Last data update: 2014.03.03

R: Differential Expression and Enrichment Analysis with...
GeoDE-packageR Documentation

Differential Expression and Enrichment Analysis with (Geo)metrical(D)ifferential(E)expression.

Description

This package contains functions for performing multivariate analysis of geneome-wide expression data and also enrichment analysis.

Details

Package: GeoDE
Type: Package
Version: 1.0
Date: 2014-06-06
License: GPL-2

Given gene expression data from two classes (e.g. controll verses perturbed samples) with biological replicates in each class, this package can be used to extract the most significant genes and gene-sets.

Differential expression is characterised with a single direction in expression space, which can be interpreted to extract the most signiicant genes: this is achieved with the chdirAnalysis function.

Once the characeristic direction has been calculated gene-set enrichmnet can be evaluated using the PAEAAnalysis function. The user is free to use any library of gene-sets, however, included in this package is a broad range of gene-set libraries listed below:

BioCarta_pathways.gmt

Cancer_Cell_Line_Encyclopedia.gmt

ChEA.gmt

Chromosome_location.gmt

CORUM.gmt.gmt

GeneOntology_BP.gmt

GeneOntology_CC.gmt

GeneOntology_MF.gmt

GeneSigDB.gmt

Genome_Browser_PWMs.gmt

HMDB_Metabolites.gmt

Human_Gene_Atlas.gmt

KEA.gmt

KEGG_pathways.gmt

MGI_MP_top3.gmt

MGI_MP_top4.gmt

microRNA.gmt

Mouse_Gene_Atlas.gmt

NCI60.gmt

NURSA-IPMS.gmt

OMIM_disease_genes.gmt

OMIM_Expanded.gmt

Pfam-InterPro-domains.gmt

PPI_Hub_Proteins.gmt

Reactome_pathways.gmt

TF_PPIs.gmt

VirusMINT.gmt

WikiPathways_pathways.gmt

Author(s)

Author: Neil Clark and Avi Ma'ayan

Maintainer: Neil R. Clark <neil.clark@mssm.edu>

References

Clark, Neil R., et al. "The characteristic direction: a geometrical approach to identify differentially expressed genes." BMC bioinformatics 15.1 (2014): 79.

Examples


##################################
#
# An example characteristic direction analysis
#
##################################

# Load the example data

data(example_expression_data)
data(example_sampleclass)
data(example_gammas)

# Examine the expression data
head(example_expression_data)

# Examine the corresponding sample class factor
example_sampleclass

# Run the analysis
chdir_analysis_example <- chdirAnalysis(example_expression_data,example_sampleclass,example_gammas
,CalculateSig=TRUE,nnull=10)

# Examine the results with the first value of the shrinkage parameter (gamma)

# show the first few of the most important genes.

lapply(chdir_analysis_example$results, function(x) x[1:10])

# We can also extract the results of the code{chdirSig} function
# for example chdir_analysis_example$chdirprops[[1]] gives the whole
# characteristic direction vector for each value of gamma:

lapply(chdir_analysis_example$chdirprops[[1]],head)

# and the estimated number of significant genes can be recovered with

chdir_analysis_example$chdirprops$number_sig_genes

##################################
#
# An example PAEA analysis
#
##################################
# Load the expression data

data(example_expression_data)
data(example_sampleclass)
data(example_gammas)

#load a gmt file
data(GeneOntology_BP.gmt)

# Run the characteristic direction analysis
chdir_analysis_example <- chdirAnalysis(example_expression_data,example_sampleclass,example_gammas
,CalculateSig=FALSE)

# Run the PAEA analysis

PAEAtest <- PAEAAnalysis(chdir_analysis_example$chdirprops, gmt[1:100], example_gammas)

# Examine the p values

PAEAtest$p_values

# Examine the principal angles

PAEAtest$principal_angles

##################################
#
# An example multigmtPAEA analysis
#
##################################
# Load the expression data

data(example_expression_data)
data(example_sampleclass)
data(example_gammas)

#load GMT file names
data(AllGMTfiles)

# Run the characteristic direction analysis
chdir_analysis_example <- chdirAnalysis(example_expression_data,example_sampleclass,example_gammas
,CalculateSig=FALSE)

# Run the PAEA analysis over the first two GMT files in the library

multiPAEAtest <- multigmtPAEAAnalysis(chdir_analysis_example$chdirprops, AllGMTfiles[2:3],
example_gammas)

# To run on all the gmt files

#multiPAEAtestAll <- multigmtPAEAAnalysis(chdir_analysis_example$chdirprops, gammas=example_gammas)



Results


R version 3.3.1 (2016-06-21) -- "Bug in Your Hair"
Copyright (C) 2016 The R Foundation for Statistical Computing
Platform: x86_64-pc-linux-gnu (64-bit)

R is free software and comes with ABSOLUTELY NO WARRANTY.
You are welcome to redistribute it under certain conditions.
Type 'license()' or 'licence()' for distribution details.

R is a collaborative project with many contributors.
Type 'contributors()' for more information and
'citation()' on how to cite R or R packages in publications.

Type 'demo()' for some demos, 'help()' for on-line help, or
'help.start()' for an HTML browser interface to help.
Type 'q()' to quit R.

> library(GeoDE)
Loading required package: Matrix
Loading required package: MASS
> png(filename="/home/ddbj/snapshot/RGM3/R_CC/result/GeoDE/GeoDE-package.Rd_%03d_medium.png", width=480, height=480)
> ### Name: GeoDE-package
> ### Title: Differential Expression and Enrichment Analysis with
> ###   (Geo)metrical(D)ifferential(E)expression.
> ### Aliases: GeoDE-package GeoDE
> ### Keywords: package gene differential expression enrichmnet multivariate
> ###   characteristic direction
> 
> ### ** Examples
> 
> 
> ##################################
> #
> # An example characteristic direction analysis
> #
> ##################################
> 
> # Load the example data
> 
> data(example_expression_data)
> data(example_sampleclass)
> data(example_gammas)
> 
> # Examine the expression data
> head(example_expression_data)
  genenames  Controll Controll.1 Controll.2      Pert.    Pert..1   Pert..2
1   MTERFD2 138.64200 167.130000 156.199000 186.640000 122.005000 161.38200
2     SCRIB  52.65380  38.977800  68.963200  94.300900  60.634300  99.01180
3      ZXDC  59.37390  53.952500  55.103300  82.780500  52.770000  80.15000
4    MRPL32 333.80200 375.288000 475.200000 477.085000 327.193000 468.31600
5     WDR69   0.33557   0.614205   0.989874   0.421603   0.890432   1.05624
6     FOXL1   1.03177   0.901720   1.644250   1.170400   1.337110   1.31237
> 
> # Examine the corresponding sample class factor
> example_sampleclass
[1] 1 1 1 2 2 2
Levels: 1 2
> 
> # Run the analysis
> chdir_analysis_example <- chdirAnalysis(example_expression_data,example_sampleclass,example_gammas
+ ,CalculateSig=TRUE,nnull=10)
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> 
> # Examine the results with the first value of the shrinkage parameter (gamma)
> 
> # show the first few of the most important genes.
> 
> lapply(chdir_analysis_example$results, function(x) x[1:10])
[[1]]
      MCL1      LIMD2      RPL27    MRPS18A      TBL1X       SOD1       DPP4 
-0.6078472  0.3791251 -0.3477567  0.2718869 -0.2083958  0.1979625  0.1789876 
      NOX4     POLR2I    ZDHHC20 
 0.1386403 -0.1214708 -0.1193214 

> 
> # We can also extract the results of the code{chdirSig} function
> # for example chdir_analysis_example$chdirprops[[1]] gives the whole
> # characteristic direction vector for each value of gamma:
> 
> lapply(chdir_analysis_example$chdirprops[[1]],head)
[[1]]
                    1
MTERFD2 -0.0005105981
SCRIB    0.0148638842
ZXDC     0.0198058553
MRPL32  -0.0986935062
WDR69   -0.0002376169
FOXL1   -0.0006025896

> 
> # and the estimated number of significant genes can be recovered with
> 
> chdir_analysis_example$chdirprops$number_sig_genes
[[1]]
[1] 88

> 
> ##################################
> #
> # An example PAEA analysis
> #
> ##################################
> # Load the expression data
> 
> data(example_expression_data)
> data(example_sampleclass)
> data(example_gammas)
> 
> #load a gmt file
> data(GeneOntology_BP.gmt)
> 
> # Run the characteristic direction analysis
> chdir_analysis_example <- chdirAnalysis(example_expression_data,example_sampleclass,example_gammas
+ ,CalculateSig=FALSE)
> 
> # Run the PAEA analysis
> 
> PAEAtest <- PAEAAnalysis(chdir_analysis_example$chdirprops, gmt[1:100], example_gammas)
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> 
> # Examine the p values
> 
> PAEAtest$p_values
     translation (GO:0006412)
[1,]               0.01499437
     RNA splicing, via transesterification reactions (GO:0000375)
[1,]                                                    0.5233092
     regulation of secretion (GO:0051046)
[1,]                            0.6557127
     positive regulation of secretion (GO:0051047)
[1,]                                     0.6557127
     cellular amine metabolic process (GO:0009308)
[1,]                                     0.8229856
     signal transduction (GO:0007165) cell communication (GO:0007154)
[1,]                        0.9359704                       0.9657269
     protein complex assembly (GO:0006461) protein secretion (GO:0009306)
[1,]                             0.9900633                              1
     rRNA transcription (GO:0009303)
[1,]                               1
     positive regulation of DNA replication (GO:0045740)
[1,]                                                   1
     respiratory burst (GO:0045730)
[1,]                              1
     positive regulation of protein catabolic process (GO:0045732)
[1,]                                                             1
     positive regulation of DNA repair (GO:0045739)
[1,]                                              1
     negative regulation of adenylate cyclase activity (GO:0007194)
[1,]                                                              1
     inhibition of adenylate cyclase activity by G-protein signaling (GO:0007193)
[1,]                                                                            1
     regulation of transcription factor activity (GO:0051090)
[1,]                                                        1
     activation of adenylate cyclase activity (GO:0007190)
[1,]                                                     1
     positive regulation of transcription factor activity (GO:0051091)
[1,]                                                                 1
     positive regulation of NF-kappaB transcription factor activity (GO:0051092)
[1,]                                                                           1
     response to radiation (GO:0009314)
[1,]                                  1
     oligosaccharide metabolic process (GO:0009311)
[1,]                                              1
     positive regulation of glycogen biosynthetic process (GO:0045725)
[1,]                                                                 1
     positive regulation of tyrosine phosphorylation of Stat3 protein (GO:0042517)
[1,]                                                                             1
     positive regulation of binding (GO:0051099)
[1,]                                           1
     positive regulation of translation (GO:0045727)
[1,]                                               1
     respiratory electron transport chain (GO:0022904)
[1,]                                                 1
     amine biosynthetic process (GO:0009309)
[1,]                                       1
     response to hydrogen peroxide (GO:0042542)
[1,]                                          1
     translational initiation (GO:0006413)
[1,]                                     1
     translational elongation (GO:0006414) RNA export from nucleus (GO:0006405)
[1,]                                     1                                    1
     mRNA export from nucleus (GO:0006406)
[1,]                                     1
     positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531)
[1,]                                                                            1
     negative regulation of cell cycle (GO:0045786)
[1,]                                              1
     ER-associated protein catabolic process (GO:0030433)
[1,]                                                    1
     mRNA catabolic process (GO:0006402)
[1,]                                   1
     positive regulation of cell cycle (GO:0045787)
[1,]                                              1
     tRNA modification (GO:0006400)
[1,]                              1
     positive regulation of cell adhesion (GO:0045785)
[1,]                                                 1
     RNA catabolic process (GO:0006401)
[1,]                                  1
     response to reactive oxygen species (GO:0000302)
[1,]                                                1
     negative regulation of secretion (GO:0051048)
[1,]                                             1
     positive regulation of ossification (GO:0045778)
[1,]                                                1
     negative regulation of transport (GO:0051051)
[1,]                                             1
     superoxide anion generation (GO:0042554)
[1,]                                        1
     regulation of angiogenesis (GO:0045765)
[1,]                                       1
     positive regulation of adenylate cyclase activity (GO:0045762)
[1,]                                                              1
     positive regulation of anti-apoptosis (GO:0045768)
[1,]                                                  1
     positive regulation of angiogenesis (GO:0045766)
[1,]                                                1
     regulation of anti-apoptosis (GO:0045767)
[1,]                                         1
     regulation of S phase (GO:0033261)
[1,]                                  1
     negative regulation of hormone secretion (GO:0046888)
[1,]                                                     1
     positive regulation of lipid biosynthetic process (GO:0046889)
[1,]                                                              1
     protein folding (GO:0006457)
[1,]                            1
     positive regulation of hormone secretion (GO:0046887)
[1,]                                                     1
     reciprocal meiotic recombination (GO:0007131)
[1,]                                             1
     regulation of translational initiation (GO:0006446)
[1,]                                                   1
     regulation of translation (GO:0006417)
[1,]                                      1
     tRNA aminoacylation for protein translation (GO:0006418)
[1,]                                                        1
     meiosis (GO:0007126) phospholipid catabolic process (GO:0009395)
[1,]                    1                                           1
     protein amino acid O-linked glycosylation (GO:0006493)
[1,]                                                      1
     epidermal growth factor receptor signaling pathway (GO:0007173)
[1,]                                                               1
     regulation of epidermal growth factor receptor activity (GO:0007176)
[1,]                                                                    1
     protein amino acid lipidation (GO:0006497)
[1,]                                          1
     transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0007178)
[1,]                                                                                     1
     transforming growth factor beta receptor signaling pathway (GO:0007179)
[1,]                                                                       1
     ATP metabolic process (GO:0046034)
[1,]                                  1
     spliceosomal snRNP biogenesis (GO:0000387)
[1,]                                          1
     endothelial cell migration (GO:0043542)
[1,]                                       1
     G-protein signaling, coupled to cyclic nucleotide second messenger (GO:0007187)
[1,]                                                                               1
     protein amino acid glycosylation (GO:0006486)
[1,]                                             1
     G-protein signaling, coupled to cAMP nucleotide second messenger (GO:0007188)
[1,]                                                                             1
     protein amino acid N-linked glycosylation (GO:0006487)
[1,]                                                      1
     protein amino acid ADP-ribosylation (GO:0006471)
[1,]                                                1
     protein amino acid deph