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My super-quick skim of the paper shows that they are indeed using cfDNA. The novelty presented lies in the creation and application of a technique they dub "targeted error correction sequencing" (TEC-Seq).

Figure 2 shows the sequencing error rate reduced from around 1e-4 using conventional NGS to 1e-6 using TEC-Seq.

This increased sensitivity allows for discovery of early cancer at levels that are undetectable using existing cfDNA testing techniques.

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It's "funny" how they take all their high quality enzymatic reagents from the company NEB and do this error-repair step (which something NEB has claimed and shown that people should be doing with their NGS sample), and whole they use a high fidelity polymerase (Phusion), they don't use the highest fidelity (e.g. NEB Q5 or Kapa HIFI). Also, NEB makes a specific kit to repair NGS samples (i.e. Called pre-CR). Combined this would have translated into a 10-fold lower error rate (so regular NGS 10^-4, this paper 10^-6, then 10^-7 with even better enzymes).

Targeted capture using Agilent's SureSelect is pretty common in the cancer field. Their custom implementation allows for oversampling (30,000x) which, along the enzymatic error correction, allows them a high confidence in the target they chose to evaluate.

Overall, I think this is neat.

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