ArticleNature biomedical engineering2021
Selective multiplexed enrichment for the detection and quantitation of low-fraction DNA variants via low-depth sequencing.
Article in Nature biomedical engineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 67 citations in OpenAlex.
- Anchored random reverse primer sequencing for quantitative detection of novel gene fusions.Nature biomedical engineering · 2026Article
- High-throughput evaluation of in vitro CRISPR activities enables optimized large-scale multiplex enrichment of rare variants.Nature biomedical engineering · 2026Article
- Confirmation of Exome Sequencing Results Using Sanger Sequencing-Considerations in a Low-Resource Setting.Molecular genetics & genomic medicine · 2026Article
- Machine learning-directed massively parallel programmable nucleic acid amplification.Science advances · 2026Article
- Benchmarking UMI clustering tools for accurate detection of low-frequency variants from deep sequencing.Scientific reports · 2025Article
- Comprehensive genomic profiling of Taiwanese triple-negative breast cancer samples with medium- and large-sized sequencing panels: A comparative study implicating treatment allocations.Biomedical reports · 2025Article
- Methods Established forPlants (Basel, Switzerland) · 2025Article
- Article
- Reaction Pathway Differentiation Enabled Fingerprinting Signal for Single Nucleotide Variant Detection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oligonucleotide subsets selection by single nucleotide resolution barcode identification.Nature communications · 2025Article
- Advancing quantitative PCR with color cycle multiplex amplification.Nucleic acids research · 2024Article
- Mutational variant allele frequency profile as a biomarker of response to immune checkpoint blockade in non-small cell lung Cancer.Journal of translational medicine · 2024Article
- Recent advances in enzyme-free and enzyme-mediated single-nucleotide variation assayNational science review · 2024Review
- Detection of low-frequency mutations in clinical samples by increasing mutation abundance via the excision of wild-type sequences.Nature biomedical engineering · 2023Article
- Evaluation of the Analytical Performance of Oncomine Lung cfDNA Assay for Detection of PlasmaGenes · 2023Article
- Inferring parameters of cancer evolution in chronic lymphocytic leukemia.PLoS computational biology · 2022Article
- Limitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics.Nature biomedical engineering · 2022Review
- Cell-free DNA technologies for the analysis of brain cancer.British journal of cancer · 2022Review
- Calibration-free NGS quantitation of mutations below 0.01% VAF.Nature communications · 2021Article
- Oncogene Concatenated Enriched Amplicon Nanopore Sequencing for rapid, accurate, and affordable somatic mutation detection.Genome biology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
DNA sequence variants with allele fractions below 1% are difficult to detect and quantify by sequencing owing to intrinsic errors in sequencing-by-synthesis methods. Although molecular-identifier barcodes can detect mutations with a variant-allele frequency (VAF) as low as 0.1% using next-generation sequencing (NGS), sequencing depths of over 25,000× are required, thus hampering the detection of mutations at high sensitivity in patient samples and in most samples used in research. Here we show that low-frequency DNA variants can be detected via low-depth multiplexed NGS after their amplification, by a median of 300-fold, using polymerase chain reaction and rationally designed 'blocker' oligonucleotides that bind to the variants. Using an 80-plex NGS panel and a sequencing depth of 250×, we detected single nucleotide polymorphisms with a VAF of 0.019% and contamination in human cell lines at a VAF as low as 0.07%. With a 16-plex NGS panel covering 145 mutations across 9 genes involved in melanoma, we detected low-VAF mutations (0.2-5%) in 7 out of the 19 samples of freshly frozen tumour biopsies, suggesting that tumour heterogeneity could be notably higher than previously recognized.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.