Comparing DNA fingerprints of infectious organisms

Genotypes of infectious organisms are becoming the foundation for epidemiol ogic studies of infectious disease. Central to the use of such data is a me ans for comparing genotypes. We develop methods for this purpose in the con text of DNA fingerprint genotyping of tuberculosis, but our approach is app licable to many fingerprint-based genotyping systems and/or organisms. Data available on replicate (laboratory) strains here reveal that (i) error in fingerprint band size is proportional to band size and (ii) errors are posi tively correlated within a fingerprint. Comparison (or matching) scores com puted to account for this error structure need to be "standardized" in orde r to properly rank the comparisons. We demonstrate the utility of using ext reme value distributions to effect such standardization. Several estimation issues for the extreme value parameters are discussed, including a lack of robustness of (approximate) maximum likelihood estimates. Interesting find ings to emerge from examination of quantiles of standardized matching score s include (i) formal significance is not attainable when querying a databas e for a given fingerprint pattern and (ii) maximal matching probabilities a re not necessarily monotonely decreasing with increasing numbers of fingerp rint bands.