Penalized Clustering of Large Scale Functional Data with Multiple Covariates

In this article, we propose a penalized clustering method for large scale data with multiple covariates through a functional data approach. In the proposed method, responses and covariates are linked together through nonparametric multivariate functions (fixed effects), which have great flexibility in modeling a variety of function features, such as jump points, branching, and periodicity. Functional ANOVA is employed to further decompose multivariate functions in a reproducing kernel Hilbert space and provide associated notions of main effect and interaction. Parsimonious random effects are used to capture various correlation structures. The mixed-effect models are nested under a general mixture model, in which the heterogeneity of functional data is characterized. We propose a penalized Henderson's likelihood approach for model-fitting and design a rejection-controlled EM algorithm for the estimation. Our method selects smoothing parameters through generalized cross-validation. Furthermore, the Bayesian confidence intervals are used to measure the clustering uncertainty. Simulation studies and real-data examples are presented to investigate the empirical performance of the proposed method. Open-source code is available in the R package MFDA

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