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K Dobbin

Publications and source records attributed to K Dobbin.

4 recordsLinked to original sources
PubMed2003

Statistical design of reverse dye microarrays.

MOTIVATION: In cDNA microarray experiments all samples are labelled with either Cy3 dye or Cy5 dye. Certain genes exhibit dye bias-a tendency to bind more efficiently to one of the dyes. The common reference design avoids the problem of dye bias by running all arrays 'forward', so that the samples being compared are always labelled with the same dye. But comparison of samples labelled with different dyes is sometimes of interest. In these situations, it is necessary to run some arrays 'reverse'-with the dye labelling reversed-in order to correct for the dye bias. The design of these experiments will impact one's ability to identify genes that are differentially expressed in different tissues or conditions. We address the design issue of how many specimens are needed, how many forward and reverse labelled arrays to perform, and how to optimally assign Cy3 and Cy5 labels to the specimens. RESULTS: We consider three types of experiments for which some reverse labelling is needed: paired samples, samples from two predefined groups, and reference design data when comparison with the reference is of interest. We present simple probability models for the data, derive optimal estimators for relative gene expression, and compare the efficiency of the estimators for a range of designs. In each case, we present the optimal design and sample size formulas. We show that reverse labelling of individual arrays is generally not required.

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PubMed2002

Comparison of microarray designs for class comparison and class discovery.

MOTIVATION: Two-color microarray experiments in which an aliquot derived from a common RNA sample is placed on each array are called reference designs. Traditionally, microarray experiments have used reference designs, but designs without a reference have recently been proposed as alternatives. RESULTS: We develop a statistical model that distinguishes the different levels of variation typically present in cancer data, including biological variation among RNA samples, experimental error and variation attributable to phenotype. Within the context of this model, we examine the reference design and two designs which do not use a reference, the balanced block design and the loop design, focusing particularly on efficiency of estimates and the performance of cluster analysis. We calculate the relative efficiency of designs when there are a fixed number of arrays available, and when there are a fixed number of samples available. Monte Carlo simulation is used to compare the designs when the objective is class discovery based on cluster analysis of the samples. The number of discrepancies between the estimated clusters and the true clusters were significantly smaller for the reference design than for the loop design. The efficiency of the reference design relative to the loop and block designs depends on the relation between inter- and intra-sample variance. These results suggest that if cluster analysis is a major goal of the experiment, then a reference design is preferable. If identification of differentially expressed genes is the main concern, then design selection may involve a consideration of several factors.

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PubMed1992

Pulmonary artery pressure measurement in patients with elevated pressures: effect of backrest elevation and method of measurement.

OBJECTIVE: To determine whether pulmonary artery pressure measurement is accurate if the head of the bed is elevated; to compare the end-expiratory graphic recording and digital monitor methods for pulmonary artery pressure measurement; to determine whether either mean arterial pressure or mixed venous oxygen saturation changes during backrest elevation. DESIGN: Nonrandomized clinical trial. SETTING: A six-bed cardiac surgical intensive care unit of a 540-bed federal facility. POPULATION: Twenty-five postoperative cardiac surgical patients with elevated pulmonary artery pressures (systolic higher than 35 mm Hg). INTERVENTIONS: In supine patients pulmonary artery pressures were measured at each of the following backrest elevations: 0, 20, 30, 45 and again at 0 degrees. Measurements were obtained once during mechanical ventilation and once during normal breathing after extubation. MAIN OUTCOME MEASURES: End-expiratory graphic recording of pulmonary artery pressures; digital monitor values of pulmonary artery pressures; mean arterial pressure; and mixed venous oxygen saturation. RESULTS: No statistical difference was found in pulmonary artery pressures measured at each of the backrest elevations during mechanical ventilation or normal breathing after extubation. Pulmonary artery diastolic and pulmonary capillary wedge pressures obtained with the digital monitor method were significantly lower than the end expiratory graphic recording method during normal breathing after extubation but not during mechanical ventilation. No changes in mean arterial pressure or mixed venous oxygen saturation occurred during backrest elevation. CONCLUSIONS: These results show that pulmonary artery pressures can be measured accurately with the head of the bed in an elevated position. The data indicate that obtaining pulmonary artery pressure measurements from the digital display of the bedside monitor is accurate when respiratory wave form fluctuations are minimal but may lead to inaccurate values with prominent respiratory fluctuations. Further research is needed to validate this finding in different patient populations and with other models of monitoring equipment.

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