{"entity":{"id":"paper-cohen-saferseqs-nat-biotechnol-2021","kind":"paper","name":"Detection of low-frequency DNA variants by targeted sequencing of the Watson and Crick strands","aka":[],"tldr":"Barcoding both strands of each DNA molecule let researchers find mutations carried by fewer than 1 in 100,000 molecules.","summary":"SaferSeqS introduces identical molecular barcodes into the Watson and Crick strands of template molecules and enriches targets by strand-specific PCR. It detects variants at frequencies below 1 in 100,000 DNA template molecules with a background mutation rate below 5 x 10^-7 mutants per base pair, can evaluate one or several amplicons, assesses limited quantities of cell-free DNA with high recovery of both strands, and reduces the error rate of existing PCR-based barcoding by more than 100-fold.","asOf":"2026-11-04","links":[{"label":"Cohen et al., Nat Biotechnol 2021","url":"https://doi.org/10.1038/s41587-021-00900-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33941929/"}],"tags":[],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["saferseqs","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","ngs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-biotechnology"],"dependsOn":[],"notes":[],"journal":"Nature Biotechnology","year":2021,"doi":"10.1038/s41587-021-00900-z","pmid":"33941929","authors":"Cohen JD, Douville C, Dudley JC, et al.","paperType":"methods","findings":["Variants detected below 1 in 100,000 template molecules.","Background below 5 x 10^-7 mutants per base pair.","More than 100-fold lower error than earlier barcoding."],"whatItMeans":"Error is no longer what stops a blood test reading one rare molecule; how many molecules there are is.","caveats":["Per-amplicon performance; few loci per assay."]},"route":"/key-papers/paper-cohen-saferseqs-nat-biotechnol-2021/","neighbours":{"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"saferseqs","kind":"technology","name":"SaferSeqS (Watson and Crick strand sequencing)","route":"/technologies/saferseqs/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"journal":[{"id":"nature-biotechnology","kind":"journal","name":"Nature Biotechnology","route":"/journals/nature-biotechnology/"}],"idea":[{"id":"idea-same-fragment-methylation-and-mutation","kind":"idea","name":"Read methylation and mutation on the same cell-free DNA fragment to tell what kind of cancer is left","route":"/ideas/idea-same-fragment-methylation-and-mutation/"}]}}