Cell-free DNA is generated in a highly specific biological process that yields a characteristic fragment length profile. Thus, we recommend preparing a library that does not change the size profile in any way: using the "Twist Mechanical Fragmentation Library Prep Kit" without any additional fragmentation treatment. Our library insert sizes look superb when we use that method. We have used Twist UMI adapters extensively on the cfDNA samples, and they work great for duplex consensus and getting good assessments of the mutation rates.