Conceptual Aspects of Large Meta-Analyses with Publicly Available Microarray Data: A Case Study in Oncology

Large public repositories of microarray experiments offer an abundance of biological data. It is of interest to use and to combine the available material to create new biological information and to develop a broader view on biological phenomena

Model selection through sparse maximum likelihood estimation

personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. To copy otherwise, to republish, to post on servers or to redistribute to lists, requires prior specific permission

Sparse covariance selection via robust maximum likelihood estimation

We address a problem of covariance selection, where we seek a trade-off between a high likelihood against the number of non-zero elements in the inverse covariance matrix. We solve a maximum likelihood problem with a penalty term given by the sum of absolute values of the elements of the inverse covariance matrix, and allow for imposing bounds on the condition number of the solution. The problem is directly amenable to now standard interiorpoint algorithms for convex optimization, but remains challenging due to its size. We first give some results on the theoretical computational complexity of the problem, by showing that a recent methodology for non-smooth convex optimization due to Nesterov can be applied to this problem, to greatly improve on the complexity estimate given by interior-point algorithms. We then examine two practical algorithms aimed at solving large-scale, noisy (hence dense) instances: one is based on a block-coordinate descent approach, where columns and rows are updated sequentially, another applies a dual version of Nesterov’s method.

First-order methods for sparse covariance selection

Abstract. Given a sample covariance matrix, we solve a maximum likelihood problem penalized by the number of nonzero coefficients in the inverse covariance matrix. Our objective is to find a sparse representation of the sample data and to highlight conditional independence relationships between the sample variables. We first formulate a convex relaxation of this combinatorial problem, we then detail two efficient first-order algorithms with low memory requirements to solve large-scale, dense problem instances

Convex optimization techniques for fitting sparse gaussian graphical models

We consider the problem of fitting a large-scale covariance matrix to multivariate Gaussian data in such a way that the inverse is sparse, thus providing model selection. Beginning with a dense empirical covariance matrix, we solve a maximum likelihood problem with an l1-norm penalty term added to encourage sparsity in the inverse. For models with tens of nodes, the resulting problem can be solved using standard interior-point algorithms for convex optimization, but these methods scale poorly with problem size. We present two new algorithms aimed at solving problems with a thousand nodes. The first, based on Nesterov’s first-order algorithm, yields a rigorous complexity estimate for the problem, with a much better dependence on problem size than interior-point methods. Our second algorithm uses block coordinate descent, updating row/columns of the covariance matrix sequentially. Experiments with genomic data show that our method is able to uncover biologically interpretable connections among genes. 1