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We consider large scale multiple testing for data that have locally clustered signals. With this structure, we apply techniques from changepoint analysis and propose a boundary detection algorithm so that the clustering information can be utilized. Consequently the precision of the multiple testing procedure is substantially improved. We study tests with independent as well as dependent p-values. Monte Carlo simulations suggest that the methods perform well with realistic sample sizes and show improved detection ability compared with competing methods. Our procedure is applied to a genome-wide association dataset of blood lipids. [ABSTRACT FROM AUTHOR]

Estimation of an unstructured covariance matrix is difficult because of its positive-definiteness constraint. This obstacle is removed by regressing each variable on its predecessors, so that estimation of a covariance matrix is shown to be equivalent to that of estimating a sequence of varying-coefficient and varying-order regression models. Our framework is similar to the use of increasing-order autoregressive models in approximating the covariance matrix or the spectrum of a stationary time series. As an illustration, we adopt Fan & Zhang's (2000) two-step estimation of functional linear models and propose nonparametric estimators of covariance matrices which are guaranteed to be positive definite. For parsimony a suitable order for the sequence of (auto)regression models is found using penalised likelihood criteria like AIC and BIC. Some asymptotic results for the local polynomial estimators of components of a covariance matrix are established. Two longitudinal datasets are analysed to illustrate the methodology. A simulation study reveals the advantage of the nonparametric covariance estimator over the sample covariance matrix for large covariance matrices. [ABSTRACT FROM AUTHOR]