A molecular framework for enhancing quality control and sample integrity in forensic genome sequencing

DNA typing is essential for identifying crime scene evidence and missing and unknown persons. Molecular tags historically have been incorporated into DNA typing reactions to improve result interpretation. Molecular tags like barcodes and unique identifiers are integral to MPS, aiding in sample tracking and error detection. However, these tags do not fully leverage sequence variation to enhance quality control. To address this need, molecular etches, which are synthetic oligonucleotides that serve as an internal molecular information management system, are introduced. Molecular etches encode detailed sample information improving sample workflow history, tracking, contamination detection, and authenticity verification. Validation studies demonstrate the robustness of molecular etches in genomic sequencing, making them a valuable quality tool for forensic DNA analysis. •Molecular etches are introduced as a novel internal molecular information system.•Molecular etches were validated for robust, real-time sample tracking in MPS.•Molecular etches can detect contamination that was introduced with trace sample spikes.•Molecular etches are simple and cost-effective to implement in forensic labs.•Molecular etches enhance quality control and reduce sample error.