Remove unwanted variation retrieves unknown experimental designs

Remove unwanted variation (RUV) is an estimation and normalization system in which the underlying correlation structure of a multivariate dataset is estimated from negative control measurements, typically gene expression values, which are assumed to stay constant across experimental conditions. In this paper we derive the weight matrix which is estimated and incorporated into the generalized least squares estimates of RUV-inverse, and show that this weight matrix estimates the average covariance matrix across negative control measurements. RUV-inverse can thus be viewed as an estimation method adjusting for an unknown experimental design. We show that for a balanced incomplete block design (BIBD), RUV-inverse recovers intra- and interblock estimates of the relevant parameters and combines them as a weighted sum just like the best linear unbiased estimator (BLUE), except that the weights are globally estimated from the negative control measurements instead of being individually optimized to each measurement as in the classical, single measurement BIBD BLUE.     

Using Ordinary Least Squares Software to Compute Combined Intra-Interblock Estimates of Treatment Contrasts

Consideration is given to the computational aspects of the analysis of data from a comparative study, involving two or more treatments, in which the experimental units are arranged in b blocks. It may seem desirable, in making inferences about treatment contrasts, to carry out a combined intra-interblock analysis. Practitioners are sometimes reluctant to employ this analysis because of the computational requirements, which they regard as severe, and because they may not have ready access to directly applicable computer software. It is shown that by augmenting the actual data with b pseudo-observations, all of the computations can be accomplished efficiently, using only ordinary least squares software.     

Interblock information in multidimensional block designs

In many experimental situations, d-way heterogeneity among experimental units may be controlled through use of multiple blocking criteria. In some cases it is reasonable to regard some or all of the block effects as random. Then the model is mixed and observations within blocks are correlated. Very general estimators of treatment effects and their dispersion matrix with recovery of interblock information are provided. They apply to designs with d > 1 blocking criteria that may be crossed, nested, or a combination thereof. These general results may be specialized to provide analyses of new classes of MBD's or used directly for numerical analyses of designs in the general class, perhaps through use as the basis for very general computer programs. Estimation of variance components is discussed, and an example is provided to illustrate adaptation of the general results.