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dc.contributor.authorMahmutovic, Anel
dc.contributor.authorGillman, Aaron Nicholas
dc.contributor.authorLauksund, Silje
dc.contributor.authorRobson Moe, Natasha-Anne
dc.contributor.authorManzi, Aimé
dc.contributor.authorStorflor, Merete
dc.contributor.authorAbel-Zur Wiesch Genannt Hülsho, Pia Karoline
dc.contributor.authorAbel, Sören
dc.date.accessioned2022-01-31T12:15:45Z
dc.date.available2022-01-31T12:15:45Z
dc.date.issued2021-01-19
dc.description.abstractMicrobial division rates determine the speed of mutation accumulation and thus the emergence of antimicrobial resistance. Microbial death rates are affected by antibiotic action and the immune system. Therefore, measuring these rates has advanced our understanding of host-pathogen interactions and antibiotic action. Several methods based on marker-loss or few inheritable neutral markers exist that allow estimating microbial division and death rates, each of which has advantages and limitations. Technical bottlenecks, i.e., experimental sampling events, during the experiment can distort the rate estimates and are typically unaccounted for or require additional calibration experiments.<p> <p>In this work, we introduce RESTAMP (Rate Estimates by Sequence Tag Analysis of Microbial Populations) as a method for determining bacterial division and death rates. This method uses hundreds of fitness neutral sequence barcodes to measure the rates and account for experimental bottlenecks at the same time. We experimentally validate RESTAMP and compare it to established plasmid loss methods.<p> <p>We find that RESTAMP has a number of advantages over plasmid loss or previous marker based techniques. (i) It enables to correct the distortion of rate estimates by technical bottlenecks. (ii) Rate estimates are independent of the sequence tag distribution in the starting culture allowing the use of an arbitrary number of tags. (iii) It introduces a bottleneck sensitivity measure that can be used to maximize the accuracy of the experiment.<p> <p>RESTAMP allows studying microbial population dynamics with great resolution over a wide dynamic range and can thus advance our understanding of host-pathogen interactions or the mechanisms of antibiotic action.en_US
dc.identifier.citationMahmutovic, Gillman, Lauksund, Robson Moe, Manzi, Storflor, Abel-Zur Wiesch Genannt Hülsho, Abel. RESTAMP – Rate estimates by sequence-tag analysis of microbial populations. Computational and Structural Biotechnology Journal. 2021en_US
dc.identifier.cristinIDFRIDAID 1922481
dc.identifier.doi10.1016/j.csbj.2021.01.017
dc.identifier.issn2001-0370
dc.identifier.urihttps://hdl.handle.net/10037/23846
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalComputational and Structural Biotechnology Journal
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.titleRESTAMP – Rate estimates by sequence-tag analysis of microbial populationsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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