Last updated: 2020-08-21
Checks: 5 1
Knit directory: ChromatinSplicingQTLs/analysis/
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This analysis is an example to demonstrate how I will set up Rmarkdowns for this project. See about for more description. In this example I will make a QQ-plot of H3K4me3 P-values (from Gruber et al), grouped by whether the SNP is an eQTL ( GEUVADIS data ). In the code
directory, the snakemake has already downloaded and or processed the data from these publications. I expect that SNPs that are eQTLs will have smaller P-values for H3K4me3.
First load necessary libraries and read in data…
library(tidyverse)
── Attaching packages ────────────────────────────────────────────────────── tidyverse 1.3.0 ──
✔ ggplot2 3.2.1 ✔ purrr 0.3.4
✔ tibble 2.1.3 ✔ dplyr 0.8.3
✔ tidyr 1.1.0 ✔ stringr 1.4.0
✔ readr 1.3.1 ✔ forcats 0.4.0
── Conflicts ───────────────────────────────────────────────────────── tidyverse_conflicts() ──
✖ dplyr::filter() masks stats::filter()
✖ dplyr::lag() masks stats::lag()
library(knitr)
Grubert.H3K4me3.QTLs <- read.delim("../code/PlotGruberQTLs/Data/localQTLs_H3K4ME3.FDR0.1.hg38.bedpe", col.names=c("SNP_chr", "SNP_pos", "SNP_stop", "Peak_Chr", "Peak_start", "Peak_stop", "Name", "Score", "strand1", "stand2"), stringsAsFactors = F) %>%
separate(col = "Name", into=c("PEAKid","SNPrsid","beta","p.value","FDR_TH","pvalTH","pass.pvalTH","mod","peak.state"), sep = ";", convert = T) %>%
mutate(SNP_pos = as.numeric(SNP_pos))
head(Grubert.H3K4me3.QTLs) %>% kable()
SNP_chr | SNP_pos | SNP_stop | Peak_Chr | Peak_start | Peak_stop | PEAKid | SNPrsid | beta | p.value | FDR_TH | pvalTH | pass.pvalTH | mod | peak.state | Score | strand1 | stand2 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
chr10 | 98266058 | 98266059 | chr10 | 98267895 | 98268846 | 1 | rs10748723 | 0.2032748 | 0.2292467 | 0.1 | 0.0009998 | fail | H3K4ME3 | TSS | . | . | . |
chr10 | 98268012 | 98268013 | chr10 | 98267895 | 98268846 | 1 | rs10786407 | -0.1114408 | 0.6567359 | 0.1 | 0.0009998 | fail | H3K4ME3 | TSS | . | . | . |
chr10 | 98268054 | 98268055 | chr10 | 98267895 | 98268846 | 1 | rs10883055 | -0.1188379 | 0.6095054 | 0.1 | 0.0009998 | fail | H3K4ME3 | TSS | . | . | . |
chr10 | 98266369 | 98266370 | chr10 | 98267895 | 98268846 | 1 | rs11189529 | -0.6061942 | 0.0009072 | 0.1 | 0.0009998 | pass | H3K4ME3 | TSS | . | . | . |
chr10 | 98266356 | 98266357 | chr10 | 98267895 | 98268846 | 1 | rs114440225 | -0.2236145 | 0.5527621 | 0.1 | 0.0009998 | fail | H3K4ME3 | TSS | . | . | . |
chr10 | 98269803 | 98269804 | chr10 | 98267895 | 98268846 | 1 | rs1325500 | -0.5212768 | 0.0047903 | 0.1 | 0.0009998 | fail | H3K4ME3 | TSS | . | . | . |
GEUVADIS.eQTLs <- read.delim("../data/QTLBase.GEUVADIS.eQTLs.hg38.txt.gz", stringsAsFactors = F) %>%
mutate(SNP_chr=paste0("chr",SNP_chr)) %>%
filter(!SNP_chr == "chr6") %>% #blunt way to filter out MHC locus
mutate(SNP_pos = as.numeric(SNP_pos)) %>%
mutate(SNP=paste(SNP_chr, SNP_pos))
head(GEUVADIS.eQTLs) %>% kable()
SNP_chr | SNP_pos | Mapped_gene | Trait_chr | Trait_start | Trait_end | Pvalue | Sourceid | SNP |
---|---|---|---|---|---|---|---|---|
chr4 | 76939335 | NAAA | 4 | 76834813 | 76862166 | 0.0e+00 | 418 | chr4 76939335 |
chr4 | 76939335 | CXCL10 | 4 | 76942271 | 76944650 | 0.0e+00 | 418 | chr4 76939335 |
chr4 | 144902942 | GYPE | 4 | 144792017 | 144826716 | 0.0e+00 | 418 | chr4 144902942 |
chr4 | 83899764 | SCD5 | 4 | 83550692 | 83719949 | 0.0e+00 | 418 | chr4 83899764 |
chr4 | 88310523 | HSD17B11 | 4 | 88257667 | 88312340 | 3.1e-06 | 418 | chr4 88310523 |
chr4 | 84144189 | PLAC8 | 4 | 84011201 | 84058228 | 1.0e-07 | 418 | chr4 84144189 |
Peruse data a little.
hist(Grubert.H3K4me3.QTLs$p.value)
Ok, good look histogram of P-values for H3K4me3 QTLs. What about eQTLs from GEUVADIS which I downlaoded from QTLbase
hist(GEUVADIS.eQTLs$Pvalue)
Ok.. those P-values are all very very small. It seems the P values from QTLbase are only for significant eQTLs. So now let’s make a QQ-plot for H3K4me3 QTL P-values, based on whether the snp is an eQTL.
H3K4me3_QQ <- Grubert.H3K4me3.QTLs %>%
dplyr::select(p.value, SNP_chr, SNP_chr, SNP_pos) %>%
filter(!SNP_chr == "chr6") %>%
mutate(SNP=paste(SNP_chr, SNP_pos)) %>%
mutate(SNPIsEqtl= SNP %in% GEUVADIS.eQTLs$SNP) %>%
group_by(SNPIsEqtl) %>%
mutate(ExpectedP=percent_rank(p.value)) %>%
sample_n(400) %>% #Just sample 400 random points from each group to be quick
ggplot(aes(x=-log10(ExpectedP), y=-log10(p.value), color=SNPIsEqtl)) +
geom_point() +
geom_abline() +
theme_bw()
H3K4me3_QQ
As expected, SNPs that are eQTLs have more significant P-value inflation for H3K4me3 genetic effects.
sessionInfo()
R version 3.6.1 (2019-07-05)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Scientific Linux 7.4 (Nitrogen)
Matrix products: default
BLAS/LAPACK: /software/openblas-0.2.19-el7-x86_64/lib/libopenblas_haswellp-r0.2.19.so
locale:
[1] LC_CTYPE=en_US.UTF-8 LC_NUMERIC=C
[3] LC_TIME=en_US.UTF-8 LC_COLLATE=en_US.UTF-8
[5] LC_MONETARY=en_US.UTF-8 LC_MESSAGES=en_US.UTF-8
[7] LC_PAPER=en_US.UTF-8 LC_NAME=C
[9] LC_ADDRESS=C LC_TELEPHONE=C
[11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C
attached base packages:
[1] stats graphics grDevices utils datasets methods base
other attached packages:
[1] knitr_1.23 forcats_0.4.0 stringr_1.4.0 dplyr_0.8.3
[5] purrr_0.3.4 readr_1.3.1 tidyr_1.1.0 tibble_2.1.3
[9] ggplot2_3.2.1 tidyverse_1.3.0
loaded via a namespace (and not attached):
[1] tidyselect_1.1.0 xfun_0.8 haven_2.3.1 lattice_0.20-38
[5] colorspace_1.4-1 vctrs_0.3.1 generics_0.0.2 htmltools_0.3.6
[9] yaml_2.2.0 rlang_0.4.6 later_0.8.0 pillar_1.4.2
[13] withr_2.1.2 glue_1.3.1 DBI_1.1.0 dbplyr_1.4.2
[17] modelr_0.1.8 readxl_1.3.1 lifecycle_0.1.0 munsell_0.5.0
[21] gtable_0.3.0 workflowr_1.6.2 cellranger_1.1.0 rvest_0.3.5
[25] evaluate_0.14 labeling_0.3 httpuv_1.5.1 highr_0.8
[29] broom_0.5.2 Rcpp_1.0.3 promises_1.0.1 backports_1.1.4
[33] scales_1.1.0 jsonlite_1.6 farver_2.0.1 fs_1.3.1
[37] hms_0.5.3 digest_0.6.20 stringi_1.4.3 grid_3.6.1
[41] rprojroot_1.3-2 cli_1.1.0 tools_3.6.1 magrittr_1.5
[45] lazyeval_0.2.2 crayon_1.3.4 pkgconfig_2.0.2 ellipsis_0.2.0.1
[49] xml2_1.3.2 reprex_0.3.0 lubridate_1.7.4 rstudioapi_0.10
[53] assertthat_0.2.1 rmarkdown_1.13 httr_1.4.1 R6_2.4.0
[57] nlme_3.1-140 git2r_0.26.1 compiler_3.6.1