Time point measure for free#

Received: FebruAccepted: SeptemPublished: October 18, 2021Ĭopyright: © 2021 Cresta et al. (2021) Time to revisit the endpoint dilution assay and to replace the TCID 50 as a measure of a virus sample’s infection concentration.

Time point measure for free#

midSIN can be accessed for free on any device (laptop, cellular phone, tablet) from any web browser, without the need to download and install software.Ĭitation: Cresta D, Warren DC, Quirouette C, Smith AP, Lane LC, Smith AM, et al. Computing the SIN from one’s endpoint dilution assay outcome requires no change in experimental procedure, and can be done conveniently via a web-application we developed, called midSIN. It corresponds to the number of infections the virus sample will cause, which can be used directly to achieve the desired multiplicity of infection. We propose replacing the TCID 50 with a more accurate, robust, and biologically meaningful measurement unit we call Specific INfection (SIN). Unfortunately, the commonly used methods to estimate the TCID 50 from the assay’s outcome yield biased approximations that relate poorly to the number of infections the sample will cause. One approach, the endpoint dilution assay, aims to estimate the number of TCID 50 contained in a sample, where one TCID 50 is the dose at which a virus sample is expected to infect a tissue or cell culture 50% of the time, on average. The infectivity of a virus sample is measured by the infections it causes. We hope to see their universal adoption to measure the infectivity of virus samples. The simplicity of SIN as a measure and the greater accuracy provided by midSIN make them an easy and superior replacement for the TCID 50 and other in vitro culture ID 50 measures. The impact of endpoint dilution plate design choices (dilution factor, replicates per dilution) on measurement accuracy is also explored. midSIN’s estimates are shown to be more accurate and robust than the Reed-Muench and Spearman-Kärber approximations. It can therefore be used directly to achieve a desired multiplicity of infection, similarly to how plaque or focus forming units (PFU, FFU) are used. We analyzed influenza and respiratory syncytial virus samples using midSIN and demonstrated that the SIN/mL reliably corresponds to the number of infections a sample will cause per mL. midSIN computes a virus sample’s SIN concentration using Bayesian inference based on the results of a standard endpoint dilution assay, and requires no changes to current experimental protocols. We introduce a replacement for the ID 50 that we call Specific INfection (SIN) along with a free and open-source web-application, midSIN ( ) to calculate it. The endpoint dilution assay’s output, the 50% infectious dose (ID 50), is calculated using the Reed-Muench or Spearman-Kärber mathematical approximations, which are biased and often miscalculated.