Sparse integrative clustering of multiple omics data sets

High resolution microarrays and second-generation sequencing platforms are powerful tools to investigate genome-wide alterations in DNA copy number, methylation and gene expression associated with a disease. An integrated genomic profiling approach measures multiple omics data types simultaneously in the same set of biological samples. Such approach renders an integrated data resolution that would not be available with any single data type. In this study, we use penalized latent variable regression methods for joint modeling of multiple omics data types to identify common latent variables that can be used to cluster patient samples into biologically and clinically relevant disease subtypes. We consider lasso [J. Roy. Statist. Soc. Ser. B 58 (1996) 267-288], elastic net [J. R. Stat. Soc. Ser. B Stat. Methodol. 67 (2005) 301-320] and fused lasso [J. R. Stat. Soc. Ser. B Stat. Methodol. 67 (2005) 91-108] methods to induce sparsity in the coefficient vectors, revealing important genomic features that have significant contributions to the latent variables. An iterative ridge regression is used to compute the sparse coefficient vectors. In model selection, a uniform design [Monographs on Statistics and Applied Probability (1994) Chapman & Hall] is used to seek "experimental" points that scattered uniformly across the search domain for efficient sampling of tuning parameter combinations. We compared our method to sparse singular value decomposition (SVD) and penalized Gaussian mixture model (GMM) using both real and simulated data sets. The proposed method is applied to integrate genomic, epigenomic and transcriptomic data for subtype analysis in breast and lung cancer data sets.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS578 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Dimensionality Reduction for k-Means Clustering and Low Rank Approximation

We show how to approximate a data matrix $\mathbf{A}$ with a much smaller sketch $\mathbf{\tilde A}$ that can be used to solve a general class of constrained k-rank approximation problems to within $(1+\epsilon)$ error. Importantly, this class of problems includes $k$-means clustering and unconstrained low rank approximation (i.e. principal component analysis). By reducing data points to just $O(k)$ dimensions, our methods generically accelerate any exact, approximate, or heuristic algorithm for these ubiquitous problems. For $k$-means dimensionality reduction, we provide $(1+\epsilon)$ relative error results for many common sketching techniques, including random row projection, column selection, and approximate SVD. For approximate principal component analysis, we give a simple alternative to known algorithms that has applications in the streaming setting. Additionally, we extend recent work on column-based matrix reconstruction, giving column subsets that not only `cover' a good subspace for \bv{A}, but can be used directly to compute this subspace. Finally, for $k$-means clustering, we show how to achieve a $(9+\epsilon)$ approximation by Johnson-Lindenstrauss projecting data points to just $O(\log k/\epsilon^2)$ dimensions. This gives the first result that leverages the specific structure of $k$-means to achieve dimension independent of input size and sublinear in $k$