Designs for two-colour microarray experiments

Summary.  Designs for two-colour microarray experiments can be viewed as block designs with two treatments per block. Explicit formulae for the A- and D-criteria are given for the case that the number of blocks is equal to the number of treatments. These show that the A- and D-optimality criteria conflict badly if there are 10 or more treatments. A similar analysis shows that designs with one or two extra blocks perform very much better, but again there is a conflict between the two optimality criteria for moderately large numbers of treatments. It is shown that this problem can be avoided by slightly increasing the number of blocks. The two colours that are used in each block effectively turn the block design into a row–column design. There is no need to use a design in which every treatment has each colour equally often: rather, an efficient row–column design should be used. For odd replication, it is recommended that the row–column design should be based on a bipartite graph, and it is proved that the optimal such design corresponds to an optimal block design for half the number of treatments. Efficient row–column designs are given for replications 3–6. It is shown how to adapt them for experiments in which some treatments have replication only 2.     

Constructions of efficiency-balanced designs

We present a number of methods of constructing efficiency-balanced binary block designs which are design patterns for simplification of statistical analysis. Furthermore, a method of construction of an efficiency-balanced block design with v+1 treatments from one with v treatments is generally characterized.     

Partially A-optimal blocked multi-factor designs

In this paper, we propose a partially A-optimal criterion for block designs where multiple factors are arranged. The number of levels of each factor is assumed to be arbitrary and unequal block sizes are allowed. A sufficient condition is derived for a design to be partially A-optimal among all feasible designs. Then the properties of the selected design and its relation with orthogonal arrays are studied. Methods of constructing designs satisfying the sufficient condition are also given.     

Connectedness of complete block designs under an interference model

We consider an experiment with fixed number of blocks, in which a response to a treatment can be affected by treatments from neighboring units. For such experiment the interference model with neighbor effects is studied. Under this model we study connectedness of binary complete block designs. Assuming the circular interference model with left-neighbor effects we give the condition for minimal number of blocks necessary to obtain connected design. For a specified class of binary, complete block designs, we show that all designs are connected. Further we present the sufficient and necessary conditions of connectedness of designs with arbitrary, fixed number of blocks.     

General upper bound for the number of blocks having a given number of treatments common with a given block

The purpose of this paper is systematically to derive the general upper bound for the number of blocks having a given number of treatments common with a given block of certain incomplete block designs. The approach adopted here is based on the spectral decomposition of N′N for the incidence matrix N of a design, where N' is the transpose of the matrix N. This approach will lead us to upper bounds for incomplete block designs, in particular for a large number of partially balanced incomplete block (PBIB) designs, which are not covered with the standard approach (Shah 1964, 1966), Kapadia (1966)) of using well known relations between blocks of the designs and their association schemes. Several results concerning block structure of block designs are also derived from the main theorem. Finally, further generalizations of the main theorem are discussed with some illustrations.     

Construction of (M,S)-optimal design for block size 3

(M,S)-optimal designs are constructed for block size three when the number of treatments is of the form 6t + 3.     

Optimum spacings of elementary treatment contrasts in symmetrical 2-factor pa block designs

The concept of optimum spacing of an arbitrary group of treatments was introduced by Sinha and Sinha (1969) in a study of the relative efficiencies of a group of block designs. In this paper, the optimum spacings of elementary treatment contrasts in a 2-factor symmetrical block design with Property A are studied using the A-optimality criterion. Conditions for optimum spacings are expressed in terms of the relative magnitudes of the efficiency factors.     

Bayes a-opttmal and efficient block designs for comparing test treatments with a standard treatment

A sufficient condition for the Bayes A-optimality of block designs when comparing a standard treatment with v test treatments is given by Majumdar. (In:Optimal Design and Analysis of Experiments, Y. Dodge, V. V. Fedorov and H. P. Wynn (Eds.), 15-27, North-Holland, 1988). The priors that he considers depend on a constant α ε [0, ∞), with α - 0 corresponding to no prior information at all. The given sufficient condition, consequently, also depends on a. Large families of optimal and highly efficient designs are only known for the case α - 0. We will show how some of the results for α - 0 can be extended to obtain large families of optimal and highly efficient designs for arbitrary values of α. In addition, these results are useful when considering design robustness against an improper choice of α.     

D-optimal block designs with at most six varieties

For given positive integers v, b, and k (all of them ≥2) a block design is a k × b array of the variety labels 1,…,v with blocks as columns. For the usual one-way heterogeneity model in standard form the problem is studied of finding a D-optimal block design for estimating the variety contrasts, when no balanced block design (BBD) exists. The paper presents solutions to this problem for v≤6. The results on D-optimality are derived from a graph-theoretic context. Block designs can be considered as multigraphs, and a block design is D-optimal iff its multigraph has greatest complexity (=number of spanning trees).     

Robust analysis of variance for a randomized block design

In this paper we study the asymptotic theory of M-estimates and their associated tests for a one-factor experiment in a randomized block design. In this case one natural asymptotic theory corresponds to leaving the number of treatments fixed and letting the number of blocks tend to infinity. The classic asymptotic theory of M-estimates does not apply here, because the number of parameters and the number of observations are of the same order. In this paper we prove the consistency and asymptotic normality of the estimators of the treatment effects. It turns out that the asymptotic covariance matrix of the treatment effects estimators differs from the one derived from the classic theory of M-estimates for the linear model with a fixed number of parameters. We also study a test for treatment effects derived from M-estimates and we compare by Monte Carlo simulation the efficiency of this test with respect to the F-test, the Friedman test and the test based on aligned ranks.     

Upper Bounds on the True Coverage of Bootstrap Percentile Type Confidence Intervals

A simple derivation of expected mean squares is given for the randomized (complete) block design, showing that “experimental error,” the error term for testing treatments, is comprised of three sources of variability: block by treatment interaction, within block plot-to-plot variability, and within experimental plot sampling variation. The approach could readily be extended to incorporate measurement error as a fourth component of experimental error.     

Fourth exact moment results for mrbp tests with two or three treatments

MRBP tests were proposed by Mielke and Iyer (1982) to analyze multivariate data for the randomized block design, based on permutation procedures. They obtained the first three exact moments of the MRBP test statistic to approximate its permutation distribution. Tracy and Khan (1991) derived its fourth exact moment, to obtain a better approximating distribution, when there are four or more treatments. In this paper we obtain the fourth exact moment when the number of treatments is less than four.     

Some sufficient conditions for the type 1 optimality of block designs

In this paper, we investigate the problem of determining block designs which are optimal under type 1 optimality criteria within various classes of designs having υ treatments arranged in b blocks of size k. The solutions to two optimization problems are given which are related to a general result obtained by Cheng (1978) and which are useful in this investigation. As one application of the solutions obtained, the definition of a regular graph design given in Mitchell and John (1977) is extended to that of a semi-regular graph design and some sufficient conditions are derived for the existence of a semi-regular graph design which is optimal under a given type 1 criterion. A result is also given which shows how the sufficient conditions derived can be used to establish the optimality under a specific type 1 criterion of some particular types of semi- regular graph designs having both equal and unequal numbers of replicates. Finally,some sufficient conditions are obtained for the dual of an A- or D-optimal design to be A- or D-optimal within an appropriate class of dual designs.     

On the E-optimality of complete block designs under a mixed interference model

In experiments in which the response to a treatment can be affected by other treatments, the interference model with neighbor effects is usually used. It is known that circular neighbor balanced designs (CNBDs) are universally optimal under such a model if the neighbor effects are fixed (Druilhet, 1999) or random (4 and 7). However, such designs cannot exist for every combination of design parameters. In the class of block designs with the same number of treatments as experimental units per block, a CNBD cannot exist if the number of blocks, b  , is equal to p(t−1)±1$p(t-1)\pm 1$, where p is a positive integer and t is the number of treatments. Filipiak et al. (2008) gave the structure of the left-neighboring matrix of E-optimal complete block designs with p  =1 under the model with fixed neighbor effects. The purpose of this paper is to generalize E-optimality results for designs with p∈N$p\in \mathbb{N}$ assuming random neighbor effects.     

Neighbor-Balanced Bipartite Block Designs

This article deals with the neighbor-balanced block design setting when there are two disjoint sets of treatments, one set consisting of test treatments and the other of control treatments. The interest here is to estimate the contrasts pertaining to test treatments vs. control treatments (with respect to direct and neighbors) with as high precision as possible. Some series of neighbor-balanced block designs for comparing a set of test treatments to a set of control treatments have been developed. The designs obtained are totally balanced in the sense that all the contrasts among test treatments for direct and neighbor effects are estimated with same variance and all the contrasts pertaining to test vs. control for direct and neighbor effects are estimated with the same variance.     

On the efficiency of some non-orthogonal split-plot×split-block designs with control treatments

Many split-plot×split-block (SPSB) type experiments used in agriculture, biochemistry or plant protection are designed to study new crop plant cultivars or chemical agents. In these experiments it is usually very important to compare test treatments with the so-called control treatments. It happens yet that experimental material is limited and it does not allow using a complete (orthogonal) SPSB design. In the paper we propose a non-orthogonal SPSB design for consideration. Two cases of the design are presented here, i.e. when its incompleteness is connected with a crossed treatment structure only or with a nested treatment structure only. It is assumed the factors' levels connected with the incompleteness of the design are split into two groups: a set of test treatments and a set of control treatments. The method of constructions involves applying augmented block designs for some factors' levels. In a modelling data obtained from such experiments the structure of experimental material and appropriate randomization scheme of the different kinds of units before they enter the experiment are taken into account. With respect to the analysis of the obtained randomization model the approach typical to the multistratum experiments with orthogonal block structure is adapted. The proposed statistical analysis of linear model obtained includes estimation of parameters, testing general and particular hypotheses defined by the (basic) treatment contrasts with special reference to the notion of general balance.     

Mixture experiments with process variables: d-optimal orthogonal experimental designs

Blending experiments with mixture in the presence of process variables are considered. We present an experimental design for quadratic (or linear) blending. The design in two orthogonal blocks is D-optimized in the case where there are no restrictions on the blending in two orthogonal blocks is presented when there are arbitrary restrictions on the blending components. The pair of orthogonal blocks can be used with and arbitrary number of process variables. The number of design points needed when different orthogonal blocks are used is usually smaller than when a single block is repeated at the various process variables levels.     

A-Optimal Block Designs with Additional Singly Replicated Treatments

Block designs to which have been added a number of singly-replicated treatments, known as secondary treatments, are particularly useful for experiments where only small amounts of material are available for some treatments, for example new plant varieties. The designs are of particular use in the microarray situation. Such designs are known as 'augmented designs'. This paper obtains the properties of these designs and shows that, with an equal number of secondary treatments in each block, the A-optimal design is obtained by using the A-optimal design for the original block design. It develops formulae for the variance of treatment comparisons, for both the primary and the secondary treatments. A number of examples are used to illustrate the results.     

RCBDs with a control

The randomized complete block designs, RCBDs, are among the most popular of block designs for comparing a set of experimental treatments. The question of this design's effectiveness when one of the treatments is a control is examined here. Optimality ranges are established for the RBCD in terms of the strength of interest in control comparisons. It is found that if the control treatment is of secondary interest, the RCBD, when not best, is typically near best. This is not so when comparisons with the control are of greater interest than those among the other treatments.     

Optimal Circular Block Designs for Neighbouring Competition Effects

Competition or interference occurs when the responses to treatments in experimental units are affected by the treatments in neighbouring units. This may contribute to variability in experimental results and lead to substantial losses in efficiency. The study of a competing situation needs designs in which the competing units appear in a predetermined pattern. This paper deals with optimality aspects of circular block designs for studying the competition among treatments applied to neighbouring experimental units. The model considered is a four-way classified model consisting of direct effect of the treatment applied to a particular plot, the effect of those treatments applied to the immediate left and right neighbouring units and the block effect. Conditions have been obtained for the block design to be universally optimal for estimating direct and neighbour effects. Some classes of balanced and strongly balanced complete block designs have been identified to be universally optimal for the estimation of direct, left and right neighbour effects and a list of universally optimal designs for v<20 and r<100 has been prepared.