When does a negative assay exclude a finite target count? Sharp false-exclusion bounds for native-reference reporting rules
Abstract
A negative readout need not exclude targets in the original specimen when extraction failures are shared across targets and splitting consumes material. We study a finite, well-mixed specimen with conditionally independent target paths and arbitrary dependence between two preparation recoveries. A sharp moment bound reduces the all-negative probability to four recovery states. An explicit reporting rule accepts each of independent native-reference pairs whenever at least one reference is recovered, and issues a count-exclusion certificate only if the future assay is also negative. For balanced effective fractions , the exact worst-case probability of a false certificate is , where has a closed two-branch formula; no equality of marginal recovery means is needed, and an explicit source attains the value. We then quantify four things that a reporting rule must survive. Reusing one calibration across independent specimens has an exact familywise value with an irreducible floor , so a five percent familywise level is unreachable for two specimens in the worked design however many references are bought. Replacing the exactly-one reference input by Poisson loading of mean leaves the guarantee intact for , has a closed sharp value under an explicit rational criterion, and in general reduces to a one-dimensional concave-envelope problem; heavy loading destroys the guarantee outright. An event-specific allowance for observation-law mismatch replaces a product-coupling bound that was an order of magnitude looser. Spurious control positives admit an exact reduction to the same scalar problem, and the resulting specificity budget — a pair false-positive rate below about — is the binding practical constraint. Finally, imposing equal means and nonnegative covariance moves the feasibility threshold from to , which makes an otherwise impossible exclusion attainable. The central chain and the new batch, false positive and Poisson results are mechanized in Lean 4; biological transport remains an experimental premise.