Contents

1 Introduction

BERT (Batch-Effect Removal with Trees) offers flexible and efficient batch effect correction of omics data, while providing maximum tolerance to missing values. Tested on multiple datasets from proteomic analyses, BERT offered a typical 5-10x runtime improvement over existing methods, while retaining more numeric values and preserving batch effect reduction quality.

As such, BERT is a valuable preprocessing tool for data analysis workflows, in particular for proteomic data. By providing BERT via Bioconductor, we make this tool available to a wider research community. An accompanying research paper is currently under preparation and will be made public soon.

BERT addresses the same fundamental data integration challenges than the [HarmonizR][https://github.com/HSU-HPC/HarmonizR] package, which is released on Bioconductor in November 2023. However, various algorithmic modications and optimizations of BERT provide better execution time and better data coverage than HarmonizR. Moreover, BERT offers a more user-friendly design and a less error-prone input format.

Please note that our package BERT is neither affiliated with nor related to Bidirectional Encoder Representations from Transformers as published by Google.

Please report any questions and issues in the GitHub forum, the BioConductor forum or directly contact the authors,

2 Installation

Please download and install a current version of R (Windows binaries). You might want to consider installing a development environment as well, e.g. RStudio. Finally, BERT can be installed via Bioconductor using

if (!require("BiocManager", quietly = TRUE)){
    install.packages("BiocManager")
}
BiocManager::install("BERT")

which will install all required dependencies. To install the development version of BERT, you can use devtools as follows

devtools::install_github("HSU-HPC/BERT")

which may require the manual installation of the dependencies sva and limma.

if (!require("BiocManager", quietly = TRUE)){
    install.packages("BiocManager")
}
BiocManager::install("sva")
BiocManager::install("limma")

3 Data Preparation

As input, BERT requires a dataframe1 Matrices and SummarizedExperiments work as well, but will automatically be converted to dataframes. with samples in rows and features in columns. For each sample, the respective batch should be indicated by an integer or string in a corresponding column labelled Batch. Missing values should be labelled as NA. A valid example dataframe could look like this:

example = data.frame(feature_1 = stats::rnorm(5), feature_2 = stats::rnorm(5), Batch=c(1,1,2,2,2))
example
#>    feature_1  feature_2 Batch
#> 1 -1.6936693  0.5351165     1
#> 2  0.7076116 -0.2652192     1
#> 3  0.6187245 -1.0494814     2
#> 4  0.4270551 -0.6184051     2
#> 5 -1.1487432 -0.3736748     2

Note that each batch should contain at least two samples. Optional columns that can be passed are

Note that BERT tries to find all metadata information for a SummarizedExperiment, including the mandatory batch information, using colData. For instance, a valid SummarizedExperiment might be defined as

nrows <- 200
ncols <- 8
expr_values <- matrix(runif(nrows * ncols, 1, 1e4), nrows)
# colData also takes all other metadata information, such as Label, Sample,
# Covariables etc.
colData <- data.frame(Batch=c(1,1,1,1,2,2,2,2), Reference=c(1,1,0,0,1,1,0,0))
dataset_raw = SummarizedExperiment::SummarizedExperiment(assays=list(expr=expr_values), colData=colData)

4 Basic Usage

BERT can be invoked by importing the BERT library and calling the BERT function. The batch effect corrected data is returned as a dataframe that mirrors the input dataframe2 In particular, the row and column names are in the same order and the optional columns are preserved..

library(BERT)
# generate test data with 10% missing values as provided by the BERT library
dataset_raw <- generate_dataset(features=60, batches=10, samplesperbatch=10, mvstmt=0.1, classes=2)
# apply BERT
dataset_adjusted <- BERT(dataset_raw)
#> 2025-03-25 17:36:32.00226 INFO::Formatting Data.
#> 2025-03-25 17:36:32.01941 INFO::Replacing NaNs with NAs.
#> 2025-03-25 17:36:32.036719 INFO::Removing potential empty rows and columns
#> 2025-03-25 17:36:32.654053 INFO::Found  600  missing values.
#> 2025-03-25 17:36:32.676634 INFO::Introduced 0 missing values due to singular proteins at batch/covariate level.
#> 2025-03-25 17:36:32.678342 INFO::Done
#> 2025-03-25 17:36:32.679867 INFO::Acquiring quality metrics before batch effect correction.
#> 2025-03-25 17:36:32.708546 INFO::Starting hierarchical adjustment
#> 2025-03-25 17:36:32.710762 INFO::Found  10  batches.
#> 2025-03-25 17:36:32.712321 INFO::Cores argument is not defined or BPPARAM has been specified. Argument corereduction will not be used.
#> 2025-03-25 17:36:34.127235 INFO::Using default BPPARAM
#> 2025-03-25 17:36:34.128221 INFO::Processing subtree level 1
#> 2025-03-25 17:36:44.570009 INFO::Processing subtree level 2
#> 2025-03-25 17:36:54.967364 INFO::Adjusting the last 1 batches sequentially
#> 2025-03-25 17:36:54.969839 INFO::Done
#> 2025-03-25 17:36:54.971218 INFO::Acquiring quality metrics after batch effect correction.
#> 2025-03-25 17:36:54.979149 INFO::ASW Batch was 0.48938839333745 prior to batch effect correction and is now -0.115395967880642 .
#> 2025-03-25 17:36:54.980585 INFO::ASW Label was 0.330063084450311 prior to batch effect correction and is now 0.770211653162659 .
#> 2025-03-25 17:36:54.982392 INFO::Total function execution time is  23.0532038211823  s and adjustment time is  22.2597069740295 s ( 96.56 )

BERT uses the logging library to convey live information to the user during the adjustment procedure. The algorithm first verifies the shape and suitability of the input dataframe (lines 1-6) before continuing with the actual batch effect correction (lines 8-14). BERT measure batch effects before and after the correction step by means of the average silhouette score (ASW) with respect to batch and labels (lines 7 and 15). The ASW Label should increase in a successful batch effect correction, whereas low values (\(\leq 0\)) are desireable for the ASW Batch3 The optimum of ASW Label is 1, which is typically however not achieved on real-world datasets. Also, the optimum of ASW Batch can vary, depending on the class distributions of the batches.. Finally, BERT prints the total function execution time (including the computation time for the quality metrics).

5 Advanced Options

5.1 Parameters

BERT offers a large number of parameters to customize the batch effect adjustment. The full function call, including all defaults is

BERT(data, cores = NULL, combatmode = 1, corereduction=2, stopParBatches=2, backend="default", method="ComBat", qualitycontrol=TRUE, verify=TRUE, labelname="Label", batchname="Batch", referencename="Reference", samplename="Sample", covariatename=NULL, BPPARAM=NULL, assayname=NULL)

In the following, we list the respective meaning of each parameter: - data: The input dataframe/matrix/SummarizedExperiment to adjust. See Data Preparation for detailed formatting instructions. - data The data for batch-effect correction. Must contain at least two samples per batch and 2 features.

  • cores: BERT uses BiocParallel for parallelization. If the user specifies a value cores, BERT internally creates and uses a new instance of BiocParallelParam, which is however not exhibited to the user. Setting this parameter can speed up the batch effect adjustment considerably, in particular for large datasets and on unix-based operating systems. A value between \(2\) and \(4\) is a reasonable choice for typical commodity hardware. Multi-node computations are not supported as of now. If, however, cores is not specified, BERT will default to BiocParallel::bpparam(), which may have been set by the user or the system. Additionally, the user can directly specify a specific instance of BiocParallelParam to be used via the BPPARAM argument.
  • combatmode An integer that encodes the parameters to use for ComBat.
Value par.prior mean.only
1 TRUE FALSE
2 TRUE TRUE
3 FALSE FALSE
4 FALSE TRUE

The value of this parameter will be ignored, if method!="ComBat".

  • corereduction Positive integer indicating the factor by which the number of processes should be reduced, once no further adjustment is possible for the current number of batches.4 E.g. consider a BERT call with 8 batches and 8 processes. Further adjustment is not possible with this number of processes, since batches are always processed in pairs. With corereduction=2, the number of processes for the following adjustment steps would be set to \(8/2=4\), which is the maximum number of usable processes for this example. This parameter is used only, if the user specified a custom value for parameter cores.

  • stopParBatches Positive integer indicating the minimum number of batches required at a hierarchy level to proceed with parallelized adjustment. If the number of batches is smaller, adjustment will be performed sequentially to avoid communication overheads.

  • backend: The backend to use for inter-process communication. Possible choices are default and file, where the former refers to the default communication backend of the requested parallelization mode and the latter will create temporary .rds files for data communication. ‘default’ is usually faster for small to medium sized datasets.

  • method: The method to use for the underlying batch effect correction steps. Should be either ComBat, limma for limma::removeBatchEffects or ref for adjustment using specified references (cf. Data Preparation). The underlying batch effect adjustment method for ref is a modified version of the limma method.

  • qualitycontrol: A boolean to (de)activate the ASW computation. Deactivating the ASW computations accelerates the computations.

  • verify: A boolean to (de)activate the initial format check of the input data. Deactivating this verification step accelerates the computations.

  • labelname: A string containing the name of the column to use as class labels. The default is “Label”.

  • batchname: A string containing the name of the column to use as batch labels. The default is “Batch”.

  • referencename: A string containing the name of the column to use as reference labels. The default is “Reference”.

  • covariatename: A vector containing the names of columns with categorical covariables.The default is NULL, in which case all column names are matched agains the pattern “Cov”.

  • BPPARAM: An instance of BiocParallelParam that will be used for parallelization. The default is null, in which case the value of cores determines the behaviour of BERT.

  • assayname: If the user chooses to pass a SummarizedExperiment object, they need to specify the name of the assay that they want to apply BERT to here. BERT then returns the input SummarizedExperiment with an additional assay labeled assayname_BERTcorrected.

5.2 Verbosity

BERT utilizes the logging package for output. The user can easily specify the verbosity of BERT by setting the global logging level in the script. For instance

logging::setLevel("WARN") # set level to warn and upwards
result <- BERT(data,cores = 1) # BERT executes silently

5.3 Choosing the Optimal Number of Cores

BERT exhibits a large number of parameters for parallelisation as to provide users with maximum flexibility. For typical scenarios, however, the default parameters are well suited. For very large experiments (\(>15\) batches), we recommend to increase the number of cores (a reasonable value is \(4\) but larger values may be possible on your hardware). Most users should leave all parameters to their respective default.

6 Examples

In the following, we present simple cookbook examples for BERT usage. Note that ASWs (and runtime) will most likely differ on your machine, since the data generating process involves multiple random choices.

6.1 Sequential Adjustment with limma

Here, BERT uses limma as underlying batch effect correction algorithm (method='limma') and performs all computations on a single process (cores parameter is left on default).

# import BERT
library(BERT)
# generate data with 30 batches, 60 features, 15 samples per batch, 15% missing values and 2 classes
dataset_raw <- generate_dataset(features=60, batches=20, samplesperbatch=15, mvstmt=0.15, classes=2)
# BERT
dataset_adjusted <- BERT(dataset_raw, method="limma")
#> 2025-03-25 17:36:55.138869 INFO::Formatting Data.
#> 2025-03-25 17:36:55.139993 INFO::Replacing NaNs with NAs.
#> 2025-03-25 17:36:55.141365 INFO::Removing potential empty rows and columns
#> 2025-03-25 17:36:55.143541 INFO::Found  2700  missing values.
#> 2025-03-25 17:36:55.162495 INFO::Introduced 0 missing values due to singular proteins at batch/covariate level.
#> 2025-03-25 17:36:55.163503 INFO::Done
#> 2025-03-25 17:36:55.164299 INFO::Acquiring quality metrics before batch effect correction.
#> 2025-03-25 17:36:55.181519 INFO::Starting hierarchical adjustment
#> 2025-03-25 17:36:55.182721 INFO::Found  20  batches.
#> 2025-03-25 17:36:55.183525 INFO::Cores argument is not defined or BPPARAM has been specified. Argument corereduction will not be used.
#> 2025-03-25 17:36:55.186485 INFO::Using default BPPARAM
#> 2025-03-25 17:36:55.18727 INFO::Processing subtree level 1
#> 2025-03-25 17:36:57.956606 INFO::Processing subtree level 2
#> 2025-03-25 17:37:00.798027 INFO::Processing subtree level 3
#> 2025-03-25 17:37:03.65951 INFO::Adjusting the last 1 batches sequentially
#> 2025-03-25 17:37:03.662044 INFO::Done
#> 2025-03-25 17:37:03.663339 INFO::Acquiring quality metrics after batch effect correction.
#> 2025-03-25 17:37:03.685502 INFO::ASW Batch was 0.442184686954674 prior to batch effect correction and is now -0.13617068274587 .
#> 2025-03-25 17:37:03.686804 INFO::ASW Label was 0.333414877949537 prior to batch effect correction and is now 0.849402911800612 .
#> 2025-03-25 17:37:03.687842 INFO::Total function execution time is  8.54907584190369  s and adjustment time is  8.4794909954071 s ( 99.19 )

6.2 Parallel Batch Effect Correction with ComBat

Here, BERT uses ComBat as underlying batch effect correction algorithm (method is left on default) and performs all computations on a 2 processes (cores=2).

# import BERT
library(BERT)
# generate data with 30 batches, 60 features, 15 samples per batch, 15% missing values and 2 classes
dataset_raw <- generate_dataset(features=60, batches=20, samplesperbatch=15, mvstmt=0.15, classes=2)
# BERT
dataset_adjusted <- BERT(dataset_raw, cores=2)
#> 2025-03-25 17:37:03.759183 INFO::Formatting Data.
#> 2025-03-25 17:37:03.760349 INFO::Replacing NaNs with NAs.
#> 2025-03-25 17:37:03.761751 INFO::Removing potential empty rows and columns
#> 2025-03-25 17:37:03.763848 INFO::Found  2700  missing values.
#> 2025-03-25 17:37:03.787155 INFO::Introduced 0 missing values due to singular proteins at batch/covariate level.
#> 2025-03-25 17:37:03.788747 INFO::Done
#> 2025-03-25 17:37:03.790083 INFO::Acquiring quality metrics before batch effect correction.
#> 2025-03-25 17:37:03.810063 INFO::Starting hierarchical adjustment
#> 2025-03-25 17:37:03.811368 INFO::Found  20  batches.
#> 2025-03-25 17:37:04.458138 INFO::Set up parallel execution backend with 2 workers
#> 2025-03-25 17:37:04.459804 INFO::Processing subtree level 1 with 20 batches using 2 cores.
#> 2025-03-25 17:37:14.695958 INFO::Adjusting the last 2 batches sequentially
#> 2025-03-25 17:37:14.697458 INFO::Adjusting sequential tree level 1 with 2 batches
#> 2025-03-25 17:37:16.614683 INFO::Done
#> 2025-03-25 17:37:16.616279 INFO::Acquiring quality metrics after batch effect correction.
#> 2025-03-25 17:37:16.640392 INFO::ASW Batch was 0.484187898710007 prior to batch effect correction and is now -0.1238941411423 .
#> 2025-03-25 17:37:16.642024 INFO::ASW Label was 0.280162725003221 prior to batch effect correction and is now 0.864586207754367 .
#> 2025-03-25 17:37:16.643729 INFO::Total function execution time is  12.8845281600952  s and adjustment time is  12.8028650283813 s ( 99.37 )

6.3 Batch Effect Correction Using SummarizedExperiment

Here, BERT takes the input data using a SummarizedExperiment instead. Batch effect correction is then performed using ComBat as underlying algorithm (method is left on default) and all computations are performed on a single process (cores parameter is left on default).

nrows <- 200
ncols <- 8
# SummarizedExperiments store samples in columns and features in rows (in contrast to BERT).
# BERT will automatically account for this.
expr_values <- matrix(runif(nrows * ncols, 1, 1e4), nrows)
# colData also takes further metadata information, such as Label, Sample,
# Reference or Covariables
colData <- data.frame("Batch"=c(1,1,1,1,2,2,2,2), "Label"=c(1,2,1,2,1,2,1,2), "Sample"=c(1,2,3,4,5,6,7,8))
dataset_raw = SummarizedExperiment::SummarizedExperiment(assays=list(expr=expr_values), colData=colData)
dataset_adjusted = BERT(dataset_raw, assayname = "expr")
#> 2025-03-25 17:37:16.757243 INFO::Formatting Data.
#> 2025-03-25 17:37:16.758321 INFO::Recognized SummarizedExperiment
#> 2025-03-25 17:37:16.759242 INFO::Typecasting input to dataframe.
#> 2025-03-25 17:37:16.799194 INFO::Replacing NaNs with NAs.
#> 2025-03-25 17:37:16.800728 INFO::Removing potential empty rows and columns
#> 2025-03-25 17:37:16.804171 INFO::Found  0  missing values.
#> 2025-03-25 17:37:16.81124 INFO::Introduced 0 missing values due to singular proteins at batch/covariate level.
#> 2025-03-25 17:37:16.812287 INFO::Done
#> 2025-03-25 17:37:16.813157 INFO::Acquiring quality metrics before batch effect correction.
#> 2025-03-25 17:37:16.818531 INFO::Starting hierarchical adjustment
#> 2025-03-25 17:37:16.819752 INFO::Found  2  batches.
#> 2025-03-25 17:37:16.822525 INFO::Cores argument is not defined or BPPARAM has been specified. Argument corereduction will not be used.
#> 2025-03-25 17:37:16.823606 INFO::Using default BPPARAM
#> 2025-03-25 17:37:16.824806 INFO::Adjusting the last 2 batches sequentially
#> 2025-03-25 17:37:16.826314 INFO::Adjusting sequential tree level 1 with 2 batches
#> 2025-03-25 17:37:16.884548 INFO::Done
#> 2025-03-25 17:37:16.886121 INFO::Acquiring quality metrics after batch effect correction.
#> 2025-03-25 17:37:16.894749 INFO::ASW Batch was -0.0111326521306665 prior to batch effect correction and is now -0.0944619753411018 .
#> 2025-03-25 17:37:16.896281 INFO::ASW Label was -0.00692476486913961 prior to batch effect correction and is now 0.00524185973685226 .
#> 2025-03-25 17:37:16.89803 INFO::Total function execution time is  0.140705823898315  s and adjustment time is  0.0648980140686035 s ( 46.12 )

6.4 BERT with Covariables

BERT can utilize categorical covariables that are specified in columns Cov_1, Cov_2, .... These columns are automatically detected and integrated into the batch effect correction process.

# import BERT
library(BERT)
# set seed for reproducibility
set.seed(1)
# generate data with 5 batches, 60 features, 30 samples per batch, 15% missing values and 2 classes
dataset_raw <- generate_dataset(features=60, batches=5, samplesperbatch=30, mvstmt=0.15, classes=2)
# create covariable column with 2 possible values, e.g. male/female condition
dataset_raw["Cov_1"] = sample(c(1,2), size=dim(dataset_raw)[1], replace=TRUE)
# BERT
dataset_adjusted <- BERT(dataset_raw)
#> 2025-03-25 17:37:16.987956 INFO::Formatting Data.
#> 2025-03-25 17:37:16.989173 INFO::Replacing NaNs with NAs.
#> 2025-03-25 17:37:16.990579 INFO::Removing potential empty rows and columns
#> 2025-03-25 17:37:16.992845 INFO::Found  1350  missing values.
#> 2025-03-25 17:37:16.99452 INFO::BERT requires at least 2 numeric values per batch/covariate level. This may reduce the number of adjustable features considerably, depending on the quantification technique.
#> 2025-03-25 17:37:17.014391 INFO::Introduced 0 missing values due to singular proteins at batch/covariate level.
#> 2025-03-25 17:37:17.015469 INFO::Done
#> 2025-03-25 17:37:17.01636 INFO::Acquiring quality metrics before batch effect correction.
#> 2025-03-25 17:37:17.02355 INFO::Starting hierarchical adjustment
#> 2025-03-25 17:37:17.026776 INFO::Found  5  batches.
#> 2025-03-25 17:37:17.028169 INFO::Cores argument is not defined or BPPARAM has been specified. Argument corereduction will not be used.
#> 2025-03-25 17:37:17.029482 INFO::Using default BPPARAM
#> 2025-03-25 17:37:17.030787 INFO::Processing subtree level 1
#> 2025-03-25 17:37:27.311538 INFO::Adjusting the last 2 batches sequentially
#> 2025-03-25 17:37:27.313839 INFO::Adjusting sequential tree level 1 with 2 batches
#> 2025-03-25 17:37:27.380006 INFO::Done
#> 2025-03-25 17:37:27.381526 INFO::Acquiring quality metrics after batch effect correction.
#> 2025-03-25 17:37:27.392241 INFO::ASW Batch was 0.492773245691086 prior to batch effect correction and is now -0.0377157224767566 .
#> 2025-03-25 17:37:27.393865 INFO::ASW Label was 0.40854766060101 prior to batch effect correction and is now 0.895560693013661 .
#> 2025-03-25 17:37:27.39564 INFO::Total function execution time is  10.4076769351959  s and adjustment time is  10.3535668849945 s ( 99.48 )

6.5 BERT with references

In rare cases, class distributions across experiments may be severely skewed. In particular, a batch might contain classes that other batches don’t contain. In these cases, samples of common conditions may serve as references (bridges) between the batches (method="ref"). BERT utilizes those samples as references that have a condition specified in the “Reference” column of the input. All other samples are co-adjusted. Please note, that this strategy implicitly uses limma as underlying batch effect correction algorithm.

# import BERT
library(BERT)
# generate data with 4 batches, 6 features, 15 samples per batch, 15% missing values and 2 classes
dataset_raw <- generate_dataset(features=6, batches=4, samplesperbatch=15, mvstmt=0.15, classes=2)
# create reference column with default value 0.  The 0 indicates, that the respective sample should be co-adjusted only.
dataset_raw[, "Reference"] <- 0
# randomly select 2 references per batch and class - in practice, this choice will be determined by external requirements (e.g. class known for only these samples)
batches <- unique(dataset_raw$Batch) # all the batches
for(b in batches){ # iterate over all batches
    # references from class 1
    ref_idx = sample(which((dataset_raw$Batch==b)&(dataset_raw$Label==1)), size=2, replace=FALSE)
    dataset_raw[ref_idx, "Reference"] <- 1
    # references from class 2
    ref_idx = sample(which((dataset_raw$Batch==b)&(dataset_raw$Label==2)), size=2, replace=FALSE)
    dataset_raw[ref_idx, "Reference"] <- 2
}
# BERT
dataset_adjusted <- BERT(dataset_raw, method="ref")
#> 2025-03-25 17:37:27.509169 INFO::Formatting Data.
#> 2025-03-25 17:37:27.510358 INFO::Replacing NaNs with NAs.
#> 2025-03-25 17:37:27.511624 INFO::Removing potential empty rows and columns
#> 2025-03-25 17:37:27.512873 INFO::Found  60  missing values.
#> 2025-03-25 17:37:27.516309 INFO::Introduced 0 missing values due to singular proteins at batch/covariate level.
#> 2025-03-25 17:37:27.517116 INFO::Done
#> 2025-03-25 17:37:27.517901 INFO::Acquiring quality metrics before batch effect correction.
#> 2025-03-25 17:37:27.521085 INFO::Starting hierarchical adjustment
#> 2025-03-25 17:37:27.52206 INFO::Found  4  batches.
#> 2025-03-25 17:37:27.522825 INFO::Cores argument is not defined or BPPARAM has been specified. Argument corereduction will not be used.
#> 2025-03-25 17:37:27.525587 INFO::Using default BPPARAM
#> 2025-03-25 17:37:27.526388 INFO::Processing subtree level 1
#> 2025-03-25 17:37:30.414121 INFO::Adjusting the last 2 batches sequentially
#> 2025-03-25 17:37:30.416299 INFO::Adjusting sequential tree level 1 with 2 batches
#> 2025-03-25 17:37:30.439175 INFO::Done
#> 2025-03-25 17:37:30.440551 INFO::Acquiring quality metrics after batch effect correction.
#> 2025-03-25 17:37:30.445441 INFO::ASW Batch was 0.440355021914032 prior to batch effect correction and is now -0.087480278736629 .
#> 2025-03-25 17:37:30.446745 INFO::ASW Label was 0.373906827748893 prior to batch effect correction and is now 0.919791677398366 .
#> 2025-03-25 17:37:30.448233 INFO::Total function execution time is  2.9390881061554  s and adjustment time is  2.91718697547913 s ( 99.25 )

7 Issues

Issues can be reported in the GitHub forum, the BioConductor forum or directly to the authors.

8 License

This code is published under the GPLv3.0 License and is available for non-commercial academic purposes.

9 Reference

Please cite our manuscript, if you use BERT for your research: Schumann Y, Gocke A, Neumann J (2024). Computational Methods for Data Integration and Imputation of Missing Values in Omics Datasets. PROTEOMICS. ISSN 1615-9861, doi:10.1002/pmic.202400100

10 Session Info

sessionInfo()
#> R Under development (unstable) (2025-03-01 r87860 ucrt)
#> Platform: x86_64-w64-mingw32/x64
#> Running under: Windows Server 2022 x64 (build 20348)
#> 
#> Matrix products: default
#>   LAPACK version 3.12.0
#> 
#> locale:
#> [1] LC_COLLATE=C                          
#> [2] LC_CTYPE=English_United States.utf8   
#> [3] LC_MONETARY=English_United States.utf8
#> [4] LC_NUMERIC=C                          
#> [5] LC_TIME=English_United States.utf8    
#> 
#> time zone: America/New_York
#> tzcode source: internal
#> 
#> attached base packages:
#> [1] stats     graphics  grDevices utils     datasets  methods   base     
#> 
#> other attached packages:
#> [1] BERT_1.3.6       BiocStyle_2.35.0
#> 
#> loaded via a namespace (and not attached):
#>  [1] tidyselect_1.2.1            blob_1.2.4                 
#>  [3] Biostrings_2.75.4           fastmap_1.2.0              
#>  [5] janitor_2.2.1               XML_3.99-0.18              
#>  [7] digest_0.6.37               timechange_0.3.0           
#>  [9] lifecycle_1.0.4             cluster_2.1.8.1            
#> [11] statmod_1.5.0               survival_3.8-3             
#> [13] KEGGREST_1.47.0             invgamma_1.1               
#> [15] RSQLite_2.3.9               magrittr_2.0.3             
#> [17] genefilter_1.89.0           compiler_4.5.0             
#> [19] rlang_1.1.5                 sass_0.4.9                 
#> [21] tools_4.5.0                 yaml_2.3.10                
#> [23] knitr_1.50                  S4Arrays_1.7.3             
#> [25] bit_4.6.0                   DelayedArray_0.33.6        
#> [27] abind_1.4-8                 BiocParallel_1.41.2        
#> [29] BiocGenerics_0.53.6         grid_4.5.0                 
#> [31] stats4_4.5.0                xtable_1.8-4               
#> [33] edgeR_4.5.9                 iterators_1.0.14           
#> [35] logging_0.10-108            SummarizedExperiment_1.37.0
#> [37] cli_3.6.4                   rmarkdown_2.29             
#> [39] crayon_1.5.3                generics_0.1.3             
#> [41] httr_1.4.7                  DBI_1.2.3                  
#> [43] cachem_1.1.0                stringr_1.5.1              
#> [45] splines_4.5.0               parallel_4.5.0             
#> [47] AnnotationDbi_1.69.0        BiocManager_1.30.25        
#> [49] XVector_0.47.2              matrixStats_1.5.0          
#> [51] vctrs_0.6.5                 Matrix_1.7-3               
#> [53] jsonlite_1.9.1              sva_3.55.0                 
#> [55] bookdown_0.42               comprehenr_0.6.10          
#> [57] IRanges_2.41.3              S4Vectors_0.45.4           
#> [59] bit64_4.6.0-1               locfit_1.5-9.12            
#> [61] foreach_1.5.2               limma_3.63.10              
#> [63] jquerylib_0.1.4             snow_0.4-4                 
#> [65] annotate_1.85.0             glue_1.8.0                 
#> [67] codetools_0.2-20            lubridate_1.9.4            
#> [69] stringi_1.8.4               GenomeInfoDb_1.43.4        
#> [71] GenomicRanges_1.59.1        UCSC.utils_1.3.1           
#> [73] htmltools_0.5.8.1           GenomeInfoDbData_1.2.14    
#> [75] R6_2.6.1                    evaluate_1.0.3             
#> [77] lattice_0.22-6              Biobase_2.67.0             
#> [79] png_0.1-8                   memoise_2.0.1              
#> [81] snakecase_0.11.1            bslib_0.9.0                
#> [83] SparseArray_1.7.7           nlme_3.1-167               
#> [85] mgcv_1.9-1                  xfun_0.51                  
#> [87] MatrixGenerics_1.19.1