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Latent Interacting Variable Effects (LIVE) modeling is a framework to integrate different types of microbiome multi-omics data by combining latent variables from single-omic models into a structured meta-model to determine discriminative, interacting multi-omics features driving disease status. We implemented and tested LIVE modeling in publicly available metagenomics and metabolomics datasets from Crohn’s Disease and Ulcerative Colitis patients. Here, LIVE modeling reduced the number of feature correlations from the original data set for CD and UC to tractable numbers and facilitated prioritization of biological associations between microbes, metabolites, enzymes and IBD status through the application of stringent thresholds on generated inferential statistics. We determined LIVE modeling confirmed previously reported IBD biomarkers and uncovered potentially novel disease mechanisms in IBD. LIVE modeling makes a distinct and complementary contribution to the current methods to integrate microbiome data to predict IBD status because of its flexibility to adapt to different types of microbiome multi-omics data, scalability for large and small cohort studies via reliance on latent variables and dimensionality reduction, and the intuitive interpretability of the linear meta-model integrating -omic data types. The results of LIVE modeling and the biological relationships can be represented in networks that connect local correlation structure of single omic data types with global community and omic structure in the latent variable VIP scores. This model arises as novel tool that allows researchers to be more selective about omic feature interaction without disrupting the structural correlation framework provided by sPLS-DA interaction effects modeling. It will lead to form testable hypothesis by identifying potential and unique interactions between metabolome and microbiome that must be considered for future studies.
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Microbiome Subcommunity Learning with Logistic-Tree Normal Latent Dirichlet Allocation
Abstract Mixed-membership (MM) models such as latent Dirichlet allocation (LDA) have been applied to microbiome compositional data to identify latent subcommunities of microbial species. These subcommunities are informative for understanding the biological interplay of microbes and for predicting health outcomes. However, microbiome compositions typically display substantial cross-sample heterogeneities in subcommunity compositions—that is, the variability in the proportions of microbes in shared subcommunities across samples—which is not accounted for in prior analyses. As a result, LDA can produce inference, which is highly sensitive to the specification of the number of subcommunities and often divides a single subcommunity into multiple artificial ones. To address this limitation, we incorporate the logistic-tree normal (LTN) model into LDA to form a new MM model. This model allows cross-sample variation in the composition of each subcommunity around some “centroid” composition that defines the subcommunity. Incorporation of auxiliary Pólya-Gamma variables enables a computationally efficient collapsed blocked Gibbs sampler to carry out Bayesian inference under this model. By accounting for such heterogeneity, our new model restores the robustness of the inference in the specification of the number of subcommunities and allows meaningful subcommunities to be identified.
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- Award ID(s):
- 1749789
- PAR ID:
- 10486003
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Biometrics
- Volume:
- 79
- Issue:
- 3
- ISSN:
- 0006-341X
- Format(s):
- Medium: X Size: p. 2321-2332
- Size(s):
- p. 2321-2332
- Sponsoring Org:
- National Science Foundation
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