{"entity":{"id":"saferseqs","kind":"technology","name":"SaferSeqS (Watson and Crick strand sequencing)","aka":["SaferSeqS"],"tldr":"A way of reading both strands of each DNA molecule in a blood sample, so a real mutation can be told from a copying error even when only one molecule in 100,000 carries it.","summary":"SaferSeqS (Cohen et al., Nature Biotechnology 2021, Johns Hopkins) introduces identical molecular barcodes on the Watson and Crick strands of each template molecule and enriches targets with strand-specific PCR. It detects variants below 1 in 100,000 template molecules with a background mutation rate below 5 x 10^-7 mutants per base pair, can assess one or several amplicons, recovers both strands well from limited cell-free DNA, and cuts the error rate of existing barcoding approaches by more than 100-fold. It reaches that level per locus, for the few mutations it assays. Haystack MRD describes its chemistry as an optimised version of the earlier Safe-SeqS method from the same group.","status":"emerging","asOf":"2026-11-04","links":[{"label":"Cohen et al., Nat Biotechnol 2021 (SaferSeqS)","url":"https://doi.org/10.1038/s41587-021-00900-z"}],"tags":[],"related":["haystack-mrd","idea-same-fragment-methylation-and-mutation"],"cancers":[],"sections":["diagnostics"],"technologies":["mrd-testing","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","ngs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cohen-saferseqs-nat-biotechnol-2021"],"journals":[],"dependsOn":[],"notes":[],"principle":"A true mutation is present on both strands of a double-stranded molecule; an error made while copying is usually on one. Requiring both strands, tied together by barcodes, removes most errors.","strengths":["Error rate low enough to read single rare molecules","Works on small amounts of cell-free DNA"],"limitations":["Amplicon based: each assay reads few loci, so the total number of informative molecules is small","A per-locus limit, not a whole-sample limit"],"since":2021},"route":"/technologies/saferseqs/","neighbours":{"drug":[{"id":"haystack-mrd","kind":"drug","name":"Haystack MRD","route":"/drugs/haystack-mrd/"}],"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/"}],"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":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"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/"}],"paper":[{"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","route":"/key-papers/paper-cohen-saferseqs-nat-biotechnol-2021/"}]}}