Development and validation of open-source software for DNA mixture interpretation based on a quantitative continuous model

Abstract

In criminal investigations, forensic scientists need to evaluate DNA mixtures. The estimation of the number of contributors and evaluation of the contribution of a person of interest (POI) from these samples are challenging. In this study, we developed a new open-source software “Kongoh” for interpreting DNA mixture based on a quantitative continuous model. The model uses quantitative information of peak heights in the DNA profile and considers the effect of artifacts and allelic drop-out. By using this software, the likelihoods of 1–4 persons’ contributions are calculated, and the most optimal number of contributors is automatically determined; this differs from other open-source software. Therefore, we can eliminate the need to manually determine the number of contributors before the analysis. Kongoh also considers allele- or locus-specific effects of biological parameters based on the experimental data. We then validated Kongoh by calculating the likelihood ratio (LR) of a POI’s contribution in true contributors and non-contributors by using 2–4 person mixtures analyzed through a 15 short tandem repeat typing system. Most LR values obtained from Kongoh during true-contributor testing strongly supported the POI’s contribution even for small amounts or degraded DNA samples. Kongoh correctly rejected a false hypothesis in the non-contributor testing, generated reproducible LR values, and demonstrated higher accuracy of the estimated number of contributors than another software based on the quantitative continuous model. Therefore, Kongoh is useful in accurately interpreting DNA evidence like mixtures and small amounts or degraded DNA samples.

Internal validation of STRmix™ – A multi laboratory response to PCAST

“…These include the New York City Office of Chief Medical Examiner's FST Tool [3], TrueAllele® [4], and STRmix™ [5]. More recently the validation of GenoProof Mixture 3 [6] and Kongoh [7] has been reported.…”

Four model variants within a continuous forensic DNA mixture interpretation framework: Effects on evidential inference and reporting

“…It has also been demonstrated that factors such as PCR and the content of allele frequency databases have an impact on the variation in the LR computed using a continuous method [ 28 , 29 ]. Recent work has demonstrated that differences in output between semi-continuous and continuous systems result in clear differences in the LRs for some samples [ 10 , 30 , 31 ]. Despite these studies, comparisons between continuous probabilistic systems are not readily available in the literature, though some examples using small datasets do exist.…”

“…Despite these studies, comparisons between continuous probabilistic systems are not readily available in the literature, though some examples using small datasets do exist. For example, Morimoto et al [ 31 ] compare the continuous system Kongoh to another continuous system, EuroForMix, and demonstrate that for most high-template simple mixtures tested the LR outcomes were similar; however differences in LRs obtained from each model were obtained for more complex mixtures wherein the authors attributed the variation in outputs as “differences in the computational principle of estimating peak height variances”. Though reports of inter-model comparisons in the scientific literature do exist, sometimes resulting in the use of multiple softwares to test one item of evidence [ 30 ], the published work use limited datasets or do not replicate the runs; thus, in this work, and pursuant to PCAST’s recommendation to publish large-scale studies, we supplement the forensic and scientific literary record by examining the variability between results obtained from four variants of CEESIt [ 32 ], a tool that computes a continuous LR for a person of interest.…”

The Probabilistic Genotyping Software STRmix: Utility and Evidence for its Validity

“…The use of MCMC is not novel and has been used to solve many complex problems within chemistry, physics, biology, statistics, and computer science. The continuous model software Kongoh utilizes MLE. Other continuous solutions of which we are aware include LikeLTD‐ht , DNAmixtures , and EuroForMix .…”