tens of millions of evaluations. Our results suggest that sufficiently capable gene drive systems have the potential to eliminate island populations of rodents under a wide range of demographic assumptions, though only if resistance can be kept to a minimal level. This study highlights the power of supervised machine learning to identify the key parameters and processes that determine the population dynamics of a complex evolutionary system.

摘要

入侵的啮齿动物种群对全球的生物多样性构成威胁。当面临这些入侵者时,那些独立进化的本地物种往往是毫无防备的。CRISPR 基因驱动系统可以通过在入侵者中传播诱导种群崩溃的转基因来解决这个问题,并且即使在传统的控制方法不切实际或过于昂贵的情况下,也可以部署这些系统。在这里,我们开发了一个具有高精度的入侵啮齿动物岛屿种群的模型,该模型包含三种类型的抑制基因驱动系统。基于个体的模型具有空间明确性,允许世代重叠和种群规模波动,并且包括驱动适应性、效率、抗性等位基因形成率以及各种生态参数的变量。评估具有如此多参数的模型的计算负担对全面理解其结果空间构成了实质性的障碍。因此,我们在种群模型中配备了一个元模型,该模型利用有监督的机器学习以高度的准确性来近似基础模型的结果空间。这使我们能够对种群模型进行详尽的研究,包括使用数千万次评估进行基于方差的敏感性分析。我们的结果表明,只要能够将抗性保持在最低水平,具有足够能力的基因驱动系统有可能在广泛的人口假设下消除岛屿上的啮齿动物种群。这项研究强调了监督机器学习在确定复杂进化系统的种群动态的关键参数和过程方面的强大功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/5acc6ca76e3d/pcbi.1009660.g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/a18b92849501/pcbi.1009660.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/6ef0cb076bc6/pcbi.1009660.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/886bc920dd3b/pcbi.1009660.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/03bd2ca89a29/pcbi.1009660.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/87f4143b715f/pcbi.1009660.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/c4d9e432664b/pcbi.1009660.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/aafb7489534c/pcbi.1009660.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/d3e788aa4d81/pcbi.1009660.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/5334e143a9c6/pcbi.1009660.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/d6df8ee62499/pcbi.1009660.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/a3d879d6ff86/pcbi.1009660.g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/f92ecd0ce6a8/pcbi.1009660.g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/a99be88646eb/pcbi.1009660.g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/5acc6ca76e3d/pcbi.1009660.g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/a18b92849501/pcbi.1009660.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/6ef0cb076bc6/pcbi.1009660.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/886bc920dd3b/pcbi.1009660.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/03bd2ca89a29/pcbi.1009660.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/87f4143b715f/pcbi.1009660.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/c4d9e432664b/pcbi.1009660.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/aafb7489534c/pcbi.1009660.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/d3e788aa4d81/pcbi.1009660.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/5334e143a9c6/pcbi.1009660.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/d6df8ee62499/pcbi.1009660.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/a3d879d6ff86/pcbi.1009660.g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/f92ecd0ce6a8/pcbi.1009660.g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/a99be88646eb/pcbi.1009660.g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35a9/8716047/5acc6ca76e3d/pcbi.1009660.g014.jpg

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Suppression gene drive in continuous space can result in unstable persistence of both drive and wild-type alleles.
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