source("echolocatoR/R/MAIN.R")

PAINTOR

GWAS only

PAINTOR_results <- PAINTOR(GWAS_dataset_name="Nalls23andMe_2019",
                           eQTL_dataset_name=NA,
                           gene="LRRK2",
                           n_causal=5,
                           XGR_dataset=NA, 
                           ROADMAP_search=c("monocyte","brain"),
                           chromatin_state="TssA",
                           no_annotations=T) #******

## [1] "++ PAINTOR:: Only GWAS input data detected. Feeding into PAINTOR..."
## [1] "++ PAINTOR:: Results will be stored in  ==>  ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR"
## [1] "****** Double checking PT_results_path ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR"
## [1] "++ Creating Locus File..."
## [1] "++ PAINTOR:: Creating LD Matrix File..."
## [1] "++ PAINTOR:: Writing LD file to ==>  ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR/LRRK2.Nalls23andMe_2019.NA.ld1"
## [1] "++ PAINTOR:: Creating Annotation Matrix File..."
## [1] "+++ PAINTOR:: no_annotations=T; Prior Probability set to 1 for all SNPs."
## [1] "+ PAINTOR:: Preparing input.files"
## [1] "+ PAINTOR:: Running PAINTOR..."
## [1] "./echolocatoR/tools/PAINTOR_V3.0/PAINTOR -input ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR/input.files -Zhead ZSCORE.P1 -LDname ld1 -mcmc -in ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR -out ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR -Gname Enrichment.Estimates.txt -RESname results.txt -ANname annotations.txt -set_seed 2019"

createDT(PAINTOR_results)

GWAS + Epigenetic Annotations

PAINTOR_results.roadmap <- PAINTOR(GWAS_dataset_name="Nalls23andMe_2019",
                                   eQTL_dataset_name=NA,
                                   gene="LRRK2",
                                   n_causal=5,
                                   XGR_dataset=NA, 
                                   ROADMAP_search=c("monocyte","brain"),
                                   chromatin_state="TssA",
                                   no_annotations=F)

## [1] "++ PAINTOR:: Only GWAS input data detected. Feeding into PAINTOR..."
## [1] "++ PAINTOR:: Results will be stored in  ==>  ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR"
## [1] "****** Double checking PT_results_path ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR"
## [1] "++ Creating Locus File..."
## [1] "++ PAINTOR:: Creating LD Matrix File..."
## [1] "++ PAINTOR:: Writing LD file to ==>  ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR/LRRK2.Nalls23andMe_2019.NA.ld1"
## [1] "++ PAINTOR:: Creating Annotation Matrix File..."

## Warning in if (!is.na(ROADMAP_search)) {: the condition has length > 1 and
## only the first element will be used

## [1] "+++ PAINTOR:: Gathering annotations via ROADMAP server for: monocyte, brain"

## Warning in if (ROADMAP_search == "all_cell_types") {: the condition has
## length > 1 and only the first element will be used

## [1] "++ GoShifter: Searching for Roadmap annotation BED files..."
## [1] "++ GoShifter: Found 15 annotation BED files matching search query."
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E053_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E054_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E067_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E068_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E069_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E070_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E071_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E072_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E073_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E074_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E081_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E082_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E124_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E125_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E029_TssA_subset.bed.gz"
## [1] "++ PAINTOR:: Merging and formatting BED files using PAINTOR utility."
## [1] "+++ PAINTOR:: Decompressing BED files."
## [1] "+++ PAINTOR:: Writing annotations paths file to  ==>  ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR/annotation_paths.txt"
## [1] "+++ PAINTOR:: Annotation--SNP overlap summaries:"
## [1] "+++ PAINTOR:: Removing temporary decompressed BED files."
## [1] "+ PAINTOR:: Preparing input.files"
## [1] "+ PAINTOR:: Running PAINTOR..."
## [1] "./echolocatoR/tools/PAINTOR_V3.0/PAINTOR -input ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR/input.files -Zhead ZSCORE.P1 -LDname ld1 -mcmc -in ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR -out ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR -Gname Enrichment.Estimates.txt -RESname results.txt -ANname annotations.txt -set_seed 2019"

createDT(PAINTOR_results.roadmap)

GWAS + Fairfax eQTLs + Epigenetic Annotations

PAINTOR_results.FF <- PAINTOR(GWAS_dataset_name="Nalls23andMe_2019",
                               eQTL_dataset_name="Fairfax_2014",
                               gene="LRRK2",
                               n_causal=5,
                               XGR_dataset=NA,
                               ROADMAP_search =c("monocyte","brain"),
                               chromatin_state="TssA",
                               no_annotations=F)

## [1] "++ PAINTOR:: GWAS and eQTL input data detected. Feeding both into PAINTOR..."
## [1] "++ PAINTOR:: Results will be stored in  ==>  ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR"
## [1] "****** Double checking PT_results_path ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR"
## [1] "++ Creating Locus File..."
## [1] ""
## [1] "+ Processsing Expression data"
## [1] "++ Extracting probe info"
## [1] "++ CD14"
## [1] "++ IFN"
## [1] "++ LPS2"
## [1] "++ LPS24"
## [1] ""
## [1] "+ Processing Summary Stats data"
## [1] ""
## [1] "+ Processing Genotype data"
## [1] ""
## [1] "+ Merging Summary Stats, Genotype, and Expression data"
## [1] "++ PAINTOR:: Creating LD Matrix File..."
## [1] "++ PAINTOR:: Writing LD file to ==>  ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR/LRRK2.Nalls23andMe_2019.Fairfax_2014.ld1"
## [1] "++ PAINTOR:: Creating Annotation Matrix File..."

## Warning in if (!is.na(ROADMAP_search)) {: the condition has length > 1 and
## only the first element will be used

## [1] "+++ PAINTOR:: Gathering annotations via ROADMAP server for: monocyte, brain"

## Warning in if (ROADMAP_search == "all_cell_types") {: the condition has
## length > 1 and only the first element will be used

## [1] "++ GoShifter: Searching for Roadmap annotation BED files..."
## [1] "++ GoShifter: Found 15 annotation BED files matching search query."
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E053_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E054_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E067_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E068_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E069_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E070_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E071_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E072_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E073_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E074_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E081_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E082_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E124_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E125_TssA_subset.bed.gz"
## [1] "+++ GoShifter:: Importing Previously downloaded BED subset: ./echolocatoR/tools/Annotations/ROADMAP/Chromatin_Marks/E029_TssA_subset.bed.gz"
## [1] "++ PAINTOR:: Merging and formatting BED files using PAINTOR utility."
## [1] "+++ PAINTOR:: Decompressing BED files."
## [1] "+++ PAINTOR:: Writing annotations paths file to  ==>  ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR/annotation_paths.txt"
## [1] "+++ PAINTOR:: Annotation--SNP overlap summaries:"
## [1] "+++ PAINTOR:: Removing temporary decompressed BED files."
## [1] "+ PAINTOR:: Preparing input.files"
## [1] "+ PAINTOR:: Running PAINTOR..."
## [1] "./echolocatoR/tools/PAINTOR_V3.0/PAINTOR -input ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR/input.files -Zhead ZSCORE.P1,ZSCORE.P2,ZSCORE.P3,ZSCORE.P4,ZSCORE.P5 -LDname ld1,ld1,ld1,ld1,ld1 -mcmc -in ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR -out ./Data/GWAS/Nalls23andMe_2019/LRRK2/PAINTOR -Gname Enrichment.Estimates.txt -RESname results.txt -ANname annotations.txt -set_seed 2019"

createDT(PAINTOR_results.FF)

QTL Boxplots

Fairfax eQTL

Below we take several SNPs of interest within the LRRK2 PD-associated locus:
- The 2 lead GWAS SNPs identified in Nalls et al. (2019).
- The Consensus SNP identified through the statistical fine-mapping pipeline.
We then identify whether any of them have eQTLs in the Fairfax et al. (2014) summary statistics.
- Fairfax, Benjamin P., Peter Humburg, Seiko Makino, Vivek Naranbhai, Daniel Wong, Evelyn Lau, Luke Jostins, et al. “Innate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression.” Science 343, no. 6175 (2014). https://doi.org/10.1126/science.1246949.

# snp_list <- subset(merged_results, Gene=="LRRK2")$SNP %>% unique()
snp_list <- c("rs7294519", "rs11175620", "rs76904798")

merged_eQTL_data <- eQTL_boxplots(snp_list,
             eQTL_SS_paths = file.path("Data/eQTL/Fairfax_2014",
                                       c("CD14/LRRK2/LRRK2_Fairfax_CD14.txt",
                                         "IFN/LRRK2/LRRK2_Fairfax_IFN.txt",
                                         "LPS2/LRRK2/LRRK2_Fairfax_LPS2.txt",
                                         "LPS24/LRRK2/LRRK2_Fairfax_LPS24.txt")),
             expression_paths = file.path("Data/eQTL/Fairfax_2014",
                                          c("CD14/CD14.47231.414.b.txt",
                                            "IFN/IFN.47231.367.b.txt",
                                            "LPS2/LPS2.47231.261.b.txt",
                                            "LPS24/LPS24.47231.322.b.txt")),
             genotype_path = "Data/eQTL/Fairfax_2014/geno.subset.txt",
             probe_path = "Data/eQTL/Fairfax_2014/gene.ILMN.map",
             .fam_path = "Data/eQTL/Fairfax_2014/volunteers_421.fam",
             gene = "LRRK2",
             show_plot = T,
             SS_annotations = F,
             interact = F)

## [1] ""
## [1] "+ Processsing Expression data"
## [1] "++ Extracting probe info"
## [1] "++ CD14"
## [1] "++ IFN"
## [1] "++ LPS2"
## [1] "++ LPS24"
## [1] ""
## [1] "+ Processing Summary Stats data"
## [1] ""
## [1] "+ Processing Genotype data"
## [1] ""
## [1] "+ Merging Summary Stats, Genotype, and Expression data"
## [1] "++ Splitting and writing merged files to storage..."
## [1] "+++ Data/eQTL/Fairfax_2014/CD14/LRRK2/LRRK2_CD14_subset.txt"
## [1] "+++ Data/eQTL/Fairfax_2014/IFN/LRRK2/LRRK2_IFN_subset.txt"
## [1] "+++ Data/eQTL/Fairfax_2014/LPS2/LRRK2/LRRK2_LPS2_subset.txt"
## [1] "+++ Data/eQTL/Fairfax_2014/LPS24/LRRK2/LRRK2_LPS24_subset.txt"
## [1] ""
## [1] "+ Plotting eQTLs"

Colocalization

Colocalization: MESA

Colocalization: Fairfax

Summarize

Fine-mapping eQTLs

AFR = AFA = African
AMR = Ad Mixed American
EAS = East Asian
EUR = CAU = European
SAS = South Asian
HIS = Hispanic

MESA

Fairfax (2014)

Use the Nalls et al. (2019) LRRK2 locus to query for SNPs in the eQTL data.
SS Files are SPACE-delimited (not tab-delimited)

Session Information

sessionInfo()

## R version 3.6.1 (2019-07-05)
## Platform: x86_64-apple-darwin15.6.0 (64-bit)
## Running under: macOS Mojave 10.14.5
## 
## Matrix products: default
## BLAS:   /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRblas.0.dylib
## LAPACK: /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRlapack.dylib
## 
## locale:
## [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
## 
## attached base packages:
## [1] stats     graphics  grDevices utils     datasets  methods   base     
## 
## other attached packages:
##  [1] biomaRt_2.40.3     BiocManager_1.30.4 tidyr_0.8.3       
##  [4] gaston_1.5.5       RcppParallel_4.4.3 Rcpp_1.0.2        
##  [7] curl_4.0           ggrepel_0.8.1      plotly_4.9.0      
## [10] ggplot2_3.2.1      dplyr_0.8.3        data.table_1.12.2 
## [13] readxl_1.3.1       devtools_2.1.0     usethis_1.5.1     
## [16] R.utils_2.9.0      R.oo_1.22.0        R.methodsS3_1.7.1 
## 
## loaded via a namespace (and not attached):
##  [1] bitops_1.0-6         fs_1.3.1             bit64_0.9-7         
##  [4] progress_1.2.2       httr_1.4.1           rprojroot_1.3-2     
##  [7] tools_3.6.1          backports_1.1.4      R6_2.4.0            
## [10] DT_0.8               DBI_1.0.0            lazyeval_0.2.2      
## [13] BiocGenerics_0.30.0  colorspace_1.4-1     withr_2.1.2         
## [16] tidyselect_0.2.5     prettyunits_1.0.2    processx_3.4.1      
## [19] bit_1.1-14           compiler_3.6.1       cli_1.1.0           
## [22] Biobase_2.44.0       desc_1.2.0           labeling_0.3        
## [25] scales_1.0.0         callr_3.3.1          stringr_1.4.0       
## [28] digest_0.6.20        rmarkdown_1.14       pkgconfig_2.0.2     
## [31] htmltools_0.3.6      sessioninfo_1.1.1    htmlwidgets_1.3     
## [34] rlang_0.4.0          RSQLite_2.1.2        shiny_1.3.2         
## [37] jsonlite_1.6         crosstalk_1.0.0      RCurl_1.95-4.12     
## [40] magrittr_1.5         munsell_0.5.0        S4Vectors_0.22.0    
## [43] stringi_1.4.3        yaml_2.2.0           plyr_1.8.4          
## [46] pkgbuild_1.0.4       grid_3.6.1           blob_1.2.0          
## [49] parallel_3.6.1       promises_1.0.1       crayon_1.3.4        
## [52] hms_0.5.0            zeallot_0.1.0        knitr_1.24          
## [55] ps_1.3.0             pillar_1.4.2         reshape2_1.4.3      
## [58] stats4_3.6.1         pkgload_1.0.2        XML_3.98-1.20       
## [61] glue_1.3.1           evaluate_0.14        remotes_2.1.0       
## [64] vctrs_0.2.0          httpuv_1.5.1         testthat_2.2.1      
## [67] cellranger_1.1.0     gtable_0.3.0         purrr_0.3.2         
## [70] assertthat_0.2.1     xfun_0.8             mime_0.7            
## [73] xtable_1.8-4         later_0.8.0          viridisLite_0.3.0   
## [76] tibble_2.1.3         AnnotationDbi_1.46.0 memoise_1.1.0       
## [79] IRanges_2.18.1

print(paste("susieR ", packageVersion("susieR")))

## [1] "susieR  0.8.1.521"

Functional Fine-mapping

Brian M. Schilder, Bioinformatician II
Raj Lab
Department of Neuroscience
Icahn School of Medicine at Mount Sinai
NYC, New York

RAJ LAB

Brian M. Schilder, Bioinformatician II
Raj Lab
Department of Neuroscience
Icahn School of Medicine at Mount Sinai
NYC, New York

Most Recent Update:
2019-08-23

PAINTOR

GWAS only

GWAS + Epigenetic Annotations

GWAS + Fairfax eQTLs + Epigenetic Annotations

QTL Boxplots

Fairfax eQTL

Colocalization

Colocalization: MESA

Colocalization: Fairfax

Summarize

Fine-mapping eQTLs

MESA

Fairfax (2014)

Session Information

Functional Fine-mapping

Brian M. Schilder, Bioinformatician II Raj Lab Department of Neuroscience Icahn School of Medicine at Mount Sinai NYC, New York RAJ LAB

Brian M. Schilder, Bioinformatician II Raj Lab Department of Neuroscience Icahn School of Medicine at Mount Sinai NYC, New York

Most Recent Update: 2019-08-23

PAINTOR

GWAS only

GWAS + Epigenetic Annotations

GWAS + Fairfax eQTLs + Epigenetic Annotations

QTL Boxplots

Fairfax eQTL

Colocalization

Colocalization: MESA

Colocalization: Fairfax

Summarize

Fine-mapping eQTLs

MESA

Fairfax (2014)

Session Information

Brian M. Schilder, Bioinformatician II
Raj Lab
Department of Neuroscience
Icahn School of Medicine at Mount Sinai
NYC, New York

RAJ LAB

Brian M. Schilder, Bioinformatician II
Raj Lab
Department of Neuroscience
Icahn School of Medicine at Mount Sinai
NYC, New York

Most Recent Update:
2019-08-23