Evidence map›Paper›PMID 34662338›Full record

ArticlePLoS computational biology2021

Time to revisit the endpoint dilution assay and to replace the TCID50 as a measure of a virus sample's infection concentration.

Daniel Cresta, Donald C Warren, Christian Quirouette, Amanda P Smith, Lindey C Lane, Amber M Smith, Catherine A A Beauchemin

Erratum issuedAbstract read
In one paragraph

Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Tracking Prions by RT-QuIC: An Update.Sub-cellular biochemistry · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Daniel CrestaDepartment of Physics, Ryerson University, Toronto, Ontario, Canada.ORCID 0000-0001-7524-9001
Donald C WarrenInterdisciplinary Theoretical and Mathematical Sciences (iTHEMS) program, RIKEN, Wako-shi, Saitama, Japan.ORCID 0000-0002-3222-9059
Christian QuirouetteDepartment of Physics, Ryerson University, Toronto, Ontario, Canada.ORCID 0000-0002-9461-6660
Amanda P SmithDepartment of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.ORCID 0000-0003-2428-1620
Lindey C LaneDepartment of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.ORCID 0000-0002-9600-0472
Amber M SmithDepartment of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.ORCID 0000-0002-7092-6904
Catherine A A BeaucheminDepartment of Physics, Ryerson University, Toronto, Ontario, Canada.ORCID 0000-0003-0599-0069

Funding

Predictive Modeling of Influenza-Pneumococcal CoinfectionR01AI139088 · NIAID · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI SMITH, AMBER M · 2018 to 2022
$2.1M
NIAID NIH HHS R01 AI139088
6 · The paper itself

Abstract

The endpoint dilution assay's output, the 50% infectious dose (ID50), is calculated using the Reed-Muench or Spearman-Kärber mathematical approximations, which are biased and often miscalculated. We introduce a replacement for the ID50 that we call Specific INfection (SIN) along with a free and open-source web-application, midSIN (https://midsin.physics.ryerson.ca) to calculate it. 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 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. 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. midSIN's estimates are shown to be more accurate and robust than the Reed-Muench and Spearman-Kärber approximations. The impact of endpoint dilution plate design choices (dilution factor, replicates per dilution) on measurement accuracy is also explored. The simplicity of SIN as a measure and the greater accuracy provided by midSIN make them an easy and superior replacement for the TCID50 and other in vitro culture ID50 measures. We hope to see their universal adoption to measure the infectivity of virus samples.

Indexed as

Bayes TheoremBiological AssayComputational BiologyViral Plaque AssayVirus Diseases

Identifiers

PMID34662338
PMCPMC8553042

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.