xEnricherSNPs: Function to conduct enrichment analysis given a list of SNPs...

Description Usage Arguments Value Note See Also Examples

View source: R/xEnricherSNPs.r

Description

xEnricherSNPs is supposed to conduct enrichment analysis given the input data and the ontology in query. It returns an object of class "eTerm". Enrichment analysis is based on either Fisher's exact test or Hypergeometric test. The test can respect the hierarchy of the ontology. Now it supports enrichment analysis for SNPs using GWAS Catalog traits mapped to Experimental Factor Ontology. If required, additional SNPs that are in linkage disequilibrium (LD) with input SNPs are also be used for test.

Usage

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xEnricherSNPs(data, background = NULL, ontology = c("EF", "EF_disease",
"EF_phenotype", "EF_bp"), include.LD = NA, LD.r2 = 0.8,
size.range = c(10, 2000), min.overlap = 3, which.distance = NULL,
test = c("hypergeo", "fisher", "binomial"), p.adjust.method = c("BH",
"BY", "bonferroni", "holm", "hochberg", "hommel"),
ontology.algorithm = c("none", "pc", "elim", "lea"), elim.pvalue =
0.01,
lea.depth = 2, path.mode = c("all_paths", "shortest_paths",
"all_shortest_paths"), true.path.rule = T, verbose = T,
RData.location = "http://galahad.well.ox.ac.uk/bigdata")

Arguments

data

an input vector. It contains a list of SNPs of interest

background

a background vector. It contains a list of SNPs as the test background. If NULL, by default all annotatable are used as background

ontology

the ontology supported currently. Now it is only "EF" for Experimental Factor Ontology (used to annotate GWAS Catalog SNPs). However, there are several subparts of this ontology to choose: 'EF_disease' for the subpart under the term 'disease' (EFO:0000408), 'EF_phenotype' for the subpart under the term 'phenotype' (EFO:0000651), 'EF_bp' for the subpart under the term 'biological process' (GO:0008150)

include.LD

additional SNPs in LD with Lead SNPs are also included. By default, it is 'NA' to disable this option. Otherwise, LD SNPs will be included based on one or more of 26 populations and 5 super populations from 1000 Genomics Project data (phase 3). The population can be one of 5 super populations ("AFR", "AMR", "EAS", "EUR", "SAS"), or one of 26 populations ("ACB", "ASW", "BEB", "CDX", "CEU", "CHB", "CHS", "CLM", "ESN", "FIN", "GBR", "GIH", "GWD", "IBS", "ITU", "JPT", "KHV", "LWK", "MSL", "MXL", "PEL", "PJL", "PUR", "STU", "TSI", "YRI"). Explanations for population code can be found at http://www.1000genomes.org/faq/which-populations-are-part-your-study

LD.r2

the LD r2 value. By default, it is 0.8, meaning that SNPs in LD (r2>=0.8) with input SNPs will be considered as LD SNPs. It can be any value from 0.8 to 1

size.range

the minimum and maximum size of members of each term in consideration. By default, it sets to a minimum of 10 but no more than 2000

min.overlap

the minimum number of overlaps. Only those terms with members that overlap with input data at least min.overlap (3 by default) will be processed

which.distance

which terms with the distance away from the ontology root (if any) is used to restrict terms in consideration. By default, it sets to 'NULL' to consider all distances

test

the test statistic used. It can be "fisher" for using fisher's exact test, "hypergeo" for using hypergeometric test, or "binomial" for using binomial test. Fisher's exact test is to test the independence between gene group (genes belonging to a group or not) and gene annotation (genes annotated by a term or not), and thus compare sampling to the left part of background (after sampling without replacement). Hypergeometric test is to sample at random (without replacement) from the background containing annotated and non-annotated genes, and thus compare sampling to background. Unlike hypergeometric test, binomial test is to sample at random (with replacement) from the background with the constant probability. In terms of the ease of finding the significance, they are in order: hypergeometric test > fisher's exact test > binomial test. In other words, in terms of the calculated p-value, hypergeometric test < fisher's exact test < binomial test

p.adjust.method

the method used to adjust p-values. It can be one of "BH", "BY", "bonferroni", "holm", "hochberg" and "hommel". The first two methods "BH" (widely used) and "BY" control the false discovery rate (FDR: the expected proportion of false discoveries amongst the rejected hypotheses); the last four methods "bonferroni", "holm", "hochberg" and "hommel" are designed to give strong control of the family-wise error rate (FWER). Notes: FDR is a less stringent condition than FWER

ontology.algorithm

the algorithm used to account for the hierarchy of the ontology. It can be one of "none", "pc", "elim" and "lea". For details, please see 'Note' below

elim.pvalue

the parameter only used when "ontology.algorithm" is "elim". It is used to control how to declare a signficantly enriched term (and subsequently all genes in this term are eliminated from all its ancestors)

lea.depth

the parameter only used when "ontology.algorithm" is "lea". It is used to control how many maximum depth is used to consider the children of a term (and subsequently all genes in these children term are eliminated from the use for the recalculation of the signifance at this term)

path.mode

the mode of paths induced by vertices/nodes with input annotation data. It can be "all_paths" for all possible paths to the root, "shortest_paths" for only one path to the root (for each node in query), "all_shortest_paths" for all shortest paths to the root (i.e. for each node, find all shortest paths with the equal lengths)

true.path.rule

logical to indicate whether the true-path rule should be applied to propagate annotations. By default, it sets to true

verbose

logical to indicate whether the messages will be displayed in the screen. By default, it sets to false for no display

RData.location

the characters to tell the location of built-in RData files. See xRDataLoader for details

Value

an object of class "eTerm", a list with following components:

Note

The interpretation of the algorithms used to account for the hierarchy of the ontology is:

See Also

xRDataLoader, xEnricher

Examples

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## Not run: 
# Load the library
library(XGR)

# SNP-based enrichment analysis using GWAS Catalog traits (mapped to EF)
# a) provide the input SNPs of interest (eg 'EFO:0002690' for 'systemic lupus erythematosus')
## load GWAS SNPs annotated by EF (an object of class "dgCMatrix" storing a spare matrix)
anno <- xRDataLoader(RData='GWAS2EF')
ind <- which(colnames(anno)=='EFO:0002690')
data <- rownames(anno)[anno[,ind]==1]
data

# optionally, provide the test background (if not provided, all annotatable SNPs)
#background <- rownames(anno)

# b) perform enrichment analysis
eTerm <- xEnricherSNPs(data=data, ontology="EF",
path.mode=c("all_paths"))

# b') optionally, enrichment analysis for input SNPs plus their LD SNPs
## LD based on European population (EUR) with r2>=0.8
#eTerm <- xEnricherSNPs(data=data, include.LD="EUR", LD.r2=0.8)

# c) view enrichment results for the top significant terms
xEnrichViewer(eTerm)

# d) save enrichment results to the file called 'EF_enrichments.txt'
res <- xEnrichViewer(eTerm, top_num=length(eTerm$adjp), sortBy="adjp",
details=TRUE)
output <- data.frame(term=rownames(res), res)
utils::write.table(output, file="EF_enrichments.txt", sep="\t",
row.names=FALSE)

# e) barplot of significant enrichment results
bp <- xEnrichBarplot(eTerm, top_num="auto", displayBy="adjp")
print(bp)

# f) visualise the top 10 significant terms in the ontology hierarchy
# color-code terms according to the adjust p-values (taking the form of 10-based negative logarithm)
xEnrichDAGplot(eTerm, top_num=10, displayBy="adjp",
node.info=c("full_term_name"))
# color-code terms according to the z-scores
xEnrichDAGplot(eTerm, top_num=10, displayBy="zscore",
node.info=c("full_term_name"))

## End(Not run)

XGR documentation built on May 31, 2017, 1:49 a.m.

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