MGDrivE: A modular simulation framework for the spread of gene drives through spatially explicit mosquito populations
MGDrivE: A modular simulation framework for the spread of gene drives through spatially explicit mosquito populations
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DOI：
10.1111/2041-210x.13318
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发表时间：
2019-11-05
影响因子：
6.6
通讯作者：
Marshall, John M.
中科院分区：
文献类型：
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作者：
Sanchez, Hector M. C.;Wu, Sean L.;Marshall, John M.
疟疾、登革热、寨卡病毒和其他蚊媒疾病继续在世界大部分地区构成重大的全球健康负担，尽管基于疟疾的工具和抗疟药物得到广泛分发。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，重新引发了人们对该技术应用于控制蚊子及其传播疾病的兴趣。这项技术的多功能性使得广泛的基因驱动架构得以实现，从而需要探索其种群水平和空间动态。我们提出了MGDrivE（蚊子基因驱动浏览器）：一个模拟框架，旨在研究各种基因驱动架构的种群动态及其通过空间显式蚊子种群的传播。MGDrivE框架的一个关键优势是其模块化：（a）遗传遗传模块适应显示用户定义的遗传模式的基因驱动系统的动态，（b）种群动态模块适应各种蚊子疾病媒介和昆虫农业害虫的生活史，以及（B）景观模块生成集合种群模型，通过该模型，昆虫种群通过空间迁移连接。呈现示例MGDrivE模拟以证明框架对基于CRISPR/Cas9的归巢基因驱动的应用，用于：（a）将疾病难治性基因驱动到群体中（即群体替换），以及（B）破坏女性生育力所需的基因（即群体抑制），在两种情况下并入归巢抗性等位基因。更多的文档和使用示例在项目的Github存储库中提供。MGDrivE是CRAN上免费提供的开源r包。我们打算包提供一个灵活的工具，能够模拟新的继承修改结构，因为他们提出并成为可用。基因驱动领域发展非常迅速，我们欢迎对未来发展提出建议。
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. 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. 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. 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.