published-canonicalcomparisonmaha-epistemic/1.0

Off-target nomination versus confirmation

A distinction between assays that identify candidate sites and cellular measurements that confirm editing frequency under matched conditions. This candidate preserves the experimental unit—editor or circuit, target, cell system, delivery, protocol, assay, comparator, and observation window—before any broader inference is considered.

Bounded definition

A distinction between assays that identify candidate sites and cellular measurements that confirm editing frequency under matched conditions.

What the cited work 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.

The constructs, biological systems, protocols, assays, datasets, and comparisons reported in CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity.

Claims: urn:maha:claim:off-target-nomination-versus-confirmation

What remains a separate question

A nominated site is not automatically edited in cells, while a non-nominated site is not proof of absolute absence below every detection limit.

In-vitro nomination is not identical to editing frequency or biological consequence in a treated cell population or organism.

Connected domain graph

Typed dependencies preserve publication state.

Only independently canonical records receive public links and relation statements. Draft graph topology remains private.

mechanistic dependencycanonical

GUIDE-seq off-target detection

inbound connection · method

GUIDE-seq produces a nomination set that requires orthogonal confirmation and frequency measurement.

mechanistic dependencycanonical

CHANGE-seq off-target nomination

inbound connection · method

CHANGE-seq nominations require cellular confirmation under matched editor and delivery conditions.

Claim ledger

Every proposition keeps its own evidence state.

empirical-claimsingle-study

The cited study compares in-vitro CHANGE-seq nominations with cellular off-target activity and shows that genomic context and individual variation affect correspondence.

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.
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.

  1. Source 1 · Nature Biotechnology

    CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity

    Christopher R. Lazzarotto, Nhu T. Nguyen, J. A. Tangprasertchai, S. C. Malagon-Lopez, et al.

    Exact locator
    Abstract; Figures 1–6; Methods; datasets PRJNA625995 and GSE149295.
    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.
    Boundary
    In-vitro nomination is not identical to editing frequency or biological consequence in a treated cell population or organism.
    Rights basis
    citation with paraphrase · Maha paraphrases the source-level result and links to the version of record; no article passage is reproduced.
    Declared interests
    The article declares patent and company relationships involving genome-editing assays and therapeutics.