Table 1

Current cell-free DNA-based approaches for the detection of cancer

Approach	Methodology	Relative abundance of target signals	Assay	Number of targets	Performance	Cohort size	Tumor informed	Extent of clinical evaluation	Relative cost of approach	References
Mutation analysis	Capture-based targeted, multiplex PCR, genome-wide or whole-exome next generation sequencing	Few to hundreds of known mutations or genome-wide	Elio Plasma Resolve	33	VAF≥95% LoD 0.1%–0.5%	n=75	No	Clinical validity, case–control, prospective cohort	$$$–$$$$	32
			FoundationOne Liquid	324	VAF≥95% LoD 0.4%	n>30 cancer types	No			12
			Guardant360	74	VAF>80% LoD 0.25%	n>1500	No			34
			MRDetect	Genome-wide	VAF LoD 10⁻⁵, >85% at 20×, >99% at 50×	n=98	Yes			73
			Signatera	16	VAF>95% LoD 0.01%	n=49	Yes			35 36
			CancerSeek (DETECT-A)	16	Specificity: 98.9% Sensitivity: 27%	n=9,911	No			26
			RaDaR	48	VAF=95% LoD 0.001%	n=88, n=17	Yes			37 38
DNA methylation profiling	Bisulfite conversion- sequencing or DNA methylation immunoprecipitation-sequencing	Thousands to tens of thousands of CpG methylation differences	Galleri (PATHFINDER)	Targeted methylation	Specificity: 99.1% Sensitivity: 29%	n=6,621	No	Clinical validity, case–control, prospective cohort	$$$–$$$$	81
DNA methylation profiling			cfMeDIP-seq	Anti-5mc	Lung AUC: 0.971 AML AUC: 0.98 PDAC AUC: 0.92	n=388	No	Clinical validity, case–control, prospective cohort	$$$–$$$$	24 59
Fragmentation profiling	Low-coverage whole-genome, next-generation sequencing	Millions of fragmentation differences	DELFI	Genome-wide	AUC: 0.86 - 0.98 across cancer types	n=423	No	Proof-of-concept, clinical validity, case–control, prospective-retrospective cohort	$–$$	61–63
			End Motifs	Motif diversity score	AUC 0.86	n=89	No			70
			GALYFRE	Genome-wide	Specificity: 95% Sensitivity: 66.9%	n=661	No			71
		Mutational signatures	GEMINI	Genome-wide	AUC 0.90	n=109	No			41
		Mutational signatures	Pointy	Genome-wide	AUC 0.96	n=405	No			42

AML, acute myeloid leukemia; AUC, area under the curve; LoD, limit of detection; PDAC, pancreatic ductal adenocarcinoma; VAF, variant allele fraction.