Microbial communities analysis is drawing growing attention due to the rapid development of high-throughput sequencing techniques nowadays. The observed data has the following typical characteristics: it is high-dimensional, compositional (lying in a simplex) and even would be leptokurtic and highly skewed due to the existence of overly abundant taxa, which makes the conventional correlation analysis infeasible to study the co-occurrence and co-exclusion relationship between microbial taxa. In this article, we address the challenges of covariance estimation for this kind of data. Assuming the basis covariance matrix lying in a well-recognized class of sparse covariance matrices, we adopt a proxy matrix known as centered log-ratio covariance matrix in the literature, which is approximately indistinguishable from the real basis covariance matrix as the dimensionality tends to infinity. We construct a Median-of-Means (MOM) estimator for the centered log-ratio covariance matrix and propose a thresholding procedure that is adaptive to the variability of individual entries. By imposing a much weaker finite fourth moment condition compared with the sub-Gaussianity condition in the literature, we derive the optimal rate of convergence under the spectral norm. In addition, we also provide theoretical guarantee on support recovery. The adaptive thresholding procedure of the MOM estimator is easy to implement and gains robustness when outliers or heavy-tailedness exist. Thorough simulation studies are conducted to show the advantages of the proposed procedure over some state-of-the-arts methods. At last, we apply the proposed method to analyze a microbiome dataset in human gut. The R script for implementing the method is available at https://github.com/heyongstat/RCEC.
Understanding how microbes interact with each other is key to revealing the underlying role that microorganisms play in the host or environment and to identifying microorganisms as an agent that can potentially alter the host or environment. For example, understanding how the microbial interactions associate with parasitic infection can help resolve potential drug or diagnostic test for parasitic infection. To unravel the microbial interactions, existing tools often rely on graphical models to infer the conditional dependence of microbial abundances to represent their interactions. However, cu…
16S-ribosomal sequencing and other metagonomic techniques provide snapshots of microbial communities, revealing phylogeny and the abundances of microbial populations across diverse ecosystems. While changes in microbial community structure are demonstrably associated with certain environmental conditions, identification of underlying mechanisms requires new statistical tools, as these datasets present several technical challenges. First, the abundances of microbial operational taxonomic units (OTUs) from 16S datasets are compositional, and thus, microbial abundances are not independent. Second…
The interactions between microbial taxa in microbiome data has been under great research interest in the science community. In particular, several methods such as SPIEC-EASI, gCoda, and CD-trace have been proposed to model the conditional dependency between microbial taxa, in order to eliminate the detection of spurious correlations. However, all those methods are built upon the central log-ratio (CLR) transformation, which results in a degenerate covariance matrix and thus an undefined inverse covariance matrix as the estimation of the underlying network. Jiang et al. (2021) and Tian et al. (…
High throughput sequencing (HTS) continues to expand our understanding of microbial communities, despite insufficient sequencing depths to detect all rare taxa. These low abundance taxa are not accounted for in existing methods for detecting changes in species richness. We address this with a new hierarchical model that permits rigorous testing for both heterogeneity and biodiversity changes, and simultaneously improves Type I & II error rates compared to existing methods.
Microorganisms play a critical role in host health. The advancement of high-throughput sequencing technology provides opportunities for a deeper understanding of microbial interactions. However, due to the limitations of 16S ribosomal RNA sequencing, microbiome data are zero-inflated, and a quantitative comparison of microbial abundances cannot be made across subjects. By leveraging a recent microbiome profiling technique that quantifies 16S ribosomal RNA microbial counts, we propose a novel Bayesian graphical model that incorporates microorganisms' evolutionary history through a phylogenetic …
In microbiome and genomic studies, the regression of compositional data has been a crucial tool for identifying microbial taxa or genes that are associated with clinical phenotypes. To account for the variation in sequencing depth, the classic log-contrast model is often used where read counts are normalized into compositions. However, zero read counts and the randomness in covariates remain critical issues. In this article, we introduce a surprisingly simple, interpretable, and efficient method for the estimation of compositional data regression through the lens of a novel high-dimensional lo…
Human microbiome studies use sequencing technologies to measure the abundance of bacterial species or Operational Taxonomic Units (OTUs) in samples of biological material. Typically the data are organized in contingency tables with OTU counts across heterogeneous biological samples. In the microbial ecology community, ordination methods are frequently used to investigate latent factors or clusters that capture and describe variations of OTU counts across biological samples. It remains important to evaluate how uncertainty in estimates of each biological sample's microbial distribution propagat…
One of the major research questions regarding human microbiome studies is the feasibility of designing interventions that modulate the composition of the microbiome to promote health and cure disease. This requires extensive understanding of the modulating factors of the microbiome, such as dietary intake, as well as the relation between microbial composition and phenotypic outcomes, such as body mass index (BMI). Previous efforts have modeled these data separately, employing two-step approaches that can produce biased interpretations of the results. Here, we propose a Bayesian joint model tha…
Testing Microbiome Community Differences in High Dimensions: A Bootstrap Approach for Compositional Data
Indian Institute of Technology Bombay（印度理工学院孟买分校）；Missouri University of Science and Technology（密苏里科技大学）；Washington University in St. Louis（圣路易斯华盛顿大学）；University of Missouri（密苏里大学）；University of Michigan（密歇根大学）
Many biological high-throughput data sets, such as targeted amplicon-based and metagenomic sequencing data, are compositional in nature. A common exploratory data analysis task is to infer statistical associations between the high-dimensional microbial compositions and habitat- or host-related covariates. We propose a general robust statistical regression framework, RobRegCC (Robust Regression with Compositional Covariates), which extends the linear log-contrast model by a mean shift formulation for capturing outliers. RobRegCC includes sparsity-promoting convex and non-convex penalties for pa…
High-throughput sequencing technology provides unprecedented opportunities to quantitatively explore human gut microbiome and its relation to diseases. Microbiome data are compositional, sparse, noisy, and heterogeneous, which pose serious challenges for statistical modeling. We propose an identifiable Bayesian multinomial matrix factorization model to infer overlapping clusters on both microbes and hosts. The proposed method represents the observed over-dispersed zero-inflated count matrix as Dirichlet-multinomial mixtures on which latent cluster structures are built hierarchically. Under the…
Microbiome data require statistical models that can simultaneously decode microbes' reaction to the environment and interactions among microbes. While a multiresponse linear regression model seems like a straight-forward solution, we argue that treating it as a graphical model is flawed given that the regression coefficient matrix does not encode the conditional dependence structure between response and predictor nodes as it does not represent the adjacency matrix. This observation is especially important in biological settings when we have prior knowledge on the edges from specific experiment…
An active area of research interest is the inference of ecological models of complex microbial communities. Inferring such ecological models entails understanding the interactions between microbes and how they affect each other's growth. This dissertation employs a statistical perspective to contribute further to the knowledge currently addressing this problem. Part I explains how high-throughput droplet-based microfluidics technology can be used to screen for microbial interactions. An explicit, statistical framework is motivated and developed that can guide the analysis of data from such exp…
