DRAGGER provides a toolkit for drug repositioning based on variant and gene-expression data. It includes a wrapper for a basic workflow, but a custom run can be set up with ease.
You can install the development version of DRAGGER from GitHub with:
# install.packages("devtools")
devtools::install_github("AEstebanMar/DRAGGER")DRAGGER includes a demo dataset to showcase its main use case.
library(DRAGGER)
head(GWAS_demo)
#> variant_id pvalue beta_number
#> 1 rs2710888 2e-57 0.0115
#> 2 rs3934834 2e-29 0.0097
#> 3 rs182532 1e-18 -0.0163
#> 4 rs17160669 1e-28 0.0100
#> 5 rs9660106 2e-12 0.0044
#> 6 rs425277 2e-166 0.0191
head(GTEx)
#> Tissue gene_id gene_name strand
#> 1 Adipose_Subcutaneous ENSG00000227232.5 WASH7P -
#> 2 Adipose_Subcutaneous ENSG00000268903.1 RP11-34P13.15 -
#> 3 Adipose_Subcutaneous ENSG00000269981.1 RP11-34P13.16 -
#> 4 Adipose_Subcutaneous ENSG00000241860.6 RP11-34P13.13 -
#> 5 Adipose_Subcutaneous ENSG00000279457.4 RP11-34P13.18 -
#> 6 Adipose_Subcutaneous ENSG00000228463.9 AP006222.2 -
#> variant_information tss_distance rs_id_dbSNP151_GRCh38p7 pval_nominal
#> 1 chr1_64764_C_T_b38 35211 rs769952832 1.01661e-08
#> 2 chr1_103147_C_T_b38 -32748 rs866355763 3.47332e-04
#> 3 chr1_108826_G_C_b38 -29139 rs62642117 1.19525e-04
#> 4 chr1_14677_G_A_b38 -159185 rs201327123 7.91948e-08
#> 5 chr1_599167_G_A_b38 403756 rs188376087 1.53694e-07
#> 6 chr1_280550_G_A_b38 -16952 rs1206875823 2.72051e-20
#> slope
#> 1 0.586346
#> 2 -0.612097
#> 3 0.431229
#> 4 0.700658
#> 5 -0.687794
#> 6 -1.822030
head(DGIdb)
#> gene_name entrez_id interaction_claim_source interaction_types
#> 1 CDK7 1022 CancerCommons inhibitor
#> 2 VDR 7421 DTC Missing
#> 3 GPR55 9290 DTC Missing
#> 4 NR1H4 9971 DTC Missing
#> 5 FGFR2 2263 JAX-CKB Missing
#> 6 APOE 348 NCI Missing
#> drug_claim_name drug_concept_id interaction_group_score PMIDs
#> 1 SNS-032 chembl:CHEMBL296468 0.82 Missing
#> 2 NIFEKALANT chembl:CHEMBL360861 0.14 Missing
#> 3 BISACODYL chembl:CHEMBL942 0.94 Missing
#> 4 PENTACHLOROPHENOL chembl:CHEMBL75967 0.07 Missing
#> 5 AZ6089 Missing NA 22869148
#> 6 PREDNISONE chembl:CHEMBL635 0.23 3185288DRAGGER includes a wrapper function, aptly named DRAGGER, which executes the basic workflow. Workflow is described in detail in vignettes, along with customisation options.
library(DRAGGER)
demo <- DRAGGER(GWAS_demo, GTEx, DGIdb)
#>
#>
#> Parsing variant data
#> Parsing data frame as GWAS data
#> Matching p_val_variant column...
#> Match found. Parsing...
#> Matching beta_value column...
#> No matches found
#> Matching rs_id column...
#> Match found. Parsing...
#> Matching gene_symbol column...
#> No matches found
#> Matching drug_name column...
#> No matches found
#> Sorting input by statistical significance
#>
#>
#> Parsing expression data
#> Parsing data frame as GTEx data
#> Matching p_val_nominal column...
#> Match found. Parsing...
#> Matching rs_id column...
#> Match found. Parsing...
#> Matching gene_symbol column...
#> Match found. Parsing...
#> Matching drug_name column...
#> No matches found
#>
#>
#> Parsing drug-gene data
#> Parsing data frame as DGIdb data
#> Matching rs_id column...
#> No matches found
#> Matching gene_symbol column...
#> Match found. Parsing...
#> Matching drug_name column...
#> Match found. Parsing...
#> Merging genes and variants
#> Merging with drug database
#> Predicting beneficial drug effect
#> Producing list of candidates for repositioning
head(demo)
#> gene_symbol rs_id p_val_variant beta_number Tissue
#> 1 AAK1 rs3899666 2e-28 0.0076 Esophagus_Muscularis
#> 2 AAK1 rs3899666 2e-28 0.0076 Esophagus_Muscularis
#> 3 AAK1 rs3899666 2e-28 0.0076 Esophagus_Muscularis
#> 4 AAK1 rs12987661 9e-12 -0.0078 Kidney_Cortex
#> 5 AAK1 rs12987661 9e-12 -0.0078 Kidney_Cortex
#> 6 AAK1 rs12987661 9e-12 -0.0078 Kidney_Cortex
#> gene_id strand variant_information tss_distance p_val_nominal
#> 1 ENSG00000115977.18 - chr2_69640739_C_T_b38 -33610 1.00569e-07
#> 2 ENSG00000115977.18 - chr2_69640739_C_T_b38 -33610 1.00569e-07
#> 3 ENSG00000115977.18 - chr2_69640739_C_T_b38 -33610 1.00569e-07
#> 4 ENSG00000115977.18 - chr2_69586326_T_C_b38 -88023 1.00882e-04
#> 5 ENSG00000115977.18 - chr2_69586326_T_C_b38 -88023 1.00882e-04
#> 6 ENSG00000115977.18 - chr2_69586326_T_C_b38 -88023 1.00882e-04
#> slope entrez_id interaction_claim_source interaction_types drug_name
#> 1 -0.195734 22848 GuideToPharmacology inhibitor 223366123
#> 2 -0.195734 22848 TTD Missing LX9211
#> 3 -0.195734 22848 GuideToPharmacology inhibitor 384403682
#> 4 -0.495702 22848 GuideToPharmacology inhibitor 223366123
#> 5 -0.495702 22848 TTD Missing LX9211
#> 6 -0.495702 22848 GuideToPharmacology inhibitor 384403682
#> drug_concept_id interaction_group_score PMIDs prediction candidate
#> 1 chembl:CHEMBL2105759 7.96 Missing activator FALSE
#> 2 Missing NA Missing activator FALSE
#> 3 Missing NA Missing activator FALSE
#> 4 chembl:CHEMBL2105759 7.96 Missing inhibitor TRUE
#> 5 Missing NA Missing inhibitor FALSE
#> 6 Missing NA Missing inhibitor TRUEHere is a preview of the type of plots included in DRAGGER, also heavily customisable.
library(DRAGGER)
demo <- suppressMessages(DRAGGER(GWAS_demo, GTEx, DGIdb))
plot_volcano(demo)
barplot_by_groups(demo, "rs_id", "candidate")
library(DRAGGER)
demo <- suppressMessages(DRAGGER(GWAS_demo, GTEx, DGIdb))
test_chi2(demo, "Tissue", "brain", "stomach",
"candidate", TRUE, FALSE)
#> Warning in chisq.test(chisq_table): Chi-squared approximation may be incorrect
#> $table
#> candidate_TRUE candidate_FALSE
#> Tissue_brain 309 0
#> Tissue_stomach 1548 17
#>
#> $chi2
#> X2 p.value Cramer_V
#> 1 2.286645 0.1304917 0.03493129