{"doi":"10.1038/s41564-021-01019-2","title":"Synthetic DNA spike-ins (SDSIs) enable sample tracking and detection of inter-sample contamination in SARS-CoV-2 sequencing workflows","abstract":"The global spread and continued evolution of SARS-CoV-2 has driven an unprecedented surge in viral genomic surveillance. Amplicon-based sequencing methods provide a sensitive, low-cost and rapid approach but suffer a high potential for contamination, which can undermine laboratory processes and results. This challenge will increase with the expanding global production of sequences across a variety of laboratories for epidemiological and clinical interpretation, as well as for genomic surveillance of emerging diseases in future outbreaks. We present SDSI + AmpSeq, an approach that uses 96 synthetic DNA spike-ins (SDSIs) to track samples and detect inter-sample contamination throughout the sequencing workflow. We apply SDSIs to the ARTIC Consortium's amplicon design, demonstrate their utility and efficiency in a real-time investigation of a suspected hospital cluster of SARS-CoV-2 cases and validate them across 6,676 diagnostic samples at multiple laboratories. We establish that SDSI + AmpSeq provides increased confidence in genomic data by detecting and correcting for relatively common, yet previously unobserved modes of error, including spillover and sample swaps, without impacting genome recovery.","journal":"Nature Microbiology","year":2021,"id":180858,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":472080,"name":"Erica Normandin","orcid":"0000-0002-4996-6442","position":1,"is_corresponding":false},{"id":554217,"name":"Matthew R. 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Dewey","orcid":null,"position":10,"is_corresponding":false},{"id":730978,"name":"Susan Kales","orcid":"0000-0002-9903-7027","position":11,"is_corresponding":false},{"id":731770,"name":"Sabrina T. Dobbins","orcid":null,"position":12,"is_corresponding":false},{"id":303843,"name":"Erica S. Shenoy","orcid":"0000-0001-8086-1123","position":13,"is_corresponding":false},{"id":237091,"name":"David C. Hooper","orcid":"0000-0002-1444-9939","position":14,"is_corresponding":false},{"id":257713,"name":"Virginia Pierce","orcid":"0000-0002-3723-1326","position":15,"is_corresponding":false},{"id":731771,"name":"Kimon C. Zachary","orcid":null,"position":16,"is_corresponding":false},{"id":251090,"name":"Daniel J. Park","orcid":"0000-0001-7226-7781","position":17,"is_corresponding":false},{"id":226713,"name":"Bronwyn MacInnis","orcid":"0000-0003-0082-968X","position":18,"is_corresponding":false},{"id":3034,"name":"Ryan Tewhey","orcid":"0000-0002-4607-8001","position":19,"is_corresponding":false},{"id":226714,"name":"Jacob E. Lemieux","orcid":"0000-0002-2758-4005","position":20,"is_corresponding":false},{"id":7155,"name":"Pardis C. Sabeti","orcid":"0000-0002-9843-1890","position":21,"is_corresponding":false},{"id":3036,"name":"Steven K. Reilly","orcid":"0000-0003-3140-1483","position":22,"is_corresponding":false},{"id":251084,"name":"Katherine J. Siddle","orcid":"0000-0002-1799-7295","position":23,"is_corresponding":false},{"id":371202,"name":"Kim A. Lagerborg","orcid":"0000-0003-2490-2191","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:48:01.257885Z","pmid":"34907347","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}