We propose a low-overhead sampling infrastructure for gathering information from the executions experienced by a program 's user community. Several example applications illustrate ways to use sampled instrumentation to isolate bugs. Assertion-dense code can be transformed to share the cost of assertions among many users. Lacking assertions, broad guesses can be made about predicates that predict program errors and a process of elimination used to whittle these down to the true bug. Finally, even for non-deterministic bugs such as memory corruption, statistical modeling based on logistic regression allows us to identify program behaviors that are strongly correlated with failure and are therefore likely places to look for the error.

Summary. We propose the elastic net, a new regularization and variable selection method. Real world data and a simulation study show that the elastic net often outperforms the lasso, while enjoying a similar sparsity of representation. In addition, the elastic net encourages a grouping effect, where strongly correlated predictors tend to be in or out of the model together.The elastic net is particularly useful when the number of predictors (p) is much bigger than the number of observations (n). By contrast, the lasso is not a very satisfactory variable selection method in the p n case. An algorithm called LARS-EN is proposed for computing elastic net regularization paths efficiently, much like algorithm LARS does for the lasso.

Principal component analysis (PCA) is widely used in data processing and dimensionality reduction. However, PCA su#ers from the fact that each principal component is a linear combination of all the original variables, thus it is often di#cult to interpret the results. We introduce a new method called sparse principal component analysis (SPCA) using the lasso (elastic net) to produce modified principal components with sparse loadings. We show that PCA can be formulated as a regression-type optimization problem, then sparse loadings are obtained by imposing the lasso (elastic net) constraint on the regression coe#cients. E#cient algorithms are proposed to realize SPCA for both regular multivariate data and gene expression arrays. We also give a new formula to compute the total variance of modified principal components. As illustrations, SPCA is applied to real and simulated data, and the results are encouraging.

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The lasso (Tibshirani 1996) penalizes a least squares regression by the sum of the absolute values (L1 norm) of the coefficients. The form of this penalty encourages sparse solutions, that is, having many coefficients equal to zero. Here we propose the “fused lasso”, a generalization of the lasso designed for problems with features that can be ordered in some meaningful way. The fused lasso penalizes both the L1 norm of the coefficients and their successive differences. Thus it encourages both sparsity

We propose a representation for gene expression data called conserved gene expression motifs or xmotifs. A gene's expression level is conserved across a set of samples if the gene is expressed with the same abundance in all the samples. A conserved gene expression motif is a subset of genes that is simultaneously conserved across a subset of samples.

Motivation: Two practical realities constrain the analysis of microarray data, mass spectra from proteomics, and biomedical infrared or magnetic resonance spectra. One is the ‘curse of dimensionality’: the number of features characterizing these data is in the thousands or tens of thousands. The other is the ‘curse of dataset sparsity’: the number of samples is limited. The consequences of these two curses are far-reaching when such data are used to classify the presence or absence of disease. Results: Using very simple classifiers, we show for several publicly available microarray and proteomics datasets how these curses influence classification outcomes. In particular, even if the sample per feature ratio is increased to the recommended 5–10 by feature extraction/reduction methods, dataset sparsity can render any classification result statistically suspect. In addition, several ‘optimal’ feature sets are typically identifiable for sparse datasets, all producing perfect classification results, both for the training and independent validation sets. This non-uniqueness leads to interpretational difficulties and casts doubt on the biological relevance of any of these ‘optimal’ feature sets. We suggest an approach to assess the relative quality of apparently equally good classifiers.

Abstract. We propose a new method for class prediction in DNA microarray studies based on an enhancement of the nearest prototype classifier. Our technique uses “shrunken ” centroids as prototypes for each class to identify the subsets of the genes that best characterize each class. The method is general and can be applied to other high-dimensional classification problems. The method is illustrated on data from two gene expression studies: lymphoma and cancer cell lines. Key words and phrases: Sample classification, gene expression arrays. 1.

In regression problems where the number of predictors greatly exceeds the number of observations, conventional regression techniques may produce unsatisfactory results. We describe a technique called supervised principal components that can be applied to this type of problem. Supervised principal components is similar to conventional principal components analysis except that it uses a subset of the predictors selected based on their association with the outcome. Supervised principal components can be applied to regression and generalized regression problems, such as survival analysis. It compares favorably to other techniques for this type of problem, and can also account for the effects of other covariates and help identify which predictor variables are most important. We also provide asymptotic consistency results to help support our empirical findings. These methods could become important tools for DNA microarray data, where they may be used to more accurately diagnose and treat cancer. KEY WORDS: Gene expression; Microarray; Regression; Survival analysis. 1.

This paper discusses the problem of identifying differentially expressed groups of genes from a microarray experiment. The groups of genes are externally defined, for example, sets of gene pathways derived from biological databases. Our starting point is the interesting Gene Set Enrichment Analysis (GSEA) procedure of Subramanian et al. (2005). We study the problem in some generality and propose two potential improvements to GSEA: the maxmean statistic for summarizing gene-sets, and restandardization for more accurate inferences. We discuss a variety of examples and extensions, including the use of gene-set scores for class predictions. We also describe a new R language package GSA that implements our ideas. 1