Olivar: towards automated variant aware primer design for multiplex tiled amplicon sequencing of pathogens

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dc.citation.articleNumber6306en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber15en_US
dc.contributor.authorWang, Michael X.en_US
dc.contributor.authorLou, Esther G.en_US
dc.contributor.authorSapoval, Nicolaeen_US
dc.contributor.authorKim, Eddieen_US
dc.contributor.authorKalvapalle, Prashanten_US
dc.contributor.authorKille, Bryceen_US
dc.contributor.authorElworth, R. A. Leoen_US
dc.contributor.authorLiu, Yunxien_US
dc.contributor.authorFu, Yileien_US
dc.contributor.authorStadler, Lauren B.en_US
dc.contributor.authorTreangen, Todd J.en_US
dc.date.accessioned2024-08-22T15:28:50Zen_US
dc.date.available2024-08-22T15:28:50Zen_US
dc.date.issued2024en_US
dc.description.abstractTiled amplicon sequencing has served as an essential tool for tracking the spread and evolution of pathogens. Over 15 million complete SARS-CoV-2 genomes are now publicly available, most sequenced and assembled via tiled amplicon sequencing. While computational tools for tiled amplicon design exist, they require downstream manual optimization both computationally and experimentally, which is slow and costly. Here we present Olivar, a first step towards a fully automated, variant-aware design of tiled amplicons for pathogen genomes. Olivar converts each nucleotide of the target genome into a numeric risk score, capturing undesired sequence features that should be avoided. In a direct comparison with PrimalScheme, we show that Olivar has fewer mismatches overlapping with primers and predicted PCR byproducts. We also compare Olivar head-to-head with ARTIC v4.1, the most widely used primer set for SARS-CoV-2 sequencing, and show Olivar yields similar read mapping rates (~90%) and better coverage to the manually designed ARTIC v4.1 amplicons. We also evaluate Olivar on real wastewater samples and found that Olivar has up to 3-fold higher mapping rates while retaining similar coverage. In summary, Olivar automates and accelerates the generation of tiled amplicons, even in situations of high mutation frequency and/or density. Olivar is available online as a web application at https://olivar.rice.edu and can be installed locally as a command line tool with Bioconda. Source code, installation guide, and usage are available at https://github.com/treangenlab/Olivar.en_US
dc.identifier.citationWang, M. X., Lou, E. G., Sapoval, N., Kim, E., Kalvapalle, P., Kille, B., Elworth, R. A. L., Liu, Y., Fu, Y., Stadler, L. B., & Treangen, T. J. (2024). Olivar: Towards automated variant aware primer design for multiplex tiled amplicon sequencing of pathogens. Nature Communications, 15(1), 6306. https://doi.org/10.1038/s41467-024-49957-9en_US
dc.identifier.digitals41467-024-49957-9en_US
dc.identifier.doihttps://doi.org/10.1038/s41467-024-49957-9en_US
dc.identifier.urihttps://hdl.handle.net/1911/117703en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleOlivar: towards automated variant aware primer design for multiplex tiled amplicon sequencing of pathogensen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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