{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:55:21Z","timestamp":1789613721464,"version":"build-2803163510"},"posted":{"date-parts":[[2025,3,5]]},"group-title":"Epidemiology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,5]]},"abstract":"<jats:p>Transmission reconstruction--the inference of who infects whom in disease outbreaks--offers critical insights into how pathogens spread and provides opportunities for targeted control measures. We developed JUNIPER (Joint Underlying Network Inference for Phylogenetic and Epidemiological Reconstructions), a highly-scalable pathogen outbreak reconstruction tool that incorporates intrahost variation, incomplete sampling, and algorithmic parallelization. Central to JUNIPER is a statistical model for within-host variant frequencies observed by next generation sequencing, which we validated on a dataset of over 160,000 deep-sequenced SARS-CoV-2 genomes. Combining this within-host variation model with population-level evolutionary and transmission models, we developed a method for inferring phylogenies and transmission trees simultaneously. We benchmarked JUNIPER on computer-generated and real outbreaks in which transmission links were known or epidemiologically confirmed. We demonstrated JUNIPER's real-world utility on two large-scale datasets: over 1,500 bovine H5N1 cases and over 13,000 human COVID-19 cases. Based on these analyses, we quantified the elevated H5N1 transmission rates in California and identified high-confidence transmission events, and demonstrated the efficacy of vaccination for reducing SARS-CoV-2 transmission. By overcoming computational and methodological limitations in existing outbreak reconstruction tools, JUNIPER provides a robust framework for studying pathogen spread at scale.<\/jats:p>","DOI":"10.1101\/2025.03.02.25323192","type":"posted-content","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T01:30:40Z","timestamp":1741224640000},"source":"Crossref","is-referenced-by-count":4,"title":["JUNIPER: Reconstructing Transmission Events from Next-Generation Sequencing Data at Scale"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2834-8191","authenticated-orcid":false,"given":"Ivan","family":"Specht","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4738-5318","authenticated-orcid":false,"given":"Gage K","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Brock-Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4163-706X","authenticated-orcid":false,"given":"Lydia A","family":"Krasilnikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2110-7475","authenticated-orcid":false,"given":"Brittany A","family":"Petros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0977-2886","authenticated-orcid":false,"given":"Jonathan E","family":"Pekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7906-6042","authenticated-orcid":false,"given":"Mark","family":"Schifferli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6414-5570","authenticated-orcid":false,"given":"Ben","family":"Fry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2589-7777","authenticated-orcid":false,"given":"Lawrence C","family":"Madoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7802-4721","authenticated-orcid":false,"given":"Meagan","family":"Burns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6699-3568","authenticated-orcid":false,"given":"Stephen","family":"Schaffner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7226-7781","authenticated-orcid":false,"given":"Daniel J","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0082-968X","authenticated-orcid":false,"given":"Bronwyn L","family":"MacInnis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4233-5899","authenticated-orcid":false,"given":"Al","family":"Ozonoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4619-8174","authenticated-orcid":false,"given":"Patrick","family":"Varilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5430-5457","authenticated-orcid":false,"given":"Michael D","family":"Mitzenmacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9843-1890","authenticated-orcid":false,"given":"Pardis C","family":"Sabeti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.03.02.25323192","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:29:45Z","timestamp":1768508985000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.03.02.25323192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1101\/2025.03.02.25323192","relation":{},"subject":[],"published":{"date-parts":[[2025,3,5]]},"subtype":"preprint"}}