ArticleClinical and translational medicine2024
Depletion-assisted multiplexed cell-free RNA sequencing reveals distinct human and microbial signatures in plasma versus extracellular vesicles.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Multifeature sequencing-based liquid biopsy for cancer diagnosis and monitoring.Genome medicine · 2026Review
- Single-cell transcriptomic analysis reveals that the circRNA circGCLM promotes tumorigenesis and confers cisplatin resistance in NSCLC through the miR-505-3p/ERBB4 axis.Translational oncology · 2026Article
- Circulating RNA as a Functional Component of Liquid Biopsy in Cancer: Concepts, Classification, and Clinical Applications.International journal of molecular sciences · 2026Review
- Wide-spectrum profiling of plasma cell-free RNA and the potential for health-monitoring.RNA biology · 2025Article
- Multi-omics data-based modeling reveals tumorigenesis- and prognosis-associated genes with clinical potential in lung adenocarcinoma.BMC cancer · 2025Article
- A promising frontier of circulating messenger RNA in liquid biopsy: From mechanisms to clinical applications.International journal of cancer · 2025Review
- Peak analysis of cell-free RNA finds recurrently protected narrow regions with clinical potential.Genome biology · 2025Article
- The glycolytic characteristics of hepatocellular carcinoma and its interaction with the microenvironment: a comprehensive omics study.Journal of translational medicine · 2025Article
- Advances in colorectal cancer screening: technological innovations, guideline discrepancies, and individualized strategies.Frontiers in oncology · 2025Review
- A ligation-independent sequencing method reveals tRNA-derived RNAs with blocked 3' termini.Molecular cell · 2024Article
- Depletion-assisted multiplexed cell-free RNA sequencing reveals distinct human and microbial signatures in plasma versus extracellular vesicles.Clinical and translational medicine · 2024Article
- Decoding cell-type contributions to the cfRNA transcriptomic landscape of liver cancer.Human genomics · 2023Article
- A ligation-independent sequencing method reveals tRNA-derived RNAs with blocked 3' termini.bioRxiv : the preprint server for biology · 2023Article
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14 authors.
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Abstract
backgroundCell-free long RNAs in human plasma and extracellular vesicles (EVs) have shown promise as biomarkers in liquid biopsy, despite their fragmented nature.
methodsTo investigate these fragmented cell-free RNAs (cfRNAs), we developed a cost-effective cfRNA sequencing method called DETECTOR-seq (depletion-assisted multiplexed cell-free total RNA sequencing). DETECTOR-seq utilised a meticulously tailored set of customised guide RNAs to remove large amounts of unwanted RNAs (i.e., fragmented ribosomal and mitochondrial RNAs) in human plasma. Early barcoding strategy was implemented to reduce costs and minimise plasma requirements.
resultsUsing DETECTOR-seq, we conducted a comprehensive analysis of cell-free transcriptomes in both whole human plasma and EVs. Our analysis revealed discernible distributions of RNA types in plasma and EVs. Plasma exhibited pronounced enrichment in structured circular RNAs, tRNAs, Y RNAs and viral RNAs, while EVs showed enrichment in messenger RNAs (mRNAs) and signal recognition particle RNAs (srpRNAs). Functional pathway analysis highlighted RNA splicing-related ribonucleoproteins (RNPs) and antimicrobial humoral response genes in plasma, while EVs demonstrated enrichment in transcriptional activity, cell migration and antigen receptor-mediated immune signals. Our study indicates the comparable potential of cfRNAs from whole plasma and EVs in distinguishing cancer patients (i.e., colorectal and lung cancer) from healthy donors. And microbial cfRNAs in plasma showed potential in classifying specific cancer types.
conclusionsOur comprehensive analysis of total and EV cfRNAs in paired plasma samples provides valuable insights for determining the need for EV purification in cfRNA-based studies. We envision the cost effectiveness and efficiency of DETECTOR-seq will empower transcriptome-wide investigations in the fields of cfRNAs and liquid biopsy. KEYPOINTS: DETECTOR-seq (depletion-assisted multiplexed cell-free total RNA sequencing) enabled efficient and specific depletion of sequences derived from fragmented ribosomal and mitochondrial RNAs in plasma. Distinct human and microbial cell-free RNA (cfRNA) signatures in whole Plasma versus extracellular vesicles (EVs) were revealed. Both Plasma and EV cfRNAs were capable of distinguishing cancer patients from normal individuals, while microbial RNAs in Plasma cfRNAs enabled better classification of cancer types than EV cfRNAs.
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