Mitchell Rebecca, Peck Michelle, Gorden Erin, Just Rebecca
National Bioforensic Analysis Center, National Biodefense Analysis and Countermeasures Center, Operated by Battelle National Biodefense Institute for the US. Department of Homeland Security Science and Technology Directorate, 8300 Research Plaza, Fort Detrick, MD 21702, USA.
Signature Science LLC, 1670 Discovery Drive, Charlottesville, VA 22911, USA.
Forensic Sci Int Genet. 2025 Mar;76:103224. doi: 10.1016/j.fsigen.2025.103224. Epub 2025 Jan 20.
The generation of forensic DNA profiles consisting of single nucleotide polymorphisms (SNPs) is now being facilitated by wider adoption of next-generation sequencing (NGS) methods in casework laboratories. At the same time, and in part because of this advance, there is an intense focus on the generation of SNP profiles from evidentiary specimens for so-called forensic or investigative genetic genealogy (FGG or IGG) applications. However, FGG methods are constrained by the algorithms for genealogical database searches, which were designed for use with single-source profiles, and the fact that many forensic samples are mixtures. To enable the use of two-person mixtures for FGG, we developed a workflow, MixDeR, for the deconvolution of mixed SNP profiles. MixDeR, a flexible and easy to use R package and Shiny app, processes ForenSeq Kintelligence® (QIAGEN, Inc.) SNP genotyping results and directs deconvolution of the profiles in EuroForMix (EFM). MixDeR then filters the EFM outputs to produce inferred single-source genotypes in reports formatted for use with GEDmatch® PRO. An optional MixDeR output includes metrics that assist with testing and validation of the workflow. As the Shiny app provides a graphical user interface and the software is designed to be run offline, MixDeR should be suitable for use by any laboratory developing FGG capabilities, no matter their bioinformatic resources or expertise.
下一代测序（NGS）方法在法医实验室中的广泛应用，推动了由单核苷酸多态性（SNP）构成的法医DNA图谱的生成。与此同时，部分由于这一进展，人们强烈关注从证据样本中生成SNP图谱，用于所谓的法医或调查遗传系谱（FGG或IGG）应用。然而，FGG方法受到系谱数据库搜索算法的限制，这些算法是为单源图谱设计的，而且许多法医样本是混合物。为了能够将两人混合样本用于FGG，我们开发了一种工作流程MixDeR，用于对混合SNP图谱进行解卷积。MixDeR是一个灵活且易于使用的R包和Shiny应用程序，它处理ForenSeq Kintelligence®（QIAGEN公司）SNP基因分型结果，并指导在EuroForMix（EFM）中对图谱进行解卷积。然后，MixDeR对EFM输出进行筛选，以生成格式适合与GEDmatch® PRO一起使用的报告中的推断单源基因型。MixDeR的一个可选输出包括有助于工作流程测试和验证的指标。由于Shiny应用程序提供了图形用户界面，并且该软件设计为可离线运行，MixDeR应该适合任何开发FGG能力的实验室使用，无论其生物信息资源或专业知识如何。
