Limiting dilution assays for the determination of immunocompetent cell frequencies. III. Validity tests for the single-hit Poisson model.
A statistical method was developed to test the validity of the single-hit Poisson model in limiting dilution assays used to determine immunocompetent cell frequencies. Principles of bioassay, validity tests, and the distinction between model-discrimination experiments and parameter-estimation assays are reviewed in the Introduction. The new test derived and then demonstrated with previously published data is intended to be used for parameter-estimation assays based upon the single-hit Poisson model. It is a family of related chi 2, t, and F tests for deviations from zero of the slopes of weighted least squares regression plots. These plots regress the logarithms of single-dose estimates fi of the frequency phi on the total cell doses lambda i and fi on the total cell dose reciprocals 1/lambda i, that is, Yi = ln fi on Xi = lambda i and Yi = fi on Xi = 1/lambda i. The test discriminates against alternative models with multiple-hit/target response-generation processes, a variable number (dose-dependent) of false negatives, and a constant number (dose-independent) of false positives. Its purpose as a test for parameter-estimation assays, though, is to detect deviations from the single-hit Poisson model and not to select one of these alternative models. Tests for model-discrimination experiments to select or 'prove' an unknown alternative model are considered in light of relevant literature reviewed in the Discussion.
D000818:Animals; D002452:Cell Count; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods*; D004306:Dose-Response Relationship, Immunologic; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008954:Models, Biological; D013154:Spleen / Q000166:cytology; D013223:Statistics as Topic; D013234:Stem Cells / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology