Microarray missing data imputation based on a set theoretic framework and biological knowledge

Gene expressions measured using microarrays usually suffer from the missing value problem. However, in many data analysis methods, a complete data matrix is required. Although existing missing value imputation algorithms have shown good performance to deal with missing values, they also have their limitations. For example, some algorithms have good performance only when strong local correlation exists in data while some provide the best estimate when data is dominated by global structure. In addition, these algorithms do not take into account any biological constraint in their imputation. In this paper, we propose a set theoretic framework based on projection onto convex sets (POCS) for missing data imputation. POCS allows us to incorporate different types of a priori knowledge about missing values into the estimation process. The main idea of POCS is to formulate every piece of prior knowledge into a corresponding convex set and then use a convergence-guaranteed iterative procedure to obtain a solution in the intersection of all these sets. In this work, we design several convex sets, taking into consideration the biological characteristic of the data: the first set mainly exploit the local correlation structure among genes in microarray data, while the second set captures the global correlation structure among arrays. The third set (actually a series of sets) exploits the biological phenomenon of synchronization loss in microarray experiments. In cyclic systems, synchronization loss is a common phenomenon and we construct a series of sets based on this phenomenon for our POCS imputation algorithm. Experiments show that our algorithm can achieve a significant reduction of error compared to the KNNimpute, SVDimpute and LSimpute methods

Challenges of Big Data Analysis

Big Data bring new opportunities to modern society and challenges to data scientists. On one hand, Big Data hold great promises for discovering subtle population patterns and heterogeneities that are not possible with small-scale data. On the other hand, the massive sample size and high dimensionality of Big Data introduce unique computational and statistical challenges, including scalability and storage bottleneck, noise accumulation, spurious correlation, incidental endogeneity, and measurement errors. These challenges are distinguished and require new computational and statistical paradigm. This article give overviews on the salient features of Big Data and how these features impact on paradigm change on statistical and computational methods as well as computing architectures. We also provide various new perspectives on the Big Data analysis and computation. In particular, we emphasis on the viability of the sparsest solution in high-confidence set and point out that exogeneous assumptions in most statistical methods for Big Data can not be validated due to incidental endogeneity. They can lead to wrong statistical inferences and consequently wrong scientific conclusions

Covariance Estimation in High Dimensions via Kronecker Product Expansions

This paper presents a new method for estimating high dimensional covariance matrices. The method, permuted rank-penalized least-squares (PRLS), is based on a Kronecker product series expansion of the true covariance matrix. Assuming an i.i.d. Gaussian random sample, we establish high dimensional rates of convergence to the true covariance as both the number of samples and the number of variables go to infinity. For covariance matrices of low separation rank, our results establish that PRLS has significantly faster convergence than the standard sample covariance matrix (SCM) estimator. The convergence rate captures a fundamental tradeoff between estimation error and approximation error, thus providing a scalable covariance estimation framework in terms of separation rank, similar to low rank approximation of covariance matrices. The MSE convergence rates generalize the high dimensional rates recently obtained for the ML Flip-flop algorithm for Kronecker product covariance estimation. We show that a class of block Toeplitz covariance matrices is approximatable by low separation rank and give bounds on the minimal separation rank $r$ that ensures a given level of bias. Simulations are presented to validate the theoretical bounds. As a real world application, we illustrate the utility of the proposed Kronecker covariance estimator for spatio-temporal linear least squares prediction of multivariate wind speed measurements.Comment: 47 pages, accepted to IEEE Transactions on Signal Processin

Measurement Error in Lasso: Impact and Correction

Regression with the lasso penalty is a popular tool for performing dimension reduction when the number of covariates is large. In many applications of the lasso, like in genomics, covariates are subject to measurement error. We study the impact of measurement error on linear regression with the lasso penalty, both analytically and in simulation experiments. A simple method of correction for measurement error in the lasso is then considered. In the large sample limit, the corrected lasso yields sign consistent covariate selection under conditions very similar to the lasso with perfect measurements, whereas the uncorrected lasso requires much more stringent conditions on the covariance structure of the data. Finally, we suggest methods to correct for measurement error in generalized linear models with the lasso penalty, which we study empirically in simulation experiments with logistic regression, and also apply to a classification problem with microarray data. We see that the corrected lasso selects less false positives than the standard lasso, at a similar level of true positives. The corrected lasso can therefore be used to obtain more conservative covariate selection in genomic analysis