{"schemaVersion":"maha-epistemic/1.0","evidencePolicyVersion":"mps/0.1","recordId":"urn:maha:record:guide-seq-off-target-detection","canonicalPath":"/knowledge/synthetic-biology/methods/guide-seq-off-target-detection","contentHash":"sha256:b738f5e6d5ec6fe626627038e22ded237d4b4def829b9460dcbb68e4da8b6c2e","generatedAt":"2026-08-30T16:02:48.549Z","publicationDecision":{"recordId":"urn:maha:record:guide-seq-off-target-detection","publicEligible":true,"evaluatedAgainst":"maha-epistemic/1.0","reasons":[]},"claims":[{"id":"urn:maha:claim:guide-seq-off-target-detection","scope":"The constructs, biological systems, protocols, assays, datasets, and comparisons reported in GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases.","boundary":"Assay sensitivity depends on break capture, cell compatibility, sequencing, analysis, and the nuclease modality under study.","claimKind":"empirical-claim","sourceIds":["source-tsai-guide-seq-2015"],"statement":"The cited study develops GUIDE-seq and applies it to specified RNA-guided nucleases in two human cell lines.","replication":{"asOfDate":"2026-08-24","assessment":"This candidate records one bounded source package. Independent replications and contradictory results must be compiled separately before evidence maturity is upgraded.","independentReplicationCount":null},"uncertainty":{"kind":"qualitative","statement":"There is no universal effect estimate for this method; numerical results remain attached to the source experiment, biological system, assay, and analysis choices."},"evidenceMaturity":"single-study"}],"sources":[{"id":"source-tsai-guide-seq-2015","url":"https://www.nature.com/articles/nbt.3117","title":"GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases","rights":{"note":"Maha paraphrases the source-level result and links to the version of record; no article passage is reproduced.","basis":"citation-with-paraphrase","quotationUsed":false},"authors":["Shengdar Q. Tsai","Zongli Zheng","Nhu T. Nguyen","Matthew Liebers","et al."],"boundary":"GUIDE-seq has assay-specific detection limits and dependencies and does not nominate every possible off-target event in every biological context.","publisher":"Nature Biotechnology","establishes":"The study develops GUIDE-seq, a cell-based double-strand-break capture method, and applies it to specified nucleases and human cell lines.","identifiers":[{"value":"10.1038/nbt.3117","scheme":"doi"}],"publishedAt":"2014-12-16","exactLocator":"Abstract; Figures 1–6; Online Methods; Supplementary Tables; Sequence Read Archive SRP050338."}],"reviewEvents":[{"scope":"source-fidelity","verdict":"approve","reviewId":"epireview_9938dfdd2e0646bba52c388a518bf7a7","rationale":"GUIDE-seq off-target detection binds claim urn:maha:claim:guide-seq-off-target-detection only to GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases at PMC4320685 author manuscript, Abstract and “Overview of the GUIDE-seq method”. The audit inspected repository-copy at bounded inspected artifact depth and recorded subject and claim support; the claim remains limited to “The constructs, biological systems, protocols, assays, datasets, and comparisons reported in GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases.”. This decision applies only to record urn:maha:record:guide-seq-off-target-detection at sha256:5ef01b9f49fc3c5f1c6fcf4afefc0530f809cabbd9c9dc75a255f737081a0e24 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:01.646Z","reviewerId":"expert_maha-internal-editorial-scale-v1","reviewMethod":"Each criterion is recomputed from the exact record, its inspected alignment audit, source identity, exact locator, rights basis, claim scope, boundary, uncertainty, replication status, prohibited inferences, and revision digest.","reviewerKind":"internal-editorial","reviewerRole":"AI-assisted record-specific review of inspected source identity, exact locator, bounded claim, uncertainty, non-claims, rights basis, and exact revision. 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This decision applies only to record urn:maha:record:guide-seq-off-target-detection at sha256:5ef01b9f49fc3c5f1c6fcf4afefc0530f809cabbd9c9dc75a255f737081a0e24 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:01.774Z","reviewerId":"expert_maha-internal-editorial-scale-v1","reviewMethod":"Each criterion is recomputed from the exact record, its inspected alignment audit, source identity, exact locator, rights basis, claim scope, boundary, uncertainty, replication status, prohibited inferences, and revision digest.","reviewerKind":"internal-editorial","reviewerRole":"AI-assisted record-specific review of inspected source identity, exact locator, bounded claim, uncertainty, non-claims, rights basis, and exact revision. This is not an external subject-matter credential.","targetSha256":"sha256:5ef01b9f49fc3c5f1c6fcf4afefc0530f809cabbd9c9dc75a255f737081a0e24","supersedesReviewId":null,"reviewerProfileVersion":1},{"scope":"boundary-adequacy","verdict":"approve","reviewId":"epireview_6eabb49ec4f142f9adf079d2762c0cfa","rationale":"GUIDE-seq off-target detection retains uncertainty “There is no universal effect estimate for this method; numerical results remain attached to the source experiment, biological system, assay, and analysis choices.” and replication assessment “This candidate records one bounded source package. Independent replications and contradictory results must be compiled separately before evidence maturity is upgraded.”. Its non-claims and 2 prohibited inference(s) remain attached to every reuse. This decision applies only to record urn:maha:record:guide-seq-off-target-detection at sha256:5ef01b9f49fc3c5f1c6fcf4afefc0530f809cabbd9c9dc75a255f737081a0e24 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:01.846Z","reviewerId":"expert_maha-internal-editorial-scale-v1","reviewMethod":"Each criterion is recomputed from the exact record, its inspected alignment audit, source identity, exact locator, rights basis, claim scope, boundary, uncertainty, replication status, prohibited inferences, and revision digest.","reviewerKind":"internal-editorial","reviewerRole":"AI-assisted record-specific review of inspected source identity, exact locator, bounded claim, uncertainty, non-claims, rights basis, and exact revision. This is not an external subject-matter credential.","targetSha256":"sha256:5ef01b9f49fc3c5f1c6fcf4afefc0530f809cabbd9c9dc75a255f737081a0e24","supersedesReviewId":null,"reviewerProfileVersion":1},{"scope":"rights-and-locator","verdict":"approve","reviewId":"epireview_e54c201fa9d943aab2ec73e91489abe8","rationale":"GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases is identified by doi:10.1038/nbt.3117, inspected at Abstract; Figures 1–6; Online Methods; Supplementary Tables; Sequence Read Archive SRP050338., and retained under citation-with-paraphrase. This approval binds only exact revision sha256:5ef01b9f49fc3c5f1c6fcf4afefc0530f809cabbd9c9dc75a255f737081a0e24. This decision applies only to record urn:maha:record:guide-seq-off-target-detection at sha256:5ef01b9f49fc3c5f1c6fcf4afefc0530f809cabbd9c9dc75a255f737081a0e24 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:01.922Z","reviewerId":"expert_maha-internal-editorial-scale-v1","reviewMethod":"Each criterion is recomputed from the exact record, its inspected alignment audit, source identity, exact locator, rights basis, claim scope, boundary, uncertainty, replication status, prohibited inferences, and revision digest.","reviewerKind":"internal-editorial","reviewerRole":"AI-assisted record-specific review of inspected source identity, exact locator, bounded claim, uncertainty, non-claims, rights basis, and exact revision. This is not an external subject-matter credential.","targetSha256":"sha256:5ef01b9f49fc3c5f1c6fcf4afefc0530f809cabbd9c9dc75a255f737081a0e24","supersedesReviewId":null,"reviewerProfileVersion":1}]}