Ultima Genomics has developed a novel duplex sequencing method, paired-plus-minus sequencing (PPM-seq), boosting yield by approximately tenfold compared to existing techniques. The method achieves base substitution detection accuracy at one in a million (Q60 phred score) by analyzing both DNA strands, reducing errors from sample preparation and sequencing. Proof-of-concept studies led by Weill Cornell Medicine demonstrated PPM-seq's superior performance versus other state-of-the-art duplex methods like NanoSeq and CODEC. This increased yield can reduce oversequencing needs, enabling clinical whole-genome use in cancer diagnostics, including tumor-informed minimal residual disease testing, with promising implications for non-invasive liquid biopsy applications.