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MGDrivE: A modular simulation framework for the spread of gene drives through spatially explicit mosquito populations
Methods in Ecology and Evolution ( IF 6.3 ) Pub Date : 2019-11-05 , DOI: 10.1111/2041-210x.13318
Héctor M. Sánchez C. 1 , Sean L. Wu 1 , Jared B. Bennett 2 , John M. Marshall 1, 3
Affiliation  

  1. Malaria, dengue, Zika and other mosquito‐borne diseases continue to pose a major global health burden through much of the world, despite the widespread distribution of insecticide‐based tools and antimalarial drugs. The advent of CRISPR/Cas9‐based gene editing and its demonstrated ability to streamline the development of gene drive systems has reignited interest in the application of this technology to the control of mosquitoes and the diseases they transmit. The versatility of this technology has enabled a wide range of gene drive architectures to be realized, creating a need for their population‐level and spatial dynamics to be explored.
  2. We present MGDrivE (Mosquito Gene Drive Explorer): a simulation framework designed to investigate the population dynamics of a variety of gene drive architectures and their spread through spatially explicit mosquito populations. A key strength of the MGDrivE framework is its modularity: (a) a genetic inheritance module accommodates the dynamics of gene drive systems displaying user‐defined inheritance patterns, (b) a population dynamic module accommodates the life history of a variety of mosquito disease vectors and insect agricultural pests, and (c) a landscape module generates the metapopulation model by which insect populations are connected via migration over space.
  3. Example MGDrivE simulations are presented to demonstrate the application of the framework to CRISPR/Cas9‐based homing gene drive for: (a) driving a disease‐refractory gene into a population (i.e. population replacement), and (b) disrupting a gene required for female fertility (i.e. population suppression), incorporating homing‐resistant alleles in both cases. Further documentation and use examples are provided at the project's Github repository.
  4. MGDrivE is an open‐source r package freely available on CRAN. We intend the package to provide a flexible tool capable of modelling novel inheritance‐modifying constructs as they are proposed and become available. The field of gene drive is moving very quickly, and we welcome suggestions for future development.


中文翻译:

MGDrivE:一个模块化的模拟框架,用于通过空间明确的蚊子种群传播基因驱动力

  1. 尽管基于杀虫剂的工具和抗疟疾药物分布广泛,但疟疾,登革热,寨卡病毒和其他蚊媒疾病仍在全球大部分地区构成主要的全球健康负担。基于CRISPR / Cas9的基因编辑技术的出现及其简化基因驱动系统开发的能力,再次激发了人们对该技术在控制蚊子及其传播疾病中的应用的兴趣。该技术的多功能性使人们能够实现广泛的基因驱动架构,从而需要探索其种群水平和空间动态。
  2. 我们介绍了MGD riv E(蚊子基因驱动器浏览器):一种模拟框架,旨在调查各种基因驱动器结构的种群动态以及它们在空间上明确的蚊子种群中的传播。MGD riv E框架的主要优势在于其模块化:(a)遗传继承模块适应显示用户定义遗传模式的基因驱动系统的动态变化;(b)种群动态模块适应各种蚊虫的生活史病媒和昆虫农业害虫,以及(c)景观模块生成元种群模型,通过该模型,昆虫种群通过在空间上的迁移而相互连接。
  3. 展示了示例MGD riv E仿真以证明该框架在基于CRISPR / Cas9的归巢基因驱动中的应用:(a)将疾病难治性基因驱动到种群中(即种群替代),以及(b)破坏基因女性生育力(即抑制种群)所需的信息,在两种情况下均包含抗归巢的等位基因。该项目的Github存储库中提供了更多文档和使用示例。
  4. MGD riv E是CRAN上免费提供的开源r软件包。我们希望该软件包提供一个灵活的工具,能够对提出和可用的新颖的继承修改结构进行建模。基因驱动领域发展非常迅速,我们欢迎对未来发展的建议。
更新日期:2019-11-05
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