All matched case-control samples were tested on the same plates, but over the course of the study, samples were assayed on over 21 different plates per agent. To control for potential systematic error introduced by plate-toplate variation and to ensure that observed differences in OD are due to differential expression (cases or controls) and not experimental artifacts, data were normalized using the robust median normalization method which combines the within-plate and between-plates variance 41 using the following equation,