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61.
Saddlepoint approximations in resampling methods   总被引:3,自引:0,他引:3  
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I describe in detail the intimately connected feature extraction and classifier development stages of the data-driven Statistical Classification Strategy (SCS) and compare them with current practice used in MR spectroscopy. We initially created the SCS for the analysis of MR and IR spectra of biofluids and tissues, and subsequently extended it to analyze biomedical data in general. I focus on explaining how to extract discriminatory spectral features and create robust classifiers that can reliably discriminate diseases and disease states. I discuss our approach to identifying features that retain spectral identity and provisionally relate these features, averaged subregions of the spectra, to specific chemical entities (“metabolites”). Particular emphasis is placed on describing the steps required to help create classifiers whose accuracy doesn’t deteriorate significantly when presented with new, unknown samples. A simple but powerful extension of the discovered features to detect metabolite-metabolite (feature-feature) interactions is also sketched. I contrast the advantages and disadvantages of using either spectral signatures or explicit metabolite concentrations derived from the spectra as sets of discriminatory features. At present, no clear-cut preference is obvious and more objective comparisons will be needed. Finally, I argue that clinical requirements and exigencies strongly suggest adopting a two-phase approach to diagnosis/prognosis. In the first phase the emphasis ought to be on providing as accurate a diagnosis as possible, without any attempt to identify “biomarkers.” That should be the goal of the second, research phase, with a view of providing prognosis on disease progression.  相似文献   
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Despite the importance of molecular phylogenetics, few of its assumptions have been tested with real data. It is commonly assumed that nonparametric bootstrap values are an underestimate of the actual support, Bayesian posterior probabilities are an overestimate of the actual support, and among-gene phylogenetic conflict is low. We directly tested these assumptions by using a well-supported yeast reference tree. We found that bootstrap values were not significantly different from accuracy. Bayesian support values were, however, significant overestimates of accuracy but still had low false-positive error rates (0% to 2.8%) at the highest values (>99%). Although we found evidence for a branch-length bias contributing to conflict, there was little evidence for widespread, strongly supported among-gene conflict from bootstraps. The results demonstrate that caution is warranted concerning conclusions of conflict based on the assumption of underestimation for support values in real data.  相似文献   
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The effects on insulin secretion from INS-1 cells of varying concentrations of the sulfonylurea glyburide and the PDE3 inhibitor milrinone, separately and in combination were measured. Over a range of concentrations the effects of the two drugs in combination were more than additive. A response surface model was fit to the data and was found to describe the data well. From this model, it was apparent that a significant synergistic effect upon insulin secretion existed over a wide range of combinations of the two drugs.  相似文献   
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Chen SX  Yip PS  Zhou Y 《Biometrics》2002,58(2):263-269
This article considers using sequential procedures to determine the amount of survey effort required in a line transect survey in order to achieve a certain precision level in estimating the abundance of a biological population. Sequential procedures are constructed for both parametric and nonparametric animal abundance estimators. The criterion used to derive the stopping rules is the width of confidence intervals for the animal abundance. For each estimator considered, we develop stopping rules based on the asymptotic distributions and the bootstrap. A sequential analysis on an aerial survey of the southern bluefin tuna indicates substantial saving of survey effort can be made by employment of the proposed sequential procedures. This savings of survey effort is also observed in a simulation study designed to evaluate the empirical performance of the proposed sequential procedures.  相似文献   
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Stimulated by the rapid progress in developmental genetics, recent approaches to evolutionary theory focus on the interface function of developmental processes in the study of genotype-phenotype mapping. From this viewpoint, the main result of the present analysis is that the expression patterns of developmental control genes are reflected in the infraspecific correlation patterns of phenotypic characters in the adult stage. The study is based on 42 logarithmically scaled skeletal measurements of two avian clades, finches (43 species, n = 313) and pigeons (27 species, n = 219). First, for each clade an “observed correlation matrix” was calculated by computing a bias-reduced pooled-species correlation matrix based on the clade-specific pooled within-species variance-covariance matrix between measurements. Second, the expression domains of diverse developmental control genes, that is, Hox, Msx, Pax, Mhox, Shh, Bmp, and Gdf, in characters were represented by “theoretical matrices.” Finally, the observed and the theoretical matrices were compared by Mantel's test to test hypotheses about pattern similarities between phenotypic correlations and the expression of developmental control genes. Seventeen percent of the single matrix comparisons revealed significant (P ≤ 0.05) pattern correspondences in finches, whereas 63% were significant in pigeons. The multiple comparisons revealed correspondences at the highest significance level (P ≤ 0.001) in both clades and disclosed that 15% of the observed matrix patterns are explained in finches versus 22% in pigeons. Presumably, as finches have less pronounced correspondences between gene expression and phenotypic correlation, they are more derived than pigeons. Out of the significant single matrix comparisons, four correspondences are common to both clades: one of them is connected with the Gdf gene expression concerning limb length relations and also harmonizes with the dominant pattern within the infraspecific correlation matrices. The general implication is that the significant correspondences detected here between observed and theoretical matrices are based on a correspondence between phenotypic and genetic modules. Because the phenotypic modules are potential candidates for a direct impact of selection, the important role of genotype-phenotype mapping in molding the body plan becomes apparent.  相似文献   
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