{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:43:45Z","timestamp":1784857425276,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01HG012473"],"award-info":[{"award-number":["R01HG012473"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM152242"],"award-info":[{"award-number":["R35GM152242"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM156957"],"award-info":[{"award-number":["R35GM156957"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01AI159402"],"award-info":[{"award-number":["P01AI159402"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["besjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Methods Ecol Evol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:list>\n                      <jats:list-item>\n                        <jats:p>Infectious disease dynamics result from the complex interplay of epidemiological, ecological and evolutionary (epi\u2010eco\u2010evo) processes. Accurately modelling these coupled processes is crucial for understanding pathogen spread and informing public health strategies. However, existing genomic epidemiology simulators typically assume conditional independence among these processes: generating transmission trees independently of pathogen evolution, and then superimposing neutral mutations onto fixed genealogies without ecological feedback. This simplification fails to capture how pathogen evolution dynamically reshapes epidemic trajectories.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>We introduce e3SIM, an open\u2010source, agent\u2010based, forward\u2010time simulator for macOS and Linux that explicitly integrates pathogen transmission dynamics, molecular evolution and environmental factors. e3SIM incorporates configurable compartmental models, user\u2010defined host contact networks, customizable pathogen genetic architectures and optional eco\u2010evolutionary features (e.g. within\u2010host dynamics, multi\u2010strain infections). This integration enables realistic modelling of pathogen spread and evolution. Key features include modularity, flexible epidemiological and population\u2010genetic modelling, time\u2010varying environmental factors and a user\u2010friendly graphical interface.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          We demonstrated e3SIM's capabilities by simulating SARS\u2010CoV\u20102 and\n                          <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                          outbreaks. e3SIM captured the emergence and spread of drug\u2010resistant variants under sequential treatments, highlighting how pathogen evolution and environmental variations dynamically reshape epidemic trajectories. We also illustrated how interactions between pathogen transmissibility and host population structures, particularly those involving socially active \u201csuperspreaders\u201d, strongly influence pathogen lineage expansion and transmission clusters. Runtime profiling demonstrated computational efficiency and scalability.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>e3SIM provides a powerful tool for simulating infectious disease dynamics through the explicit integration of epi\u2010eco\u2010evo processes, substantially enhancing realism and predictive accuracy in genomic epidemiology. Its modular, user\u2010friendly design supports broad applications across diverse host\u2010pathogen systems, enabling rigorous exploration of scenarios critical to public health.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>","DOI":"10.1111\/2041-210x.70278","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:23:00Z","timestamp":1772958180000},"page":"1051-1059","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["e3SIM: Epidemiological\u2010ecological\u2010evolutionary simulation framework for genomic epidemiology"],"prefix":"10.1111","volume":"17","author":[{"given":"Peiyu","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Molecular Biology &amp; Genetics Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenni","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Computer Science Cornell University  Ithaca New York USA"},{"name":"Tri\u2010Institutional Computational Biology &amp; Medicine PhD Program Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Computer Science Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Computer Science Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Tung \u2018Jack\u2019","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Computational Biology Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin C.","family":"Haller","sequence":"additional","affiliation":[{"name":"Department of Computational Biology Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Sobkowiak","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Disease Yale School of Public Health  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie H.","family":"Chitwood","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Disease Yale School of Public Health  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Colijn","sequence":"additional","affiliation":[{"name":"Department of Mathematics Simon Fraser University  Burnaby British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Disease Yale School of Public Health  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu Y.","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Medicine Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp W.","family":"Messer","sequence":"additional","affiliation":[{"name":"Department of Computational Biology Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin T.","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Statistics and Data Science Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology &amp; Genetics Cornell University  Ithaca New York USA"},{"name":"Department of Computational Biology Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-2004","authenticated-orcid":false,"given":"Jaehee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Computational Biology Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54967"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg964"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/sysbio\/syw054"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/17513758.2010.503376"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo0173"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/2041\u2010210X.14038"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/veac045"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090727"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tree.2021.04.013"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/1755\u20100998.12968"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/723601"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3130"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2021.02.008"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40656\u2010021\u201000457\u20109"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vez003"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201008564\u2010w"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/2041\u2010210X.13422"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879\u2010019\u20103870\u20101"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty921"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/oso\/9780198832140.001.0001"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1010409"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.76174"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.11.020"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879\u2010017\u20102699\u20108"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyae100"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1202\u2010569"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129745"},{"key":"e_1_2_9_29_1","unstructured":"Xu P. 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G. &Kim J.(2026).e3SIM software and demo files.Zenodo.https:\/\/doi.org\/10.5281\/zenodo.18489185"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/2041\u2010210X.12628"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(10)70264\u20104"}],"container-title":["Methods in Ecology and Evolution"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/besjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/2041-210x.70278","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/besjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/2041-210x.70278","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/besjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/2041-210x.70278","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:57:49Z","timestamp":1775451469000},"score":1,"resource":{"primary":{"URL":"https:\/\/besjournals.onlinelibrary.wiley.com\/doi\/10.1111\/2041-210x.70278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,5]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/2041-210x.70278"],"URL":"https:\/\/doi.org\/10.1111\/2041-210x.70278","archive":["Portico"],"relation":{},"ISSN":["2041-210X","2041-210X"],"issn-type":[{"value":"2041-210X","type":"print"},{"value":"2041-210X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,5]]},"assertion":[{"value":"2025-05-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}