[The use of analysis of variance in studying population morbidity].
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BACKGROUND: DNA microarrays open up a new horizon for studying the genetic determinants of disease. The high throughput nature of these arrays creates an enormous wealth of information, but also poses a challenge to data analysis. Inferential problems become even more pronounced as experimental designs used to collect data become more complex. An important example is multigroup data collected over different experimental groups, such as data collected from distinct stages of a disease process. We have developed a method specifically addressing these issues termed Bayesian ANOVA for microarrays (BAM). The BAM approach uses a special inferential regularization known as spike-and-slab shrinkage that provides an optimal balance between total false detections and total false non-detections. This translates into more reproducible differential calls. Spike and slab shrinkage is a form of regularization achieved by using information across all genes and groups simultaneously. RESULTS: BAMarray is a graphically oriented Java-based software package that implements the BAM method for detecting differentially expressing genes in multigroup microarray experiments (up to 256 experimental groups can be analyzed). Drop-down menus allow the user to easily select between different models and to choose various run options. BAMarraycan also be operated in a fully automated mode with preselected run options. Tuning parameters have been preset at theoretically optimal values freeing the user from such specifications. BAMarray provides estimates for gene differential effects and automatically estimates data adaptive, optimal cutoff values for classifying genes into biological patterns of differential activity across experimental groups. A graphical suite is a core feature of the product and includes diagnostic plots for assessing model assumptions and interactive plots that enable tracking of prespecified gene lists to study such things as biological pathway perturbations. The user can zoom in and lasso genes of interest that can then be saved for downstream analyses. CONCLUSION: BAMarray is user friendly platform independent software that effectively and efficiently implements the BAM methodology. Classifying patterns of differential activity is greatly facilitated by a data adaptive cutoff rule and a graphical suite. BAMarray is licensed software freely available to academic institutions. More information can be found at http://www.bamarray.com.
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Variance analysis, an accounting technique, is applied to an eight-component model of hospital costs to determine the contribution each component makes to cost increases. The method is illustrated by application to data on total costs from 1950 to 1973 for all U.S. nongovernmental not-for-profit short-term general hospitals. The costs of a single hospital are analyzed and compared to the group costs. The potential uses and limitations of the method as a planning and research tool are discussed.
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Researchers often test the wrong statistical hypothesis in evaluating their experiments, thereby drawing wrong conclusions. Examples of this are given. In addition, data containing correlations among subjects require a different form of statistical analysis than do data involving independent observations. Errors that can result from an incorrect analysis are illustrated.
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A definition is proposed for the interquarter ratio of markers of inflammation in the bovine mammary gland which in contrast to present measurement procedures has well-defined distributional properties and thus facilitates statistical analysis. Our proposal of an interquarter ratio is equally applicable to evaluation of both single and multi-sample experiments. Finally, we define a new index for diagnosis of subclinical mastitis at the cow level, the interquarter variation, which assesses the degree of dispersion of the four quarter levels for values of any continuous inflammatory marker.
To study bone histomorphometry reproducibility in normal subjects, we performed during orthopedic surgery bone biopsies in 16 postmenopausal women. Each woman had four bone biopsies, two at the usual site in the iliac crest, one on the left and one on the right side, and two other biopsies just behind the usual site, one at each side. We performed measurements of trabecular bone volume, relative osteoid volume, osteoid surfaces, osteoclastic resorption surfaces and calcification front. The average values of the 16 patients were compared, on the one hand, two by two, by a student test, and on the other hand, by a variance analysis. By these two methods the results showed no significant difference between the average values of the 16 patients at each location for any of the histomorphometric parameters studied. However, there was a location variation which was estimated by the intra-individual variation for a given patient. On the other hand, we calculated from the variance analysis the location variance for a group of 10 to 100 patients. In any case all the parameters had a location variation which was high for osteoclastic resorption surfaces and relative osteoid volume when expressed in % of the absolute value of these parameters. The variation of the trabecular bone volume was 0--46. 15% (95% confident limit interval) in a single patient and the hypothetical value of the location variation was 41.6% for a group of 10 patients and 13.0% for a group of 100 patients.