published-canonicalmethodmaha-epistemic/1.0

CHANGE-seq off-target nomination

An in-vitro circularized-genomic-DNA assay for high-throughput nomination of Cas9 cleavage activity. 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

An in-vitro circularized-genomic-DNA assay for high-throughput nomination of Cas9 cleavage activity.

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:change-seq-off-target-nomination

What remains a separate question

In-vitro cleavage nomination does not directly measure editing frequency or consequence in the intended cell product or organism.

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.

strategic dependencycanonical

In-vitro versus in-vivo evidence

inbound connection · comparison

In-vitro nomination supports but does not replace cellular and organism measurements.

Claim ledger

Every proposition keeps its own evidence state.

empirical-claimsingle-study

The cited study applies CHANGE-seq across many guides and compares nominations with cellular activity and genomic context.

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
In-vitro cleavage nomination does not directly measure editing frequency or consequence in the intended cell product or organism.
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.