Source 1primary paper2024International Journal of Molecular Sciences
Toolkit/cfDNA fragmentomics evaluation
cfDNA fragmentomics evaluation
Also known as: cfDNA fragmentomics
Taxonomy: Technique Branch / Method. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
cfDNA fragmentomics evaluation is an assay method that analyzes plasma cell-free DNA fragment length distributions and fragment end motifs to identify signatures associated with active gene expression. In a 2024 study, integrating short-fragment frequency with end-motif information improved enrichment for highly expressed genes in plasma samples from lung cancer patients and healthy individuals.
Usefulness & Problems
Why this is useful
This method is useful for extracting gene expression-associated information from liquid biopsy cfDNA without direct tissue sampling. The cited study indicates that combining fragment size and end-motif features can improve identification of highly expressed genes relative to using fragment length information alone.
Problem solved
This assay addresses the problem of inferring active gene expression states from plasma-derived cfDNA. Specifically, it helps distinguish genes with high expression by leveraging enrichment of short cfDNA fragments and distinct fragment end motifs.
Problem links
Need better screening or enrichment leverage
DerivedcfDNA fragmentomics evaluation is an assay method that analyzes plasma cell-free DNA fragment lengths and fragment end motifs to identify features associated with active gene expression. In the cited 2024 study, it was applied to plasma from lung cancer patients (n = 12) and healthy individuals (n = 7), and integration of short-fragment frequency with end-motif information improved enrichment for highly expressed genes.
Taxonomy & Function
Primary hierarchy
Technique Branch
Method: A concrete measurement method used to characterize an engineered system.
Mechanisms
fragment end motif-based enrichmentfragment end motif-based enrichmentmultifeature integration of fragment length and end motifsmultifeature integration of fragment length and end motifssize-based selection enrichmentsize-based selection enrichmentTechniques
Functional AssayFunctional AssayFunctional AssaySelection / EnrichmentSelection / EnrichmentSelection / EnrichmentTarget processes
selectionImplementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: sensor
The method was performed on plasma cell-free DNA from human subjects, including lung cancer patients and healthy individuals. The evidence supports analysis of fragment lengths and fragment end motifs, but does not provide detailed protocols for library preparation, sequencing platform, computational pipeline, or thresholding criteria.
The available evidence is limited to a single 2024 study with a small cohort and association-based claims. The supplied evidence does not report analytical sensitivity, specificity, reproducibility, sequencing requirements, or validation across additional diseases, cohorts, or laboratories.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Distinct GC-rich fragment end motifs are enriched after cfChIP.
Furthermore, distinct GC-rich FEMs were enriched after cfChIP.
Distinct GC-rich fragment end motifs are enriched after cfChIP.
Furthermore, distinct GC-rich FEMs were enriched after cfChIP.
Distinct GC-rich fragment end motifs are enriched after cfChIP.
Furthermore, distinct GC-rich FEMs were enriched after cfChIP.
Distinct GC-rich fragment end motifs are enriched after cfChIP.
Furthermore, distinct GC-rich FEMs were enriched after cfChIP.
Distinct GC-rich fragment end motifs are enriched after cfChIP.
Furthermore, distinct GC-rich FEMs were enriched after cfChIP.
Distinct GC-rich fragment end motifs are enriched after cfChIP.
Furthermore, distinct GC-rich FEMs were enriched after cfChIP.
Distinct GC-rich fragment end motifs are enriched after cfChIP.
Furthermore, distinct GC-rich FEMs were enriched after cfChIP.
Distinct GC-rich fragment end motifs are enriched after cfChIP.
Furthermore, distinct GC-rich FEMs were enriched after cfChIP.
Distinct GC-rich fragment end motifs are enriched after cfChIP.
Furthermore, distinct GC-rich FEMs were enriched after cfChIP.
Distinct GC-rich fragment end motifs are enriched after cfChIP.
Furthermore, distinct GC-rich FEMs were enriched after cfChIP.
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
p value 0.0001short cfDNA fragment enrichment among highest-expression genes 19.99 %short cfDNA fragment enrichment among highest-expression genes 16.94-27.13 %
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
combined-feature enrichment of most expressed genes 37.85 %combined-feature enrichment of most expressed genes 30.10-39.49 %p value 0.0001
In vitro size selection of <150 bp cfDNA can isolate cfDNA representing active genes, and the enrichment correlates with cfChIP-seq enrichment.
An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001).
p value 0.0001Spearman correlation with cfChIP-seq enrichment 0.499-0.882
In vitro size selection of <150 bp cfDNA can isolate cfDNA representing active genes, and the enrichment correlates with cfChIP-seq enrichment.
An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001).
p value 0.0001Spearman correlation with cfChIP-seq enrichment 0.499-0.882
In vitro size selection of <150 bp cfDNA can isolate cfDNA representing active genes, and the enrichment correlates with cfChIP-seq enrichment.
An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001).
p value 0.0001Spearman correlation with cfChIP-seq enrichment 0.499-0.882
In vitro size selection of <150 bp cfDNA can isolate cfDNA representing active genes, and the enrichment correlates with cfChIP-seq enrichment.
An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001).
p value 0.0001Spearman correlation with cfChIP-seq enrichment 0.499-0.882
In vitro size selection of <150 bp cfDNA can isolate cfDNA representing active genes, and the enrichment correlates with cfChIP-seq enrichment.
An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001).
p value 0.0001Spearman correlation with cfChIP-seq enrichment 0.499-0.882
In vitro size selection of <150 bp cfDNA can isolate cfDNA representing active genes, and the enrichment correlates with cfChIP-seq enrichment.
An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001).
p value 0.0001Spearman correlation with cfChIP-seq enrichment 0.499-0.882
In vitro size selection of <150 bp cfDNA can isolate cfDNA representing active genes, and the enrichment correlates with cfChIP-seq enrichment.
An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001).
p value 0.0001Spearman correlation with cfChIP-seq enrichment 0.499-0.882
In vitro size selection of <150 bp cfDNA can isolate cfDNA representing active genes, and the enrichment correlates with cfChIP-seq enrichment.
An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001).
p value 0.0001Spearman correlation with cfChIP-seq enrichment 0.499-0.882
In vitro size selection of <150 bp cfDNA can isolate cfDNA representing active genes, and the enrichment correlates with cfChIP-seq enrichment.
An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001).
p value 0.0001Spearman correlation with cfChIP-seq enrichment 0.499-0.882
In vitro size selection of <150 bp cfDNA can isolate cfDNA representing active genes, and the enrichment correlates with cfChIP-seq enrichment.
An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001).
p value 0.0001Spearman correlation with cfChIP-seq enrichment 0.499-0.882
Approval Evidence
1 source2 linked approval claimsfirst-pass slug cfdna-fragmentomics-evaluation
In this study, we conducted cfDNA fragmentomics evaluations using plasma from lung cancer patients (n = 12) and healthy individuals (n = 7).
Source:
associationsupports
Genes with the highest expression are enriched for short cfDNA fragments compared with genes with low expression.
The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression.
Source:
integration benefitsupports
Combining short cfDNA fragment frequency with distinct fragment end motifs further enriches for the most expressed genes.
Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001).
Source:
Comparisons
Source-backed strengths
The reported strength is multifeature integration: combining short cfDNA fragment frequency with distinct fragment end motifs further enriched for the most expressed genes. The study was applied to human plasma samples from both lung cancer patients (n = 12) and healthy individuals (n = 7), providing initial validation across two sample groups.
Compared with H3K36me3 cfChIP followed by droplet digital PCR
cfDNA fragmentomics evaluation and H3K36me3 cfChIP followed by droplet digital PCR address a similar problem space because they share selection.
Shared frame: same top-level item type; shared target processes: selection
Compared with high throughput screening
cfDNA fragmentomics evaluation and high throughput screening address a similar problem space because they share selection.
Shared frame: same top-level item type; shared target processes: selection
Compared with whole genome screening of gene knockout mutants
cfDNA fragmentomics evaluation and whole genome screening of gene knockout mutants address a similar problem space because they share selection.
Shared frame: same top-level item type; shared target processes: selection
Ranked Citations
- 1.