Mixture detection with Demixtify

August E Woerner; Benjamin Crysup; Jonathan L King; Nicole M Novroski; Michael D Coble

doi:10.1016/j.fsigen.2023.102980

Mixture detection with Demixtify

Forensic Sci Int Genet. 2024 Mar:69:102980. doi: 10.1016/j.fsigen.2023.102980. Epub 2023 Nov 25.

Authors

August E Woerner¹, Benjamin Crysup², Jonathan L King³, Nicole M Novroski⁴, Michael D Coble²

Affiliations

¹ Center for Human Identification, University of North Texas Health Science Center, Fort Worth, TX, USA; Department of Microbiology, Immunology and Genetics, University of North Texas Health Science, Center, Fort Worth, TX, USA. Electronic address: august.woerner@unthsc.edu.
² Center for Human Identification, University of North Texas Health Science Center, Fort Worth, TX, USA; Department of Microbiology, Immunology and Genetics, University of North Texas Health Science, Center, Fort Worth, TX, USA.
³ Center for Human Identification, University of North Texas Health Science Center, Fort Worth, TX, USA.
⁴ Center for Human Identification, University of North Texas Health Science Center, Fort Worth, TX, USA; Department of Anthropology, University of Toronto, Mississauga, ON, Canada.

PMID: 38016331
DOI: 10.1016/j.fsigen.2023.102980

Abstract

The de facto genetic markers of forensics are short tandem repeats (STRs). There are many analytical tools designed to work with STRs, including techniques for analyzing and assessing DNA mixtures. In contrast, the nascent field of forensic genetic genealogy often relies on biallelic single nucleotide polymorphisms (SNPs). Tools designed for the forensic assessment of SNPs are somewhat lacking, especially for DNA mixtures. In this paper we introduce Demixtify, a program that detects DNA mixtures using biallelic SNPs. Demixtify is quite powerful; highly imbalanced mixtures can be detected (≤1:99, considering in silico and in vitro mixtures) when coverage is ample. Demixtify can also detect mixtures in low coverage (∼1×) samples (when the mixture is relatively balanced). Demixtify includes an empirical estimator of sequence error that is specific to the markers assayed, making it especially relevant to the forensic community. Orthogonal techniques are also developed to characterize in vitro mixtures, as well as samples thought to be single source, and the results of these approaches serve to validate the techniques presented.

Keywords: Activity level; DNA mixtures; Genetic genealogy; Mixture detection; Single nucleotide polymorphisms; Whole genome sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Fingerprinting*
DNA* / genetics
High-Throughput Nucleotide Sequencing
Humans
Microsatellite Repeats
Polymorphism, Single Nucleotide
Sequence Analysis, DNA / methods

Substances

DNA