Similar organisms can reach people through different routes

Cases may share a source, belong to a broader circulating lineage, or have an indirect connection through unobserved cases. Sampling captures only part of that history.

The interpretation also depends on the pathogen, mutation patterns, sequencing quality, and analytic method.

Add the missing context

EvidenceQuestion it helps answer
Onset datesIs the timing compatible?
Exposure historiesIs there a shared route or setting?
Environmental samplesIs a plausible source detected?
Sampling coverageWhich links may be unobserved?

CDC's outbreak sequencing examples emphasize the combination of genomic and epidemiologic information.

Avoid a universal distance cutoff

A fixed number of genetic differences does not have the same meaning for every organism and investigation. The threshold and method need justification.

Absence of a match also needs context

Failure to find the organism in a suspected source may reflect limited or late sampling. It does not automatically exclude the source, just as a related sequence alone does not prove the entire causal chain.

Sequencing can greatly sharpen an investigation. Its value is strongest when it helps test a coherent explanation rather than replacing the work of establishing exposures, timing, and plausible transmission.