Improving the Utilization of STRmix™ Variance Parameters as Semi-Quantitative Profile Modeling Metrics

Distributions of the variance parameter values developed during the validation process. Comparisons of these prior distributions to the run-specific average are one measure used by analysts to assess the reliability of a STRmix deconvolution. This study examined the behavior of three different STRmix variance parameters under standard amplification and interpretation conditions, as well as under a variety of challenging conditions, with the goal of making comparisons to the prior distributions more practical and meaningful. Using information found in STRmix v2.8 Interpretation Reports, we plotted the log10 of each variance parameter against the log10 of the template amount of the highest-level contributor (Tc) for a large set of mixture data amplified under standard conditions. We observed nonlinear trends in these plots, which we regressed to fourth-order polynomials, and used the regression data to establish typical ranges for the variance parameters over the Tc range. We then compared the typical variance parameter ranges to log10(variance parameter) v log10(Tc) plots for mixtures amplified and interpreted under a variety of challenging conditions. We observed several distinct patterns to variance parameter shifts in the challenged data interpretations in comparison to the unchallenged data interpretations, as well as distinct shifts in the unchallenged variance parameters away from their prior gamma distribution modes over specific ranges of Tc. These findings suggest that employing empirically determined working ranges for variance parameters may be an improved means of detecting whether aberrations in the interpretation were meaningful enough to trigger greater scrutiny of the electropherogram and genotype interpretation.