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Table 1 Overview and guidance on common and selected R packages used in DNA methylation pipelines as a starting point for making decisions based on the desired estimate. See Heiss et al. [4] for information on the differences between Illumina microarrays and bisulfite sequencing. See table 3 for information on M-values and Beta-values

From: Estimands in epigenome-wide association studies

R function (Package)

Estimates come from

Used input

Full pipeline (DMCs and DMRs)

BioMethyl\(^1\)

 

M-values, Beta-values (BS-seq\(^{\dagger }\))

minfi\(^{2}\)

 

M-values, Beta-values

ChAMP\(^{3}\)

 

M-values, Beta-values

RnBeads\(^{4}\)

 

M-values (BS-seq\(^{\dagger }\))

metilene\(^{5}\)

 

Beta-values (BS-seq\(^{\dagger }\))

Preprocessing\(^{\ddagger }\)

ComBat (sva\(^6\))

 

M-values (BS-seq\(^{\dagger }\))

melon (wateRmelon\(^{7}\))

 

Beta-values

BMIQ (wateRmelon\(^{7}\))

 

Beta-values

SWAN (missMethyl\(^{8}\))

 

Beta-values

CellDMC (EpiDISH\(^9\))

lm (stats)

Beta-values

Detect differentially methylated single CpG sites (DMCs)

champ.DMP (ChAMP\(^3\))

lmFit (limma\(^{10}\))

M-values, Beta-values

dmpFinder (minfi\(^2\))

lmFit (limma\(^{10}\))

M-values, Beta-values

calDEG (BioMethyl\(^1\))

t-test

M-values, Beta-values

varFit (missMethyl\(^{8}\))

lmFit (limma\(^{10}\))

M-values

DMLtest (DSS\(^{11}\))

 

Count values (BS-seq\(^{\dagger }\))

Detect differentially methylated regions (DMRs)

bumphunter (bumphunter\(^{12}\))

lmFit (limma\(^{10}\))

M-values(BS-seq\(^{\dagger }\), after transformation)

champ.DMR (ChAMP\(^3\))

bumphunter (bumphunter\(^{12}\))

M-values

dmrcate (DMRcate\(^{13}\))

lmFit (limma\(^5\))

M-values (BS-seq\(^{\dagger }\))

gometh (missMethyl\(^{8}\))

 

M-values, Beta-values

BSmooth (bsseq\(^{14}\))

 

Beta-values (BS-seq\(^{\dagger }\))

  1. \(^1\)Wang [59], \(^2\)Aryee [32], \(^3\)Tian [31], \(^{4}\)Müller [29], \(^{5}\)Jühling [36],
  2. \(^6\)Johnson [52], \(^{7}\)Pidsley [44], \(^{8}\)Phipson [60], \(^9\)Zheng [35], \(^{10}\)Smyth [34],
  3. \(^{11}\)Park [16] \(^{12}\)Irizarry [61], \(^{13}\)Peters [62], \(^{14}\)Hansen [63]
  4. \(^{\dagger }\)BS-seq: Supports (processed) bisulfite sequencing data. Packages might need “transformed count data”
  5. \(^{\ddagger }\)See Assenov [30] for bisulfite sequencing and McEwen [33] for Illumina microarray data