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The growing use of circulating cell-free (cfDNA) necessitates accurate variant detection at less than 1% allele frequencies due to a low population of DNA of interest within total cfDNA. This level of detection is critical for a variety of cfDNA applications including detection of circulating tumor DNA (ctDNA), detection of graft-derived cfDNA (GcfDNA) within normal plasma as a marker of graft integrity after organ transplantation, and for noninvasive prenatal testing (NIPT) where fetal cfDNA is detected at low frequencies in maternal plasma. 

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