Mixture detection with Demixtify

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.