Bounded definition
The cited study develops GUIDE-seq and applies it to specified RNA-guided nucleases in two human cell lines. Within this page, that proposition is 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.
Definition and evidence boundary
A cell-based sequencing method that captures double-strand oligonucleotides at nuclease-induced DNA breaks to nominate off-target sites. The bounded proposition retained by the canonical record is: The cited study develops GUIDE-seq and applies it to specified RNA-guided nucleases in two human cell lines.
The applicable scope is 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 definition must not be generalized beyond the cited source and exact record boundary.
Claims: urn:maha:claim:guide-seq-off-target-detection
Mechanism and technical context
The study develops GUIDE-seq, a cell-based double-strand-break capture method, and applies it to specified nucleases and human cell lines. This is the source-bound technical context for the record; no uncited mechanism is added by the compiler.
Assay sensitivity depends on break capture, cell compatibility, sequencing, analysis, and the nuclease modality under study. The mechanism or method is therefore presented as one component of a larger system, not as evidence for every downstream outcome.
Claims: urn:maha:claim:guide-seq-off-target-detection
How to interpret the evidence
There is no universal effect estimate for this method; numerical results remain attached to the source experiment, biological system, assay, and analysis choices. The evidence maturity recorded here is single study, and the claim kind is empirical claim.
This candidate records one bounded source package. Independent replications and contradictory results must be compiled separately before evidence maturity is upgraded. GUIDE-seq has assay-specific detection limits and dependencies and does not nominate every possible off-target event in every biological context. These qualifications travel with the claim whenever it is reused.
Claims: urn:maha:claim:guide-seq-off-target-detection
What the source supports and what remains unknown
The inspected source supports exactly this: The study develops GUIDE-seq, a cell-based double-strand-break capture method, and applies it to specified nucleases and human cell lines. It was read at Abstract; Figures 1–6; Online Methods; Supplementary Tables; Sequence Read Archive SRP050338.
What remains unknown is everything outside that locator. Assay sensitivity depends on break capture, cell compatibility, sequencing, analysis, and the nuclease modality under study. No quantity, comparison, or downstream outcome is established here unless a separately scoped record measures it.
Claims: urn:maha:claim:guide-seq-off-target-detection
Source identity, locator, and reuse boundary
The bound source is “GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases” by Shengdar Q. Tsai, Zongli Zheng, Nhu T. Nguyen, Matthew Liebers, et al., published by Nature Biotechnology on 2014-12-16; its declared stable identity is doi:10.1038/nbt.3117.
The inspected-content locator is Abstract; Figures 1–6; Online Methods; Supplementary Tables; Sequence Read Archive SRP050338. Reuse is limited to citation-with-paraphrase. Maha paraphrases the source-level result and links to the version of record; no article passage is reproduced. This metadata establishes source identity and inspection scope, not the truth of claims outside the cited locator.
Claims: urn:maha:claim:guide-seq-off-target-detection
Comparison and calculation boundary
Applicability is decided explicitly, not filled with generic material.
This record carries 1 source-bound proposition and therefore has no second supported side. A comparison would have to be manufactured from an adjacent title rather than from a second inspected claim, which the gate forbids.
The canonical claim declares no reproducible numerical inputs, equation, units, or uncertainty propagation; recorded uncertainty kind is qualitative. Supplying sample values would invent an unsupported quantitative result.
Limitations and prohibited inference
The claim stops where its evidence stops.
- record boundary
Assay sensitivity depends on break capture, cell compatibility, sequencing, analysis, and the nuclease modality under study.
- record boundary
A source-bounded mechanism, method, or measurement record does not establish manufacturing yield, economic advantage, safety, clinical benefit, or commercial readiness unless those outcomes are measured in a separately scoped record.
- prohibited inference
Do not treat the guide-seq off-target detection record as medical advice, a treatment recommendation, or evidence of general clinical readiness.
- prohibited inference
Do not transfer a reported result across hardware, organisms, protocols, datasets, operating conditions, or outcome definitions without a declared comparison contract.
- editorial
This compilation reorganizes an existing inspected claim and its declared source; it does not add a new experiment, measurement, or independent replication.
- editorial
Internal editorial inspection is not external peer review, and no result on this page has been independently reproduced.
Related records and mathematical bridges
Typed links expose context without asserting equivalence.
Adenine base editing
Same canonical domain (synthetic-biology). Domain membership only: no shared source or declared edge links these two records.
Selection: domain adjacency
Off-target nomination versus confirmation
Declared mechanistic-dependency edge from this record. The edge is navigational and asserts no equivalence or causation beyond the cited source scope.
Selection: bridge edge
Targeted amplicon sequencing of edit outcomes
Cites the same source as this record, so the two are related through the evidence rather than through wording.
Selection: shared source
When no declared bridge edge is present, related records are linked by shared evidence or canonical domain adjacency. Those links are navigational and do not claim mathematical or physical equivalence.
Connected domain graph
Typed dependencies preserve publication state.
Only independently canonical records receive public links and relation statements. Draft graph topology remains private.
Off-target nomination versus confirmation
outbound connection · comparison
GUIDE-seq produces a nomination set that requires orthogonal confirmation and frequency measurement.
Off-target nomination versus confirmation
inbound connection · comparison
GUIDE-seq provides a cell-based nomination channel.
Claim ledger
Every proposition keeps its own evidence state.
The cited study develops GUIDE-seq and applies it to specified RNA-guided nucleases in two human cell lines.
- 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.
- Uncertainty
- There is no universal effect estimate for this method; numerical results remain attached to the source experiment, biological system, assay, and analysis choices.
- Replication
- This candidate records one bounded source package. Independent replications and contradictory results must be compiled separately before evidence maturity is upgraded.
Primary sources
Citation, locator, rights, and boundary travel together.
Source 1 · Nature Biotechnology
GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases
Shengdar Q. Tsai, Zongli Zheng, Nhu T. Nguyen, Matthew Liebers, et al.
- Exact locator
- Abstract; Figures 1–6; Online Methods; Supplementary Tables; Sequence Read Archive SRP050338.
- Establishes
- The study develops GUIDE-seq, a cell-based double-strand-break capture method, and applies it to specified nucleases and human cell lines.
- Boundary
- GUIDE-seq has assay-specific detection limits and dependencies and does not nominate every possible off-target event in every biological context.
- Rights basis
- citation with paraphrase · Maha paraphrases the source-level result and links to the version of record; no article passage is reproduced.