Protocol Table of Contents
Design and Methods - Multiple Domain Screen - CCMS
Test protocol - Eight-week-old mice will be placed in individual CCMS cages between 11:30 a.m. and 1:00 p.m. on Day 1 of a 3-day test period. A 3-day test period allows examination of response to a novel environment from data collected on Day 1 and leaves two additional days for diurnal patterns to be established.
Animals testing negative on the 8-week screen will be re-tested at one year of age to identify mutations that lead to moderate and/or late-onset obesity. At this time the mice will also be assessed for body weight (BW) and body-mass index. Mice found deviant by the same criteria as above will undergo heritability testing.
Algorithm development - Although simply examining data from each mouse for values that lie greater than 3 s.d. outside of the control mean will detect potential mutants, this approach does not fully exploit the CCMS data set. We are currently developing a statistical algorithm for mutant detection that can incorporate multiple measures. Briefly, the algorithm first "trains" on a data set from normal mice then computes the Mahalanobis distance (Krzanowski, 1988) between subsequent individual mice and the training set. If this distance is "too" large the mouse is flagged as an outlier. The cutoff distance for flagging can be adjusted for a desired rate of false positives. The algorithm presently incorporates only 3 CCMS measures but will be expanded to incorporate additional parameters.
