TY - JOUR
T1 - A Simple Formula for Obtaining Markedly Improved Mutation Rate Estimates
JF - Genetics
JO - Genetics
SP - 1773
LP - 1778
DO - 10.1534/genetics.108.091777
VL - 180
IS - 3
AU - Gerrish, Philip
Y1 - 2008/11/01
UR - http://www.genetics.org/content/180/3/1773.abstract
N2 - In previous work by M. E. Jones and colleagues, it was shown that mutation rate estimates can be improved and corresponding confidence intervals tightened by following a very easy modification of the standard fluctuation assay: cultures are grown to a larger-than-usual final density, and mutants are screened for in only a fraction of the culture. Surprisingly, this very promising development has received limited attention, perhaps because there has been no efficient way to generate the predicted mutant distribution to obtain non-moment-based estimates of the mutation rate. Here, the improved fluctuation assay discovered by Jones and colleagues is made amenable to quantile-based, likelihood, and other Bayesian methods by a simple recursion formula that efficiently generates the entire mutant distribution after growth and dilution. This formula makes possible a further protocol improvement: grow cultures as large as is experimentally possible and severely dilute before plating to obtain easily countable numbers of mutants. A preliminary look at likelihood surfaces suggests that this easy protocol adjustment gives markedly improved mutation rate estimates and confidence intervals.
ER -