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Title: Statistical interpretation of the Amerithrax “morph” assay results

In the Amerithrax investigation PCR–based “morph assays” were used to link the anthrax letters with the RMR–1029 flask at USAMRIID. Quantitative data reported for several of these assays are not consistent with Poisson sampling statistics, but instead exhibit “Taylor's Law” behavior where the variance greatly exceeds the mean. A plausible statistical model for this behavior can explain the large number of observed negative and “inconclusive” findings, and implies a high likelihood that a repository sample could contain a “morph” mutant at concentrations well above the nominal detection limit but nonetheless give a negative or inconclusive test result. A Bayesian framework relates the assay results to the probability that a sample actually contains all four morph mutants, even though it tested negative for at least one. The analysis implies that the observed false negative rate actually does not significantly weaken the conclusion that the morph assays correctly excluded all but the stocks derived from RMR–1029 as possible sources of the letter powders, at least when the test results were unambiguous. In conclusion, these findings expand upon and resolve some of the issues cited in recent reviews, and indicate the importance of developing a rigorous statistical framework for interpreting “morph” assay data.
Authors:
ORCiD logo [1] ;  [1] ;  [2] ;  [2]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  2. United States Government Accountability Office, Washington, D.C. (United States)
Publication Date:
Report Number(s):
LLNL-JRNL-695537
Journal ID: ISSN 0173-0835; 825109
Grant/Contract Number:
AC52-07NA27344
Type:
Accepted Manuscript
Journal Name:
Electrophoresis (Weinheim)
Additional Journal Information:
Journal Name: Electrophoresis (Weinheim); Journal Volume: 39; Journal Issue: 2; Journal ID: ISSN 0173-0835
Publisher:
Wiley
Research Org:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org:
USDOE National Nuclear Security Administration (NNSA)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Amerithrax; Anthrax letters; Morphotype; RMR‐1029; Taylor's Law
OSTI Identifier:
1474341

Velsko, Stephan Paul, Osburn, Joanne J., Sharma, Sushil K., and Ashley, James D.. Statistical interpretation of the Amerithrax “morph” assay results. United States: N. p., Web. doi:10.1002/elps.201600287.
Velsko, Stephan Paul, Osburn, Joanne J., Sharma, Sushil K., & Ashley, James D.. Statistical interpretation of the Amerithrax “morph” assay results. United States. doi:10.1002/elps.201600287.
Velsko, Stephan Paul, Osburn, Joanne J., Sharma, Sushil K., and Ashley, James D.. 2017. "Statistical interpretation of the Amerithrax “morph” assay results". United States. doi:10.1002/elps.201600287. https://www.osti.gov/servlets/purl/1474341.
@article{osti_1474341,
title = {Statistical interpretation of the Amerithrax “morph” assay results},
author = {Velsko, Stephan Paul and Osburn, Joanne J. and Sharma, Sushil K. and Ashley, James D.},
abstractNote = {In the Amerithrax investigation PCR–based “morph assays” were used to link the anthrax letters with the RMR–1029 flask at USAMRIID. Quantitative data reported for several of these assays are not consistent with Poisson sampling statistics, but instead exhibit “Taylor's Law” behavior where the variance greatly exceeds the mean. A plausible statistical model for this behavior can explain the large number of observed negative and “inconclusive” findings, and implies a high likelihood that a repository sample could contain a “morph” mutant at concentrations well above the nominal detection limit but nonetheless give a negative or inconclusive test result. A Bayesian framework relates the assay results to the probability that a sample actually contains all four morph mutants, even though it tested negative for at least one. The analysis implies that the observed false negative rate actually does not significantly weaken the conclusion that the morph assays correctly excluded all but the stocks derived from RMR–1029 as possible sources of the letter powders, at least when the test results were unambiguous. In conclusion, these findings expand upon and resolve some of the issues cited in recent reviews, and indicate the importance of developing a rigorous statistical framework for interpreting “morph” assay data.},
doi = {10.1002/elps.201600287},
journal = {Electrophoresis (Weinheim)},
number = 2,
volume = 39,
place = {United States},
year = {2017},
month = {10}
}