{"schemaVersion":"maha-epistemic/1.0","evidencePolicyVersion":"mps/0.1","recordId":"urn:maha:record:off-target-nomination-versus-confirmation","canonicalPath":"/knowledge/synthetic-biology/comparisons/off-target-nomination-versus-confirmation","contentHash":"sha256:4a1ca166e9fa96cd9fb93104466f3af46e3535a5d03348edcdc2fa1ee5b617f5","generatedAt":"2026-08-30T16:02:53.632Z","publicationDecision":{"recordId":"urn:maha:record:off-target-nomination-versus-confirmation","publicEligible":true,"evaluatedAgainst":"maha-epistemic/1.0","reasons":[]},"claims":[{"id":"urn:maha:claim:off-target-nomination-versus-confirmation","scope":"The constructs, biological systems, protocols, assays, datasets, and comparisons reported in CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity.","boundary":"A nominated site is not automatically edited in cells, while a non-nominated site is not proof of absolute absence below every detection limit.","claimKind":"empirical-claim","sourceIds":["source-lazzarotto-change-seq-2020"],"statement":"The cited study compares in-vitro CHANGE-seq nominations with cellular off-target activity and shows that genomic context and individual variation affect correspondence.","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-lazzarotto-change-seq-2020","url":"https://www.nature.com/articles/s41587-020-0555-7","title":"CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity","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":["Christopher R. Lazzarotto","Nhu T. Nguyen","J. A. Tangprasertchai","S. C. Malagon-Lopez","et al."],"boundary":"In-vitro nomination is not identical to editing frequency or biological consequence in a treated cell population or organism.","publisher":"Nature Biotechnology","establishes":"The study develops an in-vitro circularized-DNA assay for Cas9 activity and compares nominations with cellular activity and genomic context for specified targets.","identifiers":[{"value":"10.1038/s41587-020-0555-7","scheme":"doi"}],"publishedAt":"2020-06-22","exactLocator":"Abstract; Figures 1–6; Methods; datasets PRJNA625995 and GSE149295.","conflictsOfInterest":"The article declares patent and company relationships involving genome-editing assays and therapeutics."}],"reviewEvents":[{"scope":"source-fidelity","verdict":"approve","reviewId":"epireview_23a4444de1834a46b4c2accb3d69f4d8","rationale":"Off-target nomination versus confirmation binds claim urn:maha:claim:off-target-nomination-versus-confirmation only to CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity at PMC7652380 author manuscript, Abstract; activity profiling; chromatin-state sections. 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 CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity.”. This decision applies only to record urn:maha:record:off-target-nomination-versus-confirmation at sha256:b7bced5f8d14674ed18063921b7fa6f4acdab6e3de8b01c51c413a7f02bd7f55 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:02.935Z","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:b7bced5f8d14674ed18063921b7fa6f4acdab6e3de8b01c51c413a7f02bd7f55","supersedesReviewId":null,"reviewerProfileVersion":1},{"scope":"domain-fidelity","verdict":"approve","reviewId":"epireview_c58a89f4c2364495a3bb36e80f637fa0","rationale":"Off-target nomination versus confirmation remains within domain synthetic-biology. Its mechanism or method is the bounded proposition “The cited study compares in-vitro CHANGE-seq nominations with cellular off-target activity and shows that genomic context and individual variation affect correspondence.”; the record does not transfer that proposition beyond A nominated site is not automatically edited in cells, while a non-nominated site is not proof of absolute absence below every detection limit. This decision applies only to record urn:maha:record:off-target-nomination-versus-confirmation at sha256:b7bced5f8d14674ed18063921b7fa6f4acdab6e3de8b01c51c413a7f02bd7f55 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:03.001Z","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:b7bced5f8d14674ed18063921b7fa6f4acdab6e3de8b01c51c413a7f02bd7f55","supersedesReviewId":null,"reviewerProfileVersion":1},{"scope":"boundary-adequacy","verdict":"approve","reviewId":"epireview_b16a38aec43f48cea9c576da8d1e1500","rationale":"Off-target nomination versus confirmation 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:off-target-nomination-versus-confirmation at sha256:b7bced5f8d14674ed18063921b7fa6f4acdab6e3de8b01c51c413a7f02bd7f55 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:03.070Z","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:b7bced5f8d14674ed18063921b7fa6f4acdab6e3de8b01c51c413a7f02bd7f55","supersedesReviewId":null,"reviewerProfileVersion":1},{"scope":"rights-and-locator","verdict":"approve","reviewId":"epireview_cbf3fe5b4cad49168d58023fa3e7864f","rationale":"CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity is identified by doi:10.1038/s41587-020-0555-7, inspected at Abstract; Figures 1–6; Methods; datasets PRJNA625995 and GSE149295., and retained under citation-with-paraphrase. This approval binds only exact revision sha256:b7bced5f8d14674ed18063921b7fa6f4acdab6e3de8b01c51c413a7f02bd7f55. This decision applies only to record urn:maha:record:off-target-nomination-versus-confirmation at sha256:b7bced5f8d14674ed18063921b7fa6f4acdab6e3de8b01c51c413a7f02bd7f55 and does not certify truth, external endorsement, independent reproduction, or fitness for use.","reviewedAt":"2026-08-30T16:02:03.287Z","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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