Drug sensitivity prediction with high-dimensional mixture regression.

This paper proposes a mixture regression model-based method for drug sensitivity prediction. The proposed method explicitly addresses two fundamental issues in drug sensitivity prediction, namely, population heterogeneity and feature selection pertaining to each of the subpopulations. The mixture regression model is estimated using the imputation-conditional consistency algorithm, and the resulting estimator is consistent. This paper also proposes an average-BIC criterion for determining the number of components for the mixture regression model. The proposed method is applied to the CCLE dataset, and the numerical results indicate that the proposed method can make a drastic improvement over the existing ones, such as random forest, support vector regression, and regularized linear regression, in both drug sensitivity prediction and feature selection. The p-values for the comparisons in drug sensitivity prediction can reach the order O(10-8) or lower for the drugs with heterogeneous populations.

A Blockwise Consistency Method for Parameter Estimation of Complex Models.

The drastic improvement in data collection and acquisition technologies has enabled scientists to collect a great amount of data. With the growing dataset size, typically comes a growing complexity of data structures and of complex models to account for the data structures. How to estimate the parameters of complex models has put a great challenge on current statistical methods. This paper proposes a blockwise consistency approach as a potential solution to the problem, which works by iteratively finding consistent estimates for each block of parameters conditional on the current estimates of the parameters in other blocks. The blockwise consistency approach decomposes the high-dimensional parameter estimation problem into a series of lower-dimensional parameter estimation problems, which often have much simpler structures than the original problem and thus can be easily solved. Moreover, under the framework provided by the blockwise consistency approach, a variety of methods, such as Bayesian and frequentist methods, can be jointly used to achieve a consistent estimator for the original high-dimensional complex model. The blockwise consistency approach is illustrated using two high-dimensional problems, variable selection and multivariate regression. The results of both problems show that the blockwise consistency approach can provide drastic improvements over the existing methods. Extension of the blockwise consistency approach to many other complex models is straightforward.

A Split-and-Merge Approach for Singular Value Decomposition of Large-Scale Matrices.

We propose a new SVD algorithm based on the split-and- merge strategy, which possesses an embarrassingly parallel structure and thus can be efficiently implemented on a distributed or multicore machine. The new algorithm can also be implemented in serial for online eigen-analysis. The new algorithm is particularly suitable for big data problems: Its embarrassingly parallel structure renders it usable for feature screening, while this has been beyond the ability of the existing parallel SVD algorithms.