ArticleClinical chemistry2021
Measurement Biases Distort Cell-Free DNA Fragmentation Profiles and Define the Sensitivity of Metagenomic Cell-Free DNA Sequencing Assays.
Article in Clinical chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Clinical utility of serial plasma cell-free DNA metagenomic next-generation sequencing assays.Infection control and hospital epidemiology · 2026Observational
- Metagenomic Cell-free DNA Sequencing for Treatment Monitoring in Sepsis.Research square · 2025Article
- Bacterial cell-free DNA profiling reveals the co-elevation of multiple bacteria in newborn foals with suspected sepsis.iScience · 2025Article
- In-matrix library preparation for metagenomic sequencing of microbial cell-free DNA.Journal of clinical microbiology · 2025Article
- Circulating Cell-Free DNA as an Epigenetic Biomarker for Early Diabetic Retinopathy: A Narrative Review.Diagnostics (Basel, Switzerland) · 2025Review
- Enrichment of Microbial DNA in Plasma to Improve Pathogen Detection in Sepsis: A Pilot Study.Clinical chemistry · 2025Article
- Unleashing the power of urine‑based biomarkers in diagnosis, prognosis and monitoring of bladder cancer (Review).International journal of oncology · 2025Review
- Circulating DNA fragmentomics and cancer screening.Cell genomics · 2023Review
- Metagenomic DNA sequencing to quantify Mycobacterium tuberculosis DNA and diagnose tuberculosis.Scientific reports · 2022Article
- A metagenomic DNA sequencing assay that is robust against environmental DNA contamination.Nature communications · 2022Article
- A metagenomic DNA sequencing assay that is robust against environmental DNA contamination.bioRxiv : the preprint server for biology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundMetagenomic sequencing of microbial cell-free DNA (cfDNA) in blood and urine is increasingly used as a tool for unbiased infection screening. The sensitivity of metagenomic cfDNA sequencing assays is determined by the efficiency by which the assay recovers microbial cfDNA vs host-specific cfDNA. We hypothesized that the choice of methods used for DNA isolation, DNA sequencing library preparation, and sequencing would affect the sensitivity of metagenomic cfDNA sequencing.
methodsWe characterized the fragment length biases inherent to select DNA isolation and library preparation procedures and developed a model to correct for these biases. We analyzed 305 cfDNA sequencing data sets, including publicly available data sets and 124 newly generated data sets, to evaluate the dependence of the sensitivity of metagenomic cfDNA sequencing on pre-analytical variables.
resultsLength bias correction of fragment length distributions measured from different experimental procedures revealed the ultrashort (<100 bp) nature of microbial-, mitochondrial-, and host-specific urinary cfDNA. The sensitivity of metagenomic sequencing assays to detect the clinically reported microorganism differed by more than 5-fold depending on the combination of DNA isolation and library preparation used.
conclusionsSubstantial gains in the sensitivity of microbial and other short fragment recovery can be achieved by easy-to-implement changes in the sample preparation protocol, which highlights the need for standardization in the liquid biopsy field.
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