{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:38:32Z","timestamp":1773805112675,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009030","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000}}],"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["HR0011-17-2-0047"],"award-info":[{"award-number":["HR0011-17-2-0047"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["HR0011-17-2-0047"],"award-info":[{"award-number":["HR0011-17-2-0047"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["HR0011-17-2-0047"],"award-info":[{"award-number":["HR0011-17-2-0047"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["HR0011-17-2-0047"],"award-info":[{"award-number":["HR0011-17-2-0047"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["HR0011-17-2-0047"],"award-info":[{"award-number":["HR0011-17-2-0047"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008476","name":"University of California, Irvine","doi-asserted-by":"publisher","award":["UC Irvine Malaria Initiative"],"award-info":[{"award-number":["UC Irvine Malaria Initiative"]}],"id":[{"id":"10.13039\/100008476","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014220","name":"Innovative Genomics Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Interest in gene drive technology has continued to grow as promising new drive systems have been developed in the lab and discussions are moving towards implementing field trials. The prospect of field trials requires models that incorporate a significant degree of ecological detail, including parameters that change over time in response to environmental data such as temperature and rainfall, leading to seasonal patterns in mosquito population density. Epidemiological outcomes are also of growing importance, as: i) the suitability of a gene drive construct for release will depend on its expected impact on disease transmission, and ii) initial field trials are expected to have a measured entomological outcome and a modeled epidemiological outcome. We present MGDrivE 2 (Mosquito Gene Drive Explorer 2): a significant development from the MGDrivE 1 simulation framework that investigates the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations. Key strengths and fundamental improvements of the MGDrivE 2 framework are: i) the ability of parameters to vary with time and induce seasonal population dynamics, ii) an epidemiological module accommodating reciprocal pathogen transmission between humans and mosquitoes, and iii) an implementation framework based on stochastic Petri nets that enables efficient model formulation and flexible implementation. Example MGDrivE 2 simulations are presented to demonstrate the application of the framework to a CRISPR-based split gene drive system intended to drive a disease-refractory gene into a population in a confinable and reversible manner, incorporating time-varying temperature and rainfall data. The simulations also evaluate impact on human disease incidence and prevalence. Further documentation and use examples are provided in vignettes at the project\u2019s CRAN repository. MGDrivE 2 is freely available as an open-source R package on CRAN (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/cran.r-project.org\/package=MGDrivE2\" xlink:type=\"simple\">https:\/\/CRAN.R-project.org\/package=MGDrivE2<\/jats:ext-link>\n                    ). We intend the package to provide a flexible tool capable of modeling gene drive constructs as they move closer to field application and to infer their expected impact on disease transmission.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1009030","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T13:37:59Z","timestamp":1621604279000},"page":"e1009030","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["MGDrivE 2: A simulation framework for gene drive systems incorporating seasonality and epidemiological dynamics"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5781-9493","authenticated-orcid":true,"given":"Sean L.","family":"Wu","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4718-257X","authenticated-orcid":true,"given":"Jared B.","family":"Bennett","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7378-8853","authenticated-orcid":true,"given":"H\u00e9ctor M.","family":"S\u00e1nchez C.","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-7981","authenticated-orcid":true,"given":"Andrew J.","family":"Dolgert","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7633-677X","authenticated-orcid":true,"given":"Tom\u00e1s M.","family":"Le\u00f3n","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0603-7341","authenticated-orcid":true,"given":"John M.","family":"Marshall","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"pcbi.1009030.ref001","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/nbt.4245","article-title":"A CRISPR-Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes","volume":"36","author":"K Kyrou","year":"2018","journal-title":"Nat Biotechnol"},{"key":"pcbi.1009030.ref002","article-title":"Development of a confinable gene drive system in the human disease vector","volume":"9","author":"M Li","year":"2020","journal-title":"Elife"},{"key":"pcbi.1009030.ref003","doi-asserted-by":"crossref","first-page":"22805","DOI":"10.1073\/pnas.2010214117","article-title":"Next-generation gene drive for population modification of the malaria vector mosquito","volume":"117","author":"R Carballar-Lejaraz\u00fa","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi.1009030.ref004","doi-asserted-by":"crossref","article-title":"Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi","author":"A Adolfi","DOI":"10.1038\/s41467-020-19426-0"},{"key":"pcbi.1009030.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4269\/ajtmh.18-0083","article-title":"Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group \u2020","author":"S James","year":"2018","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"pcbi.1009030.ref006","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1089\/vbz.2019.2606","article-title":"Toward the Definition of Efficacy and Safety Criteria for Advancing Gene Drive-Modified Mosquitoes to Field Testing","volume":"20","author":"SL James","year":"2020","journal-title":"Vector Borne Zoonotic Dis"},{"key":"pcbi.1009030.ref007","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1111\/ele.13335","article-title":"Thermal biology of mosquito-borne disease","volume":"22","author":"EA Mordecai","year":"2019","journal-title":"Ecol Lett"},{"key":"pcbi.1009030.ref008","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/1756-3305-4-153","article-title":"Modelling the impact of vector control interventions on Anopheles gambiae population dynamics","volume":"4","author":"MT White","year":"2011","journal-title":"Parasit Vectors"},{"key":"pcbi.1009030.ref009","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/2041-210X.13318","article-title":"MGDrivE: A modular simulation framework for the spread of gene drives through spatially-explicit mosquito populations","volume":"11","author":"C. 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