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Christian L. Mueller

Publications and source records attributed to Christian L. Mueller.

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Sparse regression, classification, and microbial network estimation in QIIME2 with q2-classo and q2-gglasso

Motivation: Statistical analysis of microbial count data derived from 16S rRNA or metagenomics sequencing poses unique challenges due to the sparse, compositional, and high-dimensional nature of the data. While QIIME 2 already provides many tools for data pre-processing and analysis, plugins for statistical regression, classification, and microbial network estimation tailored to compositional count data are relatively scarce. Results: We present q2-classo and q2-gglasso, two novel QIIME 2 plugins that implement penalized regression, classification, and graphical modeling approaches for microbial compositional data. q2-classo enables the prediction of a continuous or binary outcome of interest using compositional microbiome data as predictors. Both sparse log-contrast regression and classification, as well as tree-aggregated log-contrast models are available. q2-gglasso enables the estimation of taxon-taxon association networks through sparse graphical model estimation, such as, e.g., the SPIEC-EASI framework, as well as adaptive and latent graphical models. The latent model can decompose taxon-taxon associations into a sparse direct interaction matrix and a latent (low-rank) matrix which enables robust principal component embedding of a data set. Within the QIIME 2 ecosystem we demonstrate their application on the Atacama soil microbiome dataset, illustrating robust model selection, classification, and microbial network estimation with covariates and latent factors. Availability: The software is freely available under the BSD-3-Clause License. Source code is available at https://github.com/bio-datascience/q2-gglasso and https://github.com/bio-datascience/q2-classo-latest, with installation through QIIME 2 and Docker.

q-bio.QM

Sparse and compositionally robust inference of microbial ecological networks

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. Secondly, microbial sequencing-based studies typically measure hundreds of OTUs on only tens to hundreds of samples; thus, inference of OTU-OTU interaction networks is severely under-powered, and additional assumptions are required for accurate inference. Here, we present SPIEC-EASI (SParse InversE Covariance Estimation for Ecological Association Inference), a statistical method for the inference of microbial ecological interactions from metagenomic datasets that addresses both of these issues. SPIEC-EASI combines data transformations developed for compositional data analysis with a graphical model inference framework that assumes the underlying ecological interaction network is sparse. To reconstruct the interaction network, SPIEC-EASI relies on algorithms for sparse neighborhood and inverse covariance selection. Because no large-scale microbial ecological networks have been experimentally validated, SPIEC-EASI comprises computational tools to generate realistic OTU count data from a set of diverse underlying network topologies. SPIEC-EASI outperforms state-of-the-art methods in terms of edge recovery and network properties on realistic synthetic data under a variety of scenarios. SPIEC-EASI also reproducibly predicts previously unknown microbial interactions using data from the American Gut project.

stat.AP