High-throughput microbial sequencing techniques, such as targeted amplicon-based and metagenomic profiling, provide low-cost genomic survey data of microbial communities in their natural environment, ranging from marine ecosystems to host-associated habitats. While standard microbiome profiling data can provide sparse relative abundances of operational taxonomic units or genes, recent advances in experimental protocols give a more quantitative picture of microbial communities by pairing sequencing-based techniques with orthogonal measurements of microbial cell counts from the same sample. These tandem measurements provide absolute microbial count data albeit with a large excess of zeros due to limited sequencing depth. In this contribution we consider the fundamental statistical problem of estimating correlations and partial correlations from such quantitative microbiome data. To this end, we propose a semi-parametric rank-based approach to correlation estimation that can naturally deal with the excess zeros in the data. Combining this estimator with sparse graphical modeling techniques leads to the Semi-Parametric Rank-based approach for INference in Graphical model (SPRING). SPRING enables inference of statistical microbial association networks from quantitative microbiome data which can serve as high-level statistical summary of the underlying microbial ecosystem and can provide testable hypotheses for functional species-species interactions. Due to the absence of verified microbial associations we also introduce a novel quantitative microbiome data generation mechanism which mimics empirical marginal distributions of measured count data while simultaneously allowing user-specified dependencies among the variables. SPRING shows superior network recovery performance on a wide range of realistic benchmark problems with varying network topologies and is robust to misspecifications of the total cell count estimate. To highlight SPRING's broad applicability we infer taxon-taxon associations from the American Gut Project data and genus-genus associations from a recent quantitative gut microbiome dataset. We believe that, as quantitative microbiome profiling data will become increasingly available, the semi-parametric estimators for correlation and partial correlation estimation introduced here provide an important tool for reliable statistical analysis of quantitative microbiome data.

High-throughput microbial sequencing techniques, such as targeted amplicon-based and metagenomic profiling, provide low-cost genomic survey data of microbial communities in their natural environment, ranging from marine ecosystems to host-associated habitats. While standard microbiome profiling data can provide sparse relative abundances of operational taxonomic units or genes, recent advances in experimental protocols give a more quantitative picture of microbial communities by pairing sequencingbased techniques with orthogonal measurements of microbial cell counts from the same sample. These tandem measurements provide absolute microbial count data albeit with a large excess of zeros due to limited sequencing depth. In this contribution we consider the fundamental statistical problem of estimating correlations and partial correlations from such quantitative microbiome data. To this end, we propose a semi-parametric rank-based approach to correlation estimation that can naturally deal with the excess zeros in the data. Combining this estimator with sparse graphical modeling techniques leads to the Semi-Parametric Rank-based approach for INference in Graphical model (SPRING). SPRING enables inference of statistical microbial association networks from quantitative microbiome data which can serve as high-level statistical summary of the underlying microbial ecosystem and can provide testable hypotheses for functional species-species interactions. Due to the absence of verified microbial associations we also introduce a novel quantitative microbiome data generation mechanism which mimics empirical marginal distributions of measured count data while simultaneously allowing user-specified dependencies among the variables. SPRING shows superior network recovery performance on a wide range of realistic benchmark problems with varying network topologies and is robust to misspecifications of the total cell count estimate. To highlight SPRING's broad applicability we infer taxon-taxon associations from the American Gut Project data and genus-genus associations from a recent quantitative gut microbiome dataset. We believe that, as quantitative microbiome profiling data will become increasingly available, the semi-parametric estimators for correlation and partial correlation estimation introduced here provide an important tool for reliable statistical analysis of quantitative microbiome data.

The increased availability of multi-view data (data on the same samples from multiple sources) has led to strong interest in models based on low-rank matrix factorizations. These models represent each data view via shared and individual components, and have been successfully applied for exploratory dimension reduction, association analysis between the views, and consensus clustering. Despite these advances, there remain challenges in modeling partially-shared components and identifying the number of components of each type (shared/ partially-shared/individual). We formulate a novel linked component model that directly incorporates partially-shared structures. We call this model SLIDE for Structural Learning and Integrative DEcomposition of multi-view data. The proposed model-fitting and selection techniques allow for joint identification of the number of components of each type, in contrast to existing sequential approaches. In our empirical studies, SLIDE demonstrates excellent performance in both signal estimation and component selection. We further illustrate the methodology on the breast cancer data from The Cancer Genome Atlas repository. K E Y W O R D Sdata integration, dimension reduction, multiblock methods, principal component analysis, structured sparsity

Canonical correlation analysis investigates linear relationships between two sets of variables, but often works poorly on modern data sets due to high-dimensionality and mixed data types (continuous/binary/zero-inflated). We propose a new approach for sparse canonical correlation analysis of mixed data types that does not require explicit parametric assumptions. Our main contribution is the use of truncated latent Gaussian copula to model the data with excess zeroes, which allows us to derive a rank-based estimator of latent correlation matrix without the estimation of marginal transformation functions. The resulting semiparametric sparse canonical correlation analysis method works well in high-dimensional settings as demonstrated via numerical studies, and application to the analysis of association between gene expression and micro RNA data of breast cancer patients.

This article considers the problem of sparse estimation of canonical vectors in linear discriminant analysis when p N . Several methods have been proposed in the literature that estimate one canonical vector in the two-group case. However, G − 1 canonical vectors can be considered if the number of groups is G. In the multi-group context, it is common to estimate canonical vectors in a sequential fashion. Moreover, separate prior estimation of the covariance structure is often required. We propose a novel methodology for direct estimation of canonical vectors. In contrast to existing techniques, the proposed method estimates all canonical vectors at once, performs variable selection across all the vectors and comes with theoretical guarantees on the variable selection and classification consistency. First, we highlight the fact that in the N > p setting the canonical vectors can be expressed in a closed form up to an orthogonal transformation. Secondly, we propose an extension of this form to the p N setting and achieve feature selection by using a group penalty. The resulting optimization problem is convex and can be solved using a block-coordinate descent algorithm. The practical performance of the method is evaluated through simulation studies as well as real data applications.