ArticleNucleic acids research2016
Elimination of unaltered DNA in mixed clinical samples via nuclease-assisted minor-allele enrichment.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 77 citations in OpenAlex.
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- An Integrated Strategy for Analyzing the Complete Complex Integrated Structure of Maize MON810 and Identification of an SNP in External Insertion Sequences.Plants (Basel, Switzerland) · 2024Article
- Combining E-ice-COLD-PCR and Pyrosequencing with Di-Base Addition (PDBA) Enables Sensitive Detection of Low-Abundance Mutations.Applied biochemistry and biotechnology · 2024Article
- Detection of low-frequency mutations in clinical samples by increasing mutation abundance via the excision of wild-type sequences.Nature biomedical engineering · 2023Article
- Circulating tumour DNA alterations: emerging biomarker in head and neck squamous cell carcinoma.Journal of biomedical science · 2023Review
- Enzymatic Methods for Mutation Detection in Cancer Samples and Liquid Biopsies.International journal of molecular sciences · 2023Review
- Nuclease Enrichment and qPCR Detection of Rare Nucleotide Variants.Methods in molecular biology (Clifton, N.J.) · 2023Article
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- Mutation enrichment in human DNA samples via UV-mediated cross-linking.Nucleic acids research · 2022Article
- Limitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics.Nature biomedical engineering · 2022Review
- Massively parallel enrichment of low-frequency alleles enables duplex sequencing at low depth.Nature biomedical engineering · 2022Article
- Multiplex SuperSelective PCR Assays for the Detection and Quantitation of Rare Somatic Mutations in Liquid Biopsies.The Journal of molecular diagnostics : JMD · 2022Article
- Nuclease-Assisted, Multiplexed Minor-Allele Enrichment: Application in Liquid Biopsy of Cancer.Methods in molecular biology (Clifton, N.J.) · 2022Article
- CRISPR Cas9-Mediated Selective Isothermal Amplification for Sensitive Detection of Rare Mutant Alleles.Clinical chemistry · 2021Article
- Argonaute integrated single-tube PCR system enables supersensitive detection of rare mutations.Nucleic acids research · 2021Article
- Review
- Selective multiplexed enrichment for the detection and quantitation of low-fraction DNA variants via low-depth sequencing.Nature biomedical engineering · 2021Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Presence of excess unaltered, wild-type (WT) DNA providing no information of biological or clinical value often masks rare alterations containing diagnostic or therapeutic clues in cancer, prenatal diagnosis, infectious diseases or organ transplantation. With the surge of high-throughput technologies there is a growing demand for removing unaltered DNA over large pools-of-sequences. Here we present nuclease-assisted minor-allele enrichment with probe-overlap (NaME-PrO), a single-step approach with broad genome coverage that can remove WT-DNA from numerous sequences simultaneously, prior to genomic analysis. NaME-PrO employs a double-strand-DNA-specific nuclease and overlapping oligonucleotide-probes interrogating WT-DNA targets and guiding nuclease digestion to these sites. Mutation-containing DNA creates probe-DNA mismatches that inhibit digestion, thus subsequent DNA-amplification magnifies DNA-alterations at all selected targets. We demonstrate several-hundred-fold mutation enrichment in diverse human samples on multiple clinically relevant targets including tumor samples and circulating DNA in 50-plex reactions. Enrichment enables routine mutation detection at 0.01% abundance while by adjusting conditions it is possible to sequence mutations down to 0.00003% abundance, or to scan tumor-suppressor genes for rare mutations. NaME-PrO introduces a simple and highly parallel process to remove un-informative DNA sequences and unmask clinically and biologically useful alterations.
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Registered trials
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