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Type Package Package BDMMAcorrect March 6, 2019 Title Meta-analysis for the metagenomic read counts data from different cohorts Version 1.0.1 Author ZHENWEI DAI <daizwhao@gmail.com> Maintainer ZHENWEI DAI <daizwhao@gmail.com> Date 2018-10-27 Metagenomic sequencing techniques enable quantitative analyses of the microbiome. However, combining the microbial data from these experiments is challenging due to the variations between experiments. The existing methods for correcting batch effects do not consider the interactions between variables microbial taxa in microbial studies and the overdispersion of the microbiome data. Therefore, they are not applicable to microbiome data. We develop a new method, Bayesian Dirichlet-multinomial regression metaanalysis (BDMMA), to simultaneously model the batch effects and detect the microbial taxa associated with phenotypes. BDMMA automatically models the dependence among microbial taxa and is robust to the high dimensionality of the microbiome and their association sparsity. License GPL (>= 2) Depends R (>= 3.5), vegan, ellipse, ggplot2, ape, SummarizedExperiment Encoding UTF-8 LazyData true Imports Rcpp (>= 0.12.12), RcppArmadillo, RcppEigen, stats LinkingTo Rcpp, RcppArmadillo, RcppEigen biocviews ImmunoOncology, BatchEffect, Microbiome, Bayesian RoxygenNote 6.0.1 Suggests knitr, rmarkdown, BiocGenerics VignetteBuilder knitr git_url https://git.bioconductor.org/packages/bdmmacorrect git_branch RELEASE_3_8 git_last_commit 6fe7f5f git_last_commit_date 2019-01-04 Date/Publication 2019-03-06 1

2 BDMMA R topics documented: BDMMA.......................................... 2 fdr_cut............................................ 3 L_mean........................................... 4 Microbiome_dat....................................... 4 trace_plot.......................................... 5 VBatch........................................... 5 Index 7 BDMMA Bayesian Dirichlet Multinomial approach for meta-analysis of metagenomic read counts Bayesian Dirichlet Multinomial approach for meta-analysis of metagenomic read counts BDMMA(Microbiome_dat, abundance_threshold = 5e-05, burn_in = 5000, sample_period = 5000, bfdr = 0.1, PIPcut = 0.5) Microbiome_dat A SummarizedExperiment object that includes the taxonomy read counts, phenotypes and batch labels. abundance_threshold The minimum abundance level for the taxa to be included (default value = 5e- 05). burn_in The length of burn in period before sampling the parameters (default value = 5,000). sample_period The length of sampling period for estimating parameters distribution (default value = 5,000) bfdr The false discovery rate level to control (default value = 0.1). PIPcut The threshold to cut the posterior inclusion probabilities (PIPs). By default, PIP is thresholding at 0.5. A list contains the selected taxa and summary of parameters included in the model. selected.taxa A list includes the selected taxa fesatures that are significantly associated with the main effect variable. parameter_summary A data.frame contains the mean and quantiles of the parameters included in the model. Each row includes a parameter s distribution summary and the parameter name is labeled in the first row. alpha_g: the baseline intercept of g-th taxon; betaj_g: the association strength between the g-th taxon and j-th input variables; deltai_g: the batch effect parameter of batch i, taxon g; L_g: the posterior selection probability of g-th taxon; p: the proportion of significantly associated taxa; eta: the standard deviation of the spike distribution (in the spike-and-slab prior).

fdr_cut 3 PIP bfdr A vector contains the PIPs of selected microbial taxa. The corresponding bfdr under the selected microbial taxa. References Dai, Zhenwei, et al. "Batch Effects Correction for Microbiome Data with Dirichlet-multinomial Regression." Bioinformatics 1 (2018): 8. require(summarizedexperiment) data(microbiome_dat) ## (not run) ## output <- BDMMA(Microbiome_dat, burn_in = 3000, sample_period = 3000) fdr_cut Threshold the posterior inclusion probability (PIP) through control Bayesian false discovery rate (bfdr). Threshold the posterior inclusion probability (PIP) through control Bayesian false discovery rate (bfdr). fdr_cut(pip_vec, alpha = 0.1) PIP_vec A vector contains the PIPs of parameters alpha The level of the bfdr to need to control (default = 0.1) The cutoff for PIPs to control the bfdr with the user defined value, alpha. data(l_mean) cutoff <- fdr_cut(l_mean, alpha = 0.1)

4 Microbiome_dat L_mean Posterior Inclusion Probabilities (PIP) A dataset containing the posterior inclusion probabilities of 40 variables L_mean Format A numeric vector including 40 PIP values Microbiome_dat Taxonomy Reads and Associated Phenotypes Simualated taxonomy read counts of 40 taxa and their associated phenotypes. Microbiome_dat Format SummarizedExperiment Details The dataset contains the simualated taxonomy read counts from 80 samples, where the samples come from 4 different batches and include both case and control samples in each batch. For the detailed usuage, please see the package vignette.

trace_plot 5 trace_plot Trace plot of BDMMA output Trace plot of BDMMA output trace_plot(trace, param, col = "black") trace param col A data.frame named "trace" contained in the output of function BDMMA A character vector including the parameters name for trace_plot A string defining the color of trace plot (default color is black) The function returns a list containing plot objects of parameters trace plot. require(summarizedexperiment) data(microbiome_dat) ## (not run) ## output <- BDMMA(Microbiome_dat, burn_in = 3000, sample_period = 3000) ## figure <- trace_plot(output$trace, param = c("alpha_1", "beta1_10")) ## print(figure) VBatch Visualize batch effect with principal coordinate analysis Visualize batch effect with principal coordinate analysis VBatch(Microbiome_dat, main_variable = NULL, method = "bray") Microbiome_dat A SummarizedExperiment object that includes the taxonomy read counts, phenotypes and batch labels. main_variable method Optional. A vector containing the main effect variable. Only for categorical main effect variable.the function will generate a figure for each catagory. A string indicating which method should be used to calculate the distance matrix for principal coordinate analysis.

6 VBatch The function returns a list containing plot objects of principal coordinate analysis figures. data(microbiome_dat) figure <- VBatch(Microbiome_dat, method = "bray") print(figure)

Index Topic datasets L_mean, 4 Microbiome_dat, 4 BDMMA, 2 fdr_cut, 3 L_mean, 4 Microbiome_dat, 4 trace_plot, 5 VBatch, 5 7