Dataset Information

MULTI-WAY BLOCKMODELS FOR ANALYZING COORDINATED HIGH-DIMENSIONAL RESPONSES.

ABSTRACT: We consider the problem of quantifying temporal coordination between multiple high-dimensional responses. We introduce a family of multi-way stochastic blockmodels suited for this problem, which avoids pre-processing steps such as binning and thresholding commonly adopted for this type of problems, in biology. We develop two inference procedures based on collapsed Gibbs sampling and variational methods. We provide a thorough evaluation of the proposed methods on simulated data, in terms of membership and blockmodel estimation, predictions out-of-sample, and run-time. We also quantify the effects of censoring procedures such as binning and thresholding on the estimation tasks. We use these models to carry out an empirical analysis of the functional mechanisms driving the coordination between gene expression and metabolite concentrations during carbon and nitrogen starvation, in S. cerevisiae.

SUBMITTER: Airoldi EM

PROVIDER: S-EPMC3935422 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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MULTI-WAY BLOCKMODELS FOR ANALYZING COORDINATED HIGH-DIMENSIONAL RESPONSES.

Airoldi Edoardo M EM Wang Xiaopei X Lin Xiaodong X

The annals of applied statistics 20131201 4

We consider the problem of quantifying temporal coordination between multiple high-dimensional responses. We introduce a family of multi-way stochastic blockmodels suited for this problem, which avoids pre-processing steps such as binning and thresholding commonly adopted for this type of problems, in biology. We develop two inference procedures based on collapsed Gibbs sampling and variational methods. We provide a thorough evaluation of the proposed methods on simulated data, in terms of membe ...[more]

PMID: 24587846

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Project description:Subacute ruminal acidosis (SARA) is a major metabolic disease in lactating dairy cows caused by the excessive intake of high-concentrate diets. Here, we investigated the synergistic responses of rumen bacteria and epithelium to high-grain (HG)-induced SARA. Eight ruminally cannulated lactating Holstein cows were randomly assigned to 2 groups for a 3-week experiment and fed either a conventional (CON) diet or an HG diet. The results showed that the HG-feeding cows had a thickened rumen epithelial papilla with edge injury and a decreased plasma β-hydroxybutyrate concentration. The 16S rRNA gene sequencing results demonstrated that HG feeding caused changes in rumen bacterial structure and composition, which further altered rumen fermentation and metabolism. Cooccurrence network analysis revealed that the distribution of the diet-sensitive bacteria responded to the treatment (CON or HG) and that all diet-sensitive amplicon sequence variants showed low to medium degrees of cooccurrence. Metabolomics analysis indicated that the endothelial permeability-increasing factor prostaglandin E1 and the polyamine synthesis by-product 5'-methylthioadenosine were enriched under HG feeding. Transcriptome analysis suggested that cholesterol biosynthesis genes were upregulated in the rumen epithelium of HG cows. The gene expression changes, coupled with more substrate being available (total volatile fatty acids), may have caused an enrichment of intracellular cholesterol and its metabolites. All of these variations could coordinately stimulate cell proliferation, increase membrane permeability, and trigger epithelial inflammation, which eventually disrupts rumen homeostasis and negatively affects cow health. IMPORTANCE Dairy cows are economically important livestock animals that supply milk for humans. The cow's rumen is a complex and symbiotic ecosystem composed of diverse microorganisms, which has evolved to digest high-fiber diets. In modern dairy production, SARA is a common health problem due to overfeeding of high-concentrate diets for an ever-increasing milk yield. Although extensive studies have been conducted on SARA, it remains unclear how HG feeding affects rumen cross talk homeostasis. Here, we identified structural and taxonomic fluctuation for the rumen bacterial community, an enrichment of certain detrimental metabolites in rumen fluid, and a general upregulation of cholesterol biosynthesis genes in the rumen epithelium of HG-feeding cows by multi-omics analysis. Based on these results, we propose a speculation to explain cellular events of coordinated rumen bacterial and epithelial adaptation to HG diets. Our work provides new insights into the exploitation of molecular regulation strategies to treat and prevent SARA.

Dataset Information

MULTI-WAY BLOCKMODELS FOR ANALYZING COORDINATED HIGH-DIMENSIONAL RESPONSES.

Publications

MULTI-WAY BLOCKMODELS FOR ANALYZING COORDINATED HIGH-DIMENSIONAL RESPONSES.

Similar Datasets

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