Table 1.
Fragmentomic features of cfDNA in cancer.
| cfDNA Fragment Feature | Method | Analyte | Control Cohort | Cancer Entity Tested | Result | Reference |
|---|---|---|---|---|---|---|
| Fragment length shortening | WGS | Plasma | Healthy controls (n = 32), HBV (n = 67), liver cirrhosis (n = 36) |
HCC (n = 90) | Short cfDNA fragments preferentially carry tumor-associated CNVs | [42] |
| Fragment length shortening | sWGS | CSF | n/a | Glioma (n = 13) | Detectable CNVs in CSF correlates with higher abundance of short (<145 bp) cfDNA fragments | [51] |
| Fragment length shortening | tNGS; ddPCR |
Plasma | n/a | Melanoma (n = 8), CRC (n = 3), and pancreatic (n = 2) cancer | 2-fold enrichment of SNVs in short (<142 bp) cfDNA fragments |
[38] |
| Fragment length shortening | sWGS; tNGS |
Plasma | n/a | High-grade serous ovarian cancer (n = 13) |
Up to 11-fold enrichment of the mutated cfDNA fraction in short fragments (90 to 150 bp) | [49] |
| Multiple fragment size features | sWGS; tNGS |
Plasma | Healthy controls (n = 144) | Multiple cancerentities (n = 200) |
Enhanced CNV/SNV detection by short fragments; fragmentation feature-based cancer classification (AUC = 0.99) |
[41] |
| Position-specific fragment length variations | WGS | Plasma | Healthy controls (n = 245) | Multiple cancer entities (n = 236) |
Cancer detection based on genome-wide cfDNA fragmentation profiles (AUC = 0.94) |
[37] |
| Preferred end coordinates | WGS | Plasma | Healthy controls (n = 32), HBV (n = 67), liver cirrhosis (n = 36) |
HCC (n = 90) | Cancer classification based on fragments at tumor-associated preferred end coordinates (AUC = 0.88) | [56] |
| Fragment end motifs | WGS | Plasma | Healthy controls (n = 38), HBV (n = 17) |
HCC (n = 34) | Increased fragment end motif diversity in patients compared with controls | [67] |
| Jagged ends | WGBS | Plasma | Healthy controls (n = 8), HBV (n = 17) |
HCC (n = 34) | Cancer classification based on the increased jaggedness in cancer patients | [60] |
| Jagged ends | WGBS | Urine | Healthy controls (n = 39) | Bladder cancer (n = 43) |
Cancer classification based on the decreased jaggedness in cancer patients | [61] |
AUC, area under the curve; CNV, copy number variation; CRC, colorectal cancer; CSF, cerebrospinal fluid; ddPCR, digital droplet PCR; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; sWGS, shallow whole genome sequencing; tNGS, targeted next-generation sequencing; WGB, whole genome bisulfite sequencing; WGS, whole genome sequencing.