get.pair: get.pair to predict enhancer-gene linkages.

In ELMER: Inferring Regulatory Element Landscapes and Transcription Factor Networks Using Cancer Methylomes

Description

get.pair is a function to predict enhancer-gene linkages using associations between DNA methylation at enhancer CpG sites and expression of 20 nearby genes of the CpG sites (see reference). Two files will be saved if save is true: getPair.XX.all.pairs.statistic.csv and getPair.XX.pairs.significant.csv (see detail).

Usage

get.pair(data,
         nearGenes,
         minSubgroupFrac = 0.4,
         permu.size = 10000,
         permu.dir = NULL,
         raw.pvalue = 0.001,
         Pe = 0.001,
         mode = "unsupervised",
         diff.dir = NULL,
         dir.out = "./",
         diffExp = FALSE,
         group.col,
         group1 = NULL,
         group2 = NULL,
         cores = 1,
         correlation = "negative",
         filter.probes = TRUE,
         filter.portion = 0.3,
         filter.percentage = 0.05,
         label = NULL,
         addDistNearestTSS = FALSE,
         save = TRUE)

Arguments

data	A multiAssayExperiment with DNA methylation and Gene Expression data. See createMAE function.
nearGenes	Can be either a list containing output of GetNearGenes function or path of rda file containing output of GetNearGenes function.
minSubgroupFrac	A number ranging from 0 to 1, specifying the fraction of extreme samples that define group U (unmethylated) and group M (methylated), which are used to link probes to genes. The default is 0.4 (the lowest quintile of samples is the U group and the highest quintile samples is the M group) because we typically want to be able to detect a specific (possibly unknown) molecular subtype among tumor; these subtypes often make up only a minority of samples, and 20% was chosen as a lower bound for the purposes of statistical power. If you are using pre-defined group labels, such as treated replicates vs. untreated replicated, use a value of 1.0 (Supervised mode).
permu.size	A number specify the times of permuation used in the unsupervised mode. Default is 10000.
permu.dir	A path where the output of permutation will be.
raw.pvalue	A number specify the raw p-value cutoff for defining significant pairs. Default is 0.001. It will select the significant P value cutoff before calculating the empirical p-values.
Pe	A number specify the empirical p-value cutoff for defining significant pairs. Default is 0.001
mode	A character. Can be "unsupervised" or "supervised". If unsupervised is set the U (unmethylated) and M (methylated) groups will be selected among all samples based on methylation of each probe. Otherwise U group and M group will set as the samples of group1 or group2 as described below: If diff.dir is "hypo, U will be the group 1 and M the group2. If diff.dir is "hyper" M group will be the group1 and U the group2.
diff.dir	A character can be "hypo" or "hyper", showing differential methylation direction in group 1. It can be "hypo" which means the probes are hypomethylated in group1; "hyper" which means the probes are hypermethylated in group1; This argument is used only when mode is supervised nad it should be the same value from get.diff.meth function.
dir.out	A path specify the directory for outputs. Default is current directory
diffExp	A logic. Default is FALSE. If TRUE, t test will be applied to test whether putative target gene are differentially expressed between two groups.
group.col	A column defining the groups of the sample. You can view the available columns using: colnames(MultiAssayExperiment::colData(data)).
group1	A group from group.col. ELMER will run group1 vs group2. That means, if direction is hyper, get probes hypermethylated in group 1 compared to group 2.
group2	A group from group.col. ELMER will run group1 vs group2. That means, if direction is hyper, get probes hypermethylated in group 1 compared to group 2.
cores	A interger which defines number of core to be used in parallel process. Default is 1: don't use parallel process.
correlation	Type of correlation to evaluate (negative or positive). Negative (default) checks if hypomethylated region has a upregulated target gene. Positive checks if region hypermethylated has a upregulated target gene.
filter.probes	Should filter probes by selecting only probes that have at least a certain number of samples below and above a certain cut-off. See preAssociationProbeFiltering function.
filter.portion	A number specify the cut point to define binary methylation level for probe loci. Default is 0.3. When beta value is above 0.3, the probe is methylated and vice versa. For one probe, the percentage of methylated and unmethylated samples should be above filter.percentage value. Only used if filter.probes is TRUE. See preAssociationProbeFiltering function.
filter.percentage	Minimun percentage of samples to be considered in methylated and unmethylated for the filter.portion option. Default 5%. Only used if filter.probes is TRUE. See preAssociationProbeFiltering function.
label	A character labels the outputs.
addDistNearestTSS	Calculated distance to the nearest TSS instead of gene distance. Having to calculate the distance to nearest TSS will take some time.
save	Two files will be saved if save is true: getPair.XX.all.pairs.statistic.csv and getPair.XX.pairs.significant.csv (see detail).

Value

Statistics for all pairs and significant pairs

Author(s)

Lijing Yao (creator: [e-mail]) Tiago C Silva (maintainer: [e-mail])

References

Yao, Lijing, et al. "Inferring regulatory element landscapes and transcription factor networks from cancer methylomes." Genome biology 16.1 (2015): 1.

Examples

data <- ELMER:::getdata("elmer.data.example")
nearGenes <-GetNearGenes(TRange=getMet(data)[c("cg00329272","cg10097755"),],
                         geneAnnot=getExp(data))
Hypo.pair <- get.pair(data=data,
                       nearGenes=nearGenes,
                       permu.size=5,
                       group.col = "definition",
                       group1 = "Primary solid Tumor",
                       group2 = "Solid Tissue Normal",
                       raw.pvalue = 0.2,
                       Pe = 0.2,
                       dir.out="./",
                       label= "hypo")

Hypo.pair <- get.pair(data = data,
                      nearGenes = nearGenes,
                      permu.size = 5,
                      raw.pvalue = 0.2,
                      Pe = 0.2,
                      dir.out = "./",
                      diffExp = TRUE,
                      group.col = "definition",
                      group1 = "Primary solid Tumor",
                      group2 = "Solid Tissue Normal",
                      label = "hypo")

ELMER documentation built on Nov. 8, 2020, 4:59 p.m.