ABAEnrichment (version 1.2.2)

ABAEnrichment-package: Gene expression enrichment in human brain regions

Description

The package ABAEnrichment is designed to test for enrichment of user defined candidate genes in the set of expressed genes in different human brain regions. The package integrates the expression of the candidate gene set (averaged across donors) and the structural information of the brain using an ontology, both provided by the Allen Brain Atlas project [1-4]. The statistical analysis is performed by the core function aba_enrich which interfaces the ontology enrichment software FUNC [5]. Additional functions provided in this package like get_expression and plot_expression facilitate exploring the expression data.

Details

Package:

ABAEnrichment

Type:

Package

Version:

0.99.6

Date:

2015-08-26

License:

GPL (>= 2)

For details see vignette("ABAEnrichment",package="ABAEnrichment")

References

[1] Hawrylycz, M.J. et al. (2012) An anatomically comprehensive atlas of the adult human brain transcriptome, Nature 489: 391-399. doi:10.1038/nature11405 [2] Miller, J.A. et al. (2014) Transcriptional landscape of the prenatal human brain, Nature 508: 199-206. doi:10.1038/nature13185 [3] Allen Institute for Brain Science. Allen Human Brain Atlas [Internet]. Available from: http://human.brain-map.org/ [4] Allen Institute for Brain Science. BrainSpan Atlas of the Developing Human Brain [Internet]. Available from: http://brainspan.org/ [5] Pruefer, K. et al. (2007) FUNC: A package for detecting significant associations between gene sets and ontological, BMC Bioinformatics 8: 41. doi:10.1186/1471-2105-8-41

See Also

vignette("ABAEnrichment",package="ABAEnrichment") vignette("ABAData",package="ABAData") aba_enrich get_expression plot_expression get_name get_sampled_substructures get_superstructures

Examples

#### Perform gene expression enrichment analysis on 13 test genes in five developmental 
#### stages of the human brain using the hypergeometric test implemented in FUNC[5]   
## create input vector with test genes 
genes=rep(1,13)
names(genes)=c('NCAPG', 'APOL4', 'NGFR', 'NXPH4', 'C21orf59', 'CACNG2', 'AGTR1', 'ANO1', 
  'BTBD3', 'MTUS1', 'CALB1', 'GYG1', 'PAX2')
## run enrichment analysis 
res=aba_enrich(genes,dataset='5_stages',cutoff_quantiles=c(0.5,0.7,0.9),n_randsets=100)

## get expression data for the first 10 brain structures of the enrichment analysis output 
get_expression(res$results$structure_id[1:10],background=FALSE)
## plot this expression with dendrogram
plot_expression(res$results$structure_id[1:10],dendro=TRUE,age_category=1)
## plot expression from the 10 highest scoring brain structures 
## in age category 3 without dendrogram
plot_expression(res$results[res$results$age_category==3,'structure_id'][1:10],
  dendro=FALSE,age_category=3)
## get the full name of a structure given the structure id
get_name('Allen:10657')
## get ids of the substructers of 'Allen:10208' that have expression data annotated
get_sampled_substructures('Allen:10208')
## get ids of the superstructers of 'Allen:10208' 
get_superstructures('Allen:10208')

#### Perform gene expression enrichment analysis on 15 test genes in the adult human brain 
#### using the wilcoxon rank test implemented in FUNC[5] 
## create input vector with random scores associated with the test genes (using entrez-Ids)
genes=sample(1:50,15)
names(genes)=c(324,8312,673,1029,64764,1499,3021,3417,3418,8085,3845,9968,5290,5727,5728)
## run enrichment analysis
res=aba_enrich(genes,dataset='adult',test='wilcoxon',cutoff_quantiles=c(0.2,0.5,0.8),
  n_randsets=100)

## plot expression from the 10 highest scoring brain structures without dendrogram
plot_expression(res$results$structure_id[1:10],dendro=FALSE)


#### Explore expression data idependently from enrichment analysis
## get expression data for six genes in the brain structure 'Allen:4010' 
get_expression(structure_ids=c('Allen:4010'),gene_ids=c(324,8312,673,1029,64764,1499),
  dataset='adult')
## plot this expression
plot_expression(structure_ids=c('Allen:4010'),gene_ids=c(324,8312,673,1029,64764,1499),
  dataset='adult')
## 'Allen:4010' apparently was not sampled directly
## get the names of the substructures that provide expression data for 'Allen:4010'
get_name(get_sampled_substructures('Allen:4010'))
## plot expression data of six genes in two brain regions 
## from children (3-11 yrs, age_category 3)
plot_expression(structure_ids=c('Allen:10657','Allen:10208'), 
  gene_ids=c('ENSG00000168036', 'ENSG00000157764', 'ENSG00000182158', 'ENSG00000147889', 
  'ENSG00000103126', 'ENSG00000134982'),dataset='5_stages',dendro=FALSE, age_category=3)
## get developmental effect scores of six genes in two brain regions
get_expression(structure_ids=c('Allen:10657','Allen:10208'), gene_ids=c('ENSG00000168036', 
  'ENSG00000157764', 'ENSG00000182158', 'ENSG00000147889'),dataset='dev_effect')