Last updated: 2022-07-02
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Knit directory: Serreze-T1D_Workflow/
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Unstaged changes:
Modified: analysis/4.1.1_qtl.analysis_binary_ici-early.vs.pbs_5.batches.Rmd
Modified: analysis/4.1.1_qtl.analysis_binary_ici-early.vs.pbs_5.batches_mis.Rmd
Modified: analysis/4.1.1_qtl.analysis_binary_ici-early.vs.pbs_snpsqc_5.batches.Rmd
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Modified: analysis/4.1.1_qtl.analysis_binary_ici-early.vs.pbs_snpsqc_dis_no-x_updated_5.batches.Rmd
Modified: analysis/4.1.1_qtl.analysis_binary_ici-early.vs.pbs_snpsqc_dis_no-x_updated_5.batches_mis.Rmd
Modified: analysis/4.1.1_qtl.analysis_binary_ici.vs.eoi_snpsqc_dis_no-x_updated.Rmd
Modified: analysis/4.1.1_qtl.analysis_binary_ici.vs.pbs_snpsqc_dis_no-x_updated.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici-early.vs.pbs_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici-early.vs.pbs_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.eoi_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.eoi_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.eoi_snpsqc_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.eoi_snpsqc_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.eoi_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.eoi_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.pbs_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.pbs_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici-early.vs.pbs_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici-early.vs.pbs_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.eoi_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.eoi_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.eoi_snpsqc_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.eoi_snpsqc_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.eoi_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.eoi_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches_mis.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches.Rmd
Modified: analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches_mis.Rmd
Modified: analysis/genotype.frequencies_ici.vs.eoi_5.batches.Rmd
Modified: analysis/genotype.frequencies_ici.vs.eoi_5.batches_mis.Rmd
Modified: analysis/genotype.frequencies_ici.vs.pbs_5.batches.Rmd
Modified: analysis/genotype.frequencies_ici.vs.pbs_5.batches_mis.Rmd
Modified: analysis/index_5.batches.Rmd
Modified: analysis/index_5.batches_additional.Rmd
Note that any generated files, e.g. HTML, png, CSS, etc., are not included in this status report because it is ok for generated content to have uncommitted changes.
There are no past versions. Publish this analysis with
wflow_publish()
to start tracking its development.
We will load the data and subset indivials out that are in the groups of interest. We will create a binary phenotype from this (PBS ==0, ICI == 1).
load("data/gm_allqc_5.batches.RData")
#gm_allqc
gm=gm_allqc
gm
Object of class cross2 (crosstype "bc")
Total individuals 308
No. genotyped individuals 308
No. phenotyped individuals 308
No. with both geno & pheno 308
No. phenotypes 1
No. covariates 6
No. phenotype covariates 0
No. chromosomes 20
Total markers 34537
No. markers by chr:
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
2643 2629 1857 1890 1774 1941 1672 1627 1878 1176 1871 1300 1549 1578 1257 935
17 18 19 X
501 913 1014 4532
#pr <- readRDS("data/serreze_probs_allqc.rds")
#pr <- readRDS("data/serreze_probs.rds")
##extracting animals with ici and pbs group status
miceinfo <- gm$covar[gm$covar$group == "PBS" | gm$covar$group == "ICI",]
table(miceinfo$group)
ICI PBS
104 34
mice.ids <- rownames(miceinfo)
gm <- gm[mice.ids]
gm
Object of class cross2 (crosstype "bc")
Total individuals 138
No. genotyped individuals 138
No. phenotyped individuals 138
No. with both geno & pheno 138
No. phenotypes 1
No. covariates 6
No. phenotype covariates 0
No. chromosomes 20
Total markers 34537
No. markers by chr:
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
2643 2629 1857 1890 1774 1941 1672 1627 1878 1176 1871 1300 1549 1578 1257 935
17 18 19 X
501 913 1014 4532
#pr.qc <- pr
#for (i in 1:20){pr.qc[[i]] = pr.qc[[i]][mice.ids,,]}
#bin_pheno <- NULL
#bin_pheno$PBS <- ifelse(gm$covar$group == "PBS", 1, 0)
#bin_pheno$ICI <- ifelse(gm$covar$group == "ICI", 1, 0)
#bin_pheno <- as.data.frame(bin_pheno)
#rownames(bin_pheno) <- rownames(gm$covar)
gm$covar$ICI.vs.PBS <- ifelse(gm$covar$group == "PBS", 0, 1)
gm.full <- gm
##adding peaks as covariates: UNCHS008487, UNC8250659, UNC18240977
mar.covar <- pull_markers(gm, c("UNCHS008487", "UNC8250659", "UNC18240977"))
mar.covar.g <- do.call("cbind", mar.covar$geno)
covars <- merge(gm$covar, mar.covar.g, by='row.names', sort=F)
table(covars$group)
ICI PBS
104 34
rownames(covars) <- covars$Row.names
covars <- covars[-1]
##removing problmetic marker
gm <- drop_markers(gm, "UNCHS013106")
##dropping monomorphic markers within the dataset
g <- do.call("cbind", gm$geno)
gf_mar <- t(apply(g, 2, function(a) table(factor(a, 1:2))/sum(a != 0)))
#gn_mar <- t(apply(g, 2, function(a) table(factor(a, 1:2))))
gf_mar <- gf_mar[gf_mar[,2] != "NaN",]
count <- rowSums(gf_mar <=0.05)
low_freq_df <- merge(as.data.frame(gf_mar),as.data.frame(count), by="row.names",all=T)
low_freq_df[is.na(low_freq_df)] <- ''
low_freq_df <- low_freq_df[low_freq_df$count == 1,]
rownames(low_freq_df) <- low_freq_df$Row.names
low_freq <- find_markerpos(gm, rownames(low_freq_df))
low_freq$id <- rownames(low_freq)
nrow(low_freq)
[1] 7989
low_freq_bad <- merge(low_freq,low_freq_df, by="row.names",all=T)
names(low_freq_bad)[1] <- c("marker")
gf_mar <- gf_mar[gf_mar[,2] != "NaN",]
MAF <- apply(gf_mar, 1, function(x) min(x))
MAF <- as.data.frame(MAF)
MAF$index <- 1:nrow(gf_mar)
gf_mar_maf <- merge(gf_mar,as.data.frame(MAF), by="row.names")
gf_mar_maf <- gf_mar_maf[order(gf_mar_maf$index),]
gfmar <- NULL
gfmar$gfmar_mar_0 <- sum(gf_mar_maf$MAF==0)
gfmar$gfmar_mar_1 <- sum(gf_mar_maf$MAF< 0.01)
gfmar$gfmar_mar_5 <- sum(gf_mar_maf$MAF< 0.05)
gfmar$gfmar_mar_10 <- sum(gf_mar_maf$MAF< 0.10)
gfmar$gfmar_mar_15 <- sum(gf_mar_maf$MAF< 0.15)
gfmar$gfmar_mar_25 <- sum(gf_mar_maf$MAF< 0.25)
gfmar$gfmar_mar_50 <- sum(gf_mar_maf$MAF< 0.50)
gfmar$total_snps <- nrow(as.data.frame(gf_mar_maf))
gfmar <- t(as.data.frame(gfmar))
gfmar <- as.data.frame(gfmar)
gfmar$count <- gfmar$V1
gfmar[c(2)] %>%
kable(escape = F,align = c("ccccccccc"),linesep ="\\hline") %>%
kable_styling(full_width = F) %>%
kable_styling("striped", full_width = F) %>%
row_spec(8 ,bold=T,color= "white",background = "black")
count | |
---|---|
gfmar_mar_0 | 3814 |
gfmar_mar_1 | 4068 |
gfmar_mar_5 | 7989 |
gfmar_mar_10 | 8527 |
gfmar_mar_15 | 8598 |
gfmar_mar_25 | 9313 |
gfmar_mar_50 | 33753 |
total_snps | 34537 |
gm_qc <- drop_markers(gm, low_freq_bad$marker)
gm_qc <- drop_nullmarkers(gm_qc)
gm = gm_qc
gm
Object of class cross2 (crosstype "bc")
Total individuals 138
No. genotyped individuals 138
No. phenotyped individuals 138
No. with both geno & pheno 138
No. phenotypes 1
No. covariates 7
No. phenotype covariates 0
No. chromosomes 20
Total markers 26548
No. markers by chr:
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
2374 2374 1623 1691 1568 1703 1464 1468 1685 974 1671 1134 1377 1411 876 751
17 18 19 X
330 770 920 384
markers <- marker_names(gm)
gmapdf <- read.csv("/Users/corneb/Documents/MyJax/CS/Projects/Serreze/haplotype.reconstruction/output_5.batches/genetic_map.csv")
pmapdf <- read.csv("/Users/corneb/Documents/MyJax/CS/Projects/Serreze/haplotype.reconstruction/output_5.batches/physical_map.csv")
#mapdf <- merge(gmapdf,pmapdf, by=c("marker","chr"), all=T)
#rownames(mapdf) <- mapdf$marker
#mapdf <- mapdf[markers,]
#names(mapdf) <- c('marker','chr','gmapdf','pmapdf')
#mapdfnd <- mapdf[!duplicated(mapdf[c(2:3)]),]
pr.qc <- calc_genoprob(gm)
#gm
Xcovar <- get_x_covar(gm)
#addcovar = model.matrix(~Sex, data = covars)[,-1]
addcovar = model.matrix(~UNCHS008487, data = covars)[,-1]
#K <- calc_kinship(pr.qc, type = "loco")
#heatmap(K[[1]])
#K.overall <- calc_kinship(pr.qc, type = "overall")
#heatmap(K.overall)
kinship <- calc_kinship(pr.qc)
heatmap(kinship)
#operm <- scan1perm(pr.qc, gm$covar$phenos, Xcovar=Xcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, addcovar = addcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, n_perm=2000)
operm <- scan1perm(pr.qc, gm$covar["ICI.vs.PBS"], model="binary", n_perm=10, perm_Xsp=TRUE, chr_lengths=chr_lengths(gm$gmap), addcovar = addcovar)
summary_table<-data.frame(unclass(summary(operm, alpha=c(0.01, 0.05, 0.1))))
names(summary_table) <- c("autosomes","X")
summary_table$significance.level <- rownames(summary_table)
rownames(summary_table) <- NULL
summary_table[c(3,1:2)] %>%
kable(escape = F,align = c("ccc")) %>%
kable_styling("striped", full_width = T) %>%
column_spec(1, bold=TRUE)
significance.level | autosomes | X |
---|---|---|
0.01 | 2.728945 | 4.014186 |
0.05 | 2.674651 | 3.303588 |
0.1 | 2.606618 | 2.374305 |
The figures below show QTL maps for each phenotype
out <- scan1(pr.qc, gm$covar["ICI.vs.PBS"], Xcovar=Xcovar, model="binary", addcovar = addcovar)
summary_table<-data.frame(unclass(summary(operm, alpha=c(0.01, 0.05, 0.1))))
plot_lod<-function(out,map){
for (i in 1:dim(out)[2]){
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i], "_lod.png"))
ymx <- maxlod(out) # overall maximum LOD score
plot(out, map, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " [positions in cM]"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#par(mar=c(5.1, 6.1, 1.1, 1.1))
ymx <- 11 # overall maximum LOD score
plot(out, map, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " [positions in cM] \n(using same scale as eoi vs ici for easier comparison)"))
add_threshold(map, summary(operm, alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#for (j in 1: dim(summary_table)[1]){
# abline(h=summary_table[j, i],col="red")
# text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
#}
#dev.off()
}
}
plot_lod(out,gm$gmap)
The table below shows QTL peaks associated with the phenotype. We use the 95% threshold from the permutations to find peaks.
peaks <- find_peaks(out, gm$gmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, peakdrop=3, drop=1.5)
if(nrow(peaks) >0){
peaks$marker <- find_marker(gm$gmap, chr=peaks$chr,pos=peaks$pos)
names(peaks)[2] <- c("phenotype")
peaks <- peaks[-1]
rownames(peaks) <- NULL
#print(kable(peaks, "html")
# %>% kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
# )
print(kable(peaks, escape = F, align = c("cccccccc"), "html")
%>% kable_styling("striped", full_width = T)%>%
column_spec(1, bold=TRUE)
)
#peaks[] %>%
# kable(escape = F,align = c("cccccccc")) %>%
# kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
#plot only peak chromosomes
plot_lod_chr<-function(out,map,chrom){
for (i in 1:dim(out)[2]){
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i], "_lod.png"))
#par(mar=c(5.1, 6.1, 1.1, 1.1))
ymx <- maxlod(out) # overall maximum LOD score
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in cM]"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#for (j in 1: dim(summary_table)[1]){
# abline(h=summary_table[j, i],col="red")
# text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
#}
#dev.off()
ymx <- 11
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in cM]\n(using same scale as eoi vs. ici for easier comparison)"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
}
}
for(i in unique(peaks$chr)){
#for (i in 1:nrow(peaks)){
#plot_lod_chr(out,gm$gmap, peaks$chr[i])
plot_lod_chr(out,gm$gmap, i)
}
} else {
print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}
[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.67465122006504 [autosomes]/3.30358811059369 [x-chromosome]”
print("peaks in MB positions")
[1] “peaks in MB positions”
peaks_mba <- find_peaks(out, gm$pmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, peakdrop=3, drop=1.5)
if(nrow(peaks) >0){
peaks_mba$marker <- find_marker(gm$pmap, chr=peaks_mba$chr,pos=peaks_mba$pos)
names(peaks_mba)[2] <- c("phenotype")
peaks_mba <- peaks_mba[-1]
#peaks_mbl <- list()
##corresponding info in Mb
#for(i in 1:nrow(peaks)){
# #lodindex <- peaks$lodindex[i]
# phenotype <- peaks$phenotype[i]
# chr <- as.character(peaks$chr[i])
# lod <- peaks$lod[i]
# mark <- peaks$marker[i]
# pos <- mapdf[mapdf$marker==mark,]$pmapdf
# ci_lo <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_lo[i] & mapdfnd$chr == peaks$chr[i])]
# ci_hi <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_hi[i] & mapdfnd$chr == peaks$chr[i])]
# peaks_mb=as.data.frame(cbind(phenotype, chr, pos, lod, ci_lo, ci_hi, mark))
# names(peaks_mb)[7] <- c("marker")
# peaks_mbl[[i]] <- peaks_mb
#}
#peaks_mba2 <- do.call(rbind, peaks_mbl)
#peaks_mba2 <- as.data.frame(peaks_mba)
#peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")] <- sapply(peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")], as.numeric)
rownames(peaks_mba) <- NULL
#print(kable(peaks_mba, "html")
# %>% kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
# )
print(kable(peaks_mba, escape = F, align = c("cccccccc"), "html")
%>% kable_styling("striped", full_width = T)%>%
column_spec(1, bold=TRUE)
)
#peaks_mba[] %>%
# kable(escape = F,align = c("cccccccc")) %>%
# kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
plot_lod_chr_mb<-function(out,map,chrom){
for (i in 1:dim(out)[2]){
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i], "_lod.png"))
#par(mar=c(5.1, 6.1, 1.1, 1.1))
ymx <- maxlod(out) # overall maximum LOD score
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in MB]"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#for (j in 1: dim(summary_table)[1]){
# abline(h=summary_table[j, i],col="red")
# text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
#}
#dev.off()
ymx <- 11
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in MB]\n(using same scale as eoi vs. ici for easier comparison)"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
}
}
for(i in unique(peaks_mba$chr)){
#for (i in 1:nrow(peaks_mba)){
#plot_lod_chr_mb(out,gm$pmap, peaks_mba$chr[i])
plot_lod_chr_mb(out,gm$pmap,i)
}
} else {
print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}
[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.67465122006504 [autosomes]/3.30358811059369 [x-chromosome]”
For each peak LOD location we give a list of gene
query_variants <- create_variant_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/cc_variants.sqlite")
query_genes <- create_gene_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/mouse_genes_mgi.sqlite")
if(nrow(peaks) >0){
for (i in 1:nrow(peaks)){
#for (i in 1:1){
#Plot 1
#marker = find_marker(gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i])
#gp <- g[,marker]
#gp[gp==1] <- "AA"
#gp[gp==2] <- "AB"
#gp[gp==0] <- NA
#plot_pxg(gp, gm$covar[,peaks$phenotype[i]], ylab=peaks$phenotype[i], sort=FALSE)
#title(main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i]," )"), line=0.2)
###dev.off()
g <- maxmarg(pr.qc, gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i], return_char=TRUE)
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/","qtl_effect_", i, ".png"))
#par(mar=c(4.1, 4.1, 1.5, 0.6))
plot_pxg(g, gm$covar[,peaks$phenotype[i]], ylab=peaks$phenotype[i], sort=FALSE)
title(main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i]," )"), line=0.2)
##dev.off()
chr = peaks$chr[i]
# Plot 2
pr_sub <- pull_genoprobint(pr.qc, gm$gmap, chr, c(peaks$ci_lo[i], peaks$ci_hi[i]))
#coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar)
#coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], Xcovar=Xcovar)
#coeff <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
#coeff_sub <- scan1coef(pr_sub[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
blup <- scan1blup(pr.qc[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)
blup_sub <- scan1blup(pr_sub[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)
write.csv(as.data.frame(blup_sub), paste0("data/ici.vs.pbs_blup_sub_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr3.csv"), quote=F)
#plot_coef(coeff,
# gm$gmap, columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i]," [scan1coeff; positions in cM])")
# )
#plot_coef(coeff_sub,
# gm$gmap, columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i],"; 1.5 LOD drop interval [scan1coeff; positions in cM] ) ")
# )
plot_coef(blup,
gm$gmap, columns=1:2,
bgcolor="gray95", legend="bottomleft",
main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i]," [scan1blup; positions in cM])")
)
plot_coef(blup_sub,
gm$gmap, columns=1:2,
bgcolor="gray95", legend="bottomleft",
main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i],"; 1.5 LOD drop interval [scan1blup; positions in cM])")
)
# Plot 3
#c2effB <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary", contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
#c2effBb <- scan1blup(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]],Xcovar=Xcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
#plot(c2effB, gm$gmap[chr], columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
# )
#plot(c2effBb, gm$gmap[chr], columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
# )
##last_coef <- unclass(c2effB)[nrow(c2effB),2:3] # last two coefficients
##for(t in seq(along=last_coef))
## axis(side=4, at=last_coef[t], names(last_coef)[t], tick=FALSE)
#Table 1
chr = peaks_mba$chr[i]
start=as.numeric(peaks_mba$ci_lo[i])
end=as.numeric(peaks_mba$ci_hi[i])
genesgss = query_genes(chr, start, end)
write.csv(genesgss, file=paste0("data/ici.vs.pbs_genes_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr3.csv"), quote=F)
rownames(genesgss) <- NULL
genesgss$strand_old = genesgss$strand
genesgss$strand[genesgss$strand=="+"] <- "positive"
genesgss$strand[genesgss$strand=="-"] <- "negative"
#genesgss <-
#table <-
#genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")] %>%
#kable(escape = F,align = c("ccccccccccc")) %>%
#kable_styling("striped", full_width = T) #%>%
#cat #%>%
#column_spec(1, bold=TRUE)
#
#print(kable(genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")], escape = F,align = c("ccccccccccc")))
print(kable(genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")], "html") %>% kable_styling("striped", full_width = T))
}
} else {
print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}
[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.67465122006504 [autosomes]/3.30358811059369 [x-chromosome]”
gm
Object of class cross2 (crosstype "bc")
Total individuals 138
No. genotyped individuals 138
No. phenotyped individuals 138
No. with both geno & pheno 138
No. phenotypes 1
No. covariates 7
No. phenotype covariates 0
No. chromosomes 20
Total markers 26548
No. markers by chr:
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
2374 2374 1623 1691 1568 1703 1464 1468 1685 974 1671 1134 1377 1411 876 751
17 18 19 X
330 770 920 384
#detach("package:qtl2", unload=TRUE)
#library(qtl)
cross <- qtl::read.cross("csv", file = "data/ici.vs.pbs_gm_qtl_snpsqc_5.batches_mis_conditional_1-peak-chr3.csv",alleles=c("A","B"))
--Read the following data:
138 individuals
26548 markers
4 phenotypes
--Cross type: bc
cross <- qtl::jittermap(cross)
summary(cross)
Backcross
No. individuals: 138
No. phenotypes: 4
Percent phenotyped: 100 100 100 100
No. chromosomes: 20
Autosomes: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
X chr: X
Total markers: 26548
No. markers: 2374 2374 1623 1691 1568 1703 1464 1468 1685 974 1671
1134 1377 1411 876 751 330 770 920 384
Percent genotyped: 99.5
Genotypes (%):
Autosomes: AA:54.4 AB:45.6
X chromosome: AA:53.3 AB:46.7
cross.probs <- qtl::calc.genoprob(cross)
print("method == hk")
[1] "method == hk"
add.covars = qtl::pull.pheno(cross.probs, c("UNCHS008487"))
scanone.hk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="hk", addcovar = add.covars)
operm.hk <- qtl::scanone(cross.probs, method = "hk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE, addcovar = add.covars)
plot(operm.hk)
print(summary(operm.hk, alpha=c(0.01, 0.05, 0.1)))
Autosome LOD thresholds (10 permutations)
lod
1% 3.87
5% 3.37
10% 2.75
X chromosome LOD thresholds (186 permutations)
lod
1% 3.24
5% 3.05
10% 2.79
#plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")
#qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.1, col = 'purple')
ymx <- maxlod(out) # overall maximum LOD score
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]"))
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.1, col = 'purple')
ymx <- 11
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]\n(using same scale as eoi vs ici for easier comparison)"))
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.1, col = 'purple')
print(as.data.frame(summary(scanone.hk, perms=operm.hk, pvalues=TRUE, format="allpeaks")))
chr pos lod pval
UNC163443 1 4.774075 1.3742470 1.0000000
UNC2987704 2 27.689343 0.8724495 1.0000000
JAX00521745 3 20.613263 0.7585338 1.0000000
JAX00556948 4 41.038578 0.7729973 1.0000000
JAX00585101 5 36.216736 0.8544324 1.0000000
UNC10923091 6 18.321248 0.7018820 1.0000000
JAX00657315 7 81.940339 0.7731087 1.0000000
UNCHS023364 8 35.540812 1.5630473 0.9116914
UNCHS026281 9 40.415965 0.5497421 1.0000000
UNCHS028001 10 21.783253 1.0219015 1.0000000
UNCHS030712 11 32.135777 0.8396617 1.0000000
UNC21787084 12 53.288083 0.7631460 1.0000000
UNC22384241 13 13.831342 1.6038654 0.9116914
UNCHS038350 14 30.005599 0.4749227 1.0000000
UNC25285746 15 12.031111 0.8983676 1.0000000
UNC26465114 16 13.431084 0.7730271 1.0000000
JAX00077123 17 31.150016 0.7729946 1.0000000
UNC29709766 18 55.191705 0.5543284 1.0000000
UNC29893228 19 8.029054 1.6298590 0.8166471
JAX00176908 X 4.172023 0.7731463 0.9999998
print("all peaks with a p-value less or equal to 0.05 (suggestive)")
[1] "all peaks with a p-value less or equal to 0.05 (suggestive)"
print(as.data.frame(summary(scanone.hk, perms=operm.hk, alpha=0.05, pvalues=TRUE, format="allpeaks")))
[1] chr pos lod
<0 rows> (or 0-length row.names)
#print("method == ehk")
#scanone.ehk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="ehk")
#operm.ehk <- qtl::scanone(cross.probs, method = "ehk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE)
#plot(operm.ehk)
#print(summary(operm.ehk, alpha=c(0.01, 0.05, 0.1)))
#plot(scanone.ehk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")
#qtl::add.threshold(scanone.ehk, perms= operm.ehk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.ehk, perms= operm.ehk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.ehk, perms= operm.ehk, alpha=0.1, col = 'purple')
#print(as.data.frame(summary(scanone.ehk)))
#print(as.data.frame(summary(scanone.ehk, perms=operm.ehk, alpha=0.05, pvalues=TRUE, format="allpeaks")))
#gm
Xcovar <- get_x_covar(gm)
#addcovar = model.matrix(~Sex, data = covars)[,-1]
addcovar = model.matrix(~UNC8250659, data = covars)[,-1]
#K <- calc_kinship(pr.qc, type = "loco")
#heatmap(K[[1]])
#K.overall <- calc_kinship(pr.qc, type = "overall")
#heatmap(K.overall)
kinship <- calc_kinship(pr.qc)
heatmap(kinship)
#operm <- scan1perm(pr.qc, gm$covar$phenos, Xcovar=Xcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, addcovar = addcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, n_perm=2000)
operm <- scan1perm(pr.qc, gm$covar["ICI.vs.PBS"], model="binary", n_perm=10, perm_Xsp=TRUE, chr_lengths=chr_lengths(gm$gmap), addcovar = addcovar)
summary_table<-data.frame(unclass(summary(operm, alpha=c(0.01, 0.05, 0.1))))
names(summary_table) <- c("autosomes","X")
summary_table$significance.level <- rownames(summary_table)
rownames(summary_table) <- NULL
summary_table[c(3,1:2)] %>%
kable(escape = F,align = c("ccc")) %>%
kable_styling("striped", full_width = T) %>%
column_spec(1, bold=TRUE)
significance.level | autosomes | X |
---|---|---|
0.01 | 2.997095 | 2.614432 |
0.05 | 2.720357 | 2.589449 |
0.1 | 2.373590 | 2.556779 |
The figures below show QTL maps for each phenotype
out <- scan1(pr.qc, gm$covar["ICI.vs.PBS"], Xcovar=Xcovar, model="binary", addcovar = addcovar)
summary_table<-data.frame(unclass(summary(operm, alpha=c(0.01, 0.05, 0.1))))
plot_lod<-function(out,map){
for (i in 1:dim(out)[2]){
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i], "_lod.png"))
ymx <- maxlod(out) # overall maximum LOD score
plot(out, map, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " [positions in cM]"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#par(mar=c(5.1, 6.1, 1.1, 1.1))
ymx <- 11 # overall maximum LOD score
plot(out, map, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " [positions in cM] \n(using same scale as eoi vs ici for easier comparison)"))
add_threshold(map, summary(operm, alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#for (j in 1: dim(summary_table)[1]){
# abline(h=summary_table[j, i],col="red")
# text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
#}
#dev.off()
}
}
plot_lod(out,gm$gmap)
The table below shows QTL peaks associated with the phenotype. We use the 95% threshold from the permutations to find peaks.
peaks <- find_peaks(out, gm$gmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, peakdrop=3, drop=1.5)
if(nrow(peaks) >0){
peaks$marker <- find_marker(gm$gmap, chr=peaks$chr,pos=peaks$pos)
names(peaks)[2] <- c("phenotype")
peaks <- peaks[-1]
rownames(peaks) <- NULL
#print(kable(peaks, "html")
# %>% kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
# )
print(kable(peaks, escape = F, align = c("cccccccc"), "html")
%>% kable_styling("striped", full_width = T)%>%
column_spec(1, bold=TRUE)
)
#peaks[] %>%
# kable(escape = F,align = c("cccccccc")) %>%
# kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
#plot only peak chromosomes
plot_lod_chr<-function(out,map,chrom){
for (i in 1:dim(out)[2]){
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i], "_lod.png"))
#par(mar=c(5.1, 6.1, 1.1, 1.1))
ymx <- maxlod(out) # overall maximum LOD score
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in cM]"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#for (j in 1: dim(summary_table)[1]){
# abline(h=summary_table[j, i],col="red")
# text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
#}
#dev.off()
ymx <- 11
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in cM]\n(using same scale as eoi vs. ici for easier comparison)"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
}
}
for(i in unique(peaks$chr)){
#for (i in 1:nrow(peaks)){
#plot_lod_chr(out,gm$gmap, peaks$chr[i])
plot_lod_chr(out,gm$gmap, i)
}
} else {
print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}
[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.72035707026121 [autosomes]/2.58944938717251 [x-chromosome]”
print("peaks in MB positions")
[1] “peaks in MB positions”
peaks_mba <- find_peaks(out, gm$pmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, peakdrop=3, drop=1.5)
if(nrow(peaks) >0){
peaks_mba$marker <- find_marker(gm$pmap, chr=peaks_mba$chr,pos=peaks_mba$pos)
names(peaks_mba)[2] <- c("phenotype")
peaks_mba <- peaks_mba[-1]
#peaks_mbl <- list()
##corresponding info in Mb
#for(i in 1:nrow(peaks)){
# #lodindex <- peaks$lodindex[i]
# phenotype <- peaks$phenotype[i]
# chr <- as.character(peaks$chr[i])
# lod <- peaks$lod[i]
# mark <- peaks$marker[i]
# pos <- mapdf[mapdf$marker==mark,]$pmapdf
# ci_lo <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_lo[i] & mapdfnd$chr == peaks$chr[i])]
# ci_hi <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_hi[i] & mapdfnd$chr == peaks$chr[i])]
# peaks_mb=as.data.frame(cbind(phenotype, chr, pos, lod, ci_lo, ci_hi, mark))
# names(peaks_mb)[7] <- c("marker")
# peaks_mbl[[i]] <- peaks_mb
#}
#peaks_mba2 <- do.call(rbind, peaks_mbl)
#peaks_mba2 <- as.data.frame(peaks_mba)
#peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")] <- sapply(peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")], as.numeric)
rownames(peaks_mba) <- NULL
#print(kable(peaks_mba, "html")
# %>% kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
# )
print(kable(peaks_mba, escape = F, align = c("cccccccc"), "html")
%>% kable_styling("striped", full_width = T)%>%
column_spec(1, bold=TRUE)
)
#peaks_mba[] %>%
# kable(escape = F,align = c("cccccccc")) %>%
# kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
plot_lod_chr_mb<-function(out,map,chrom){
for (i in 1:dim(out)[2]){
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i], "_lod.png"))
#par(mar=c(5.1, 6.1, 1.1, 1.1))
ymx <- maxlod(out) # overall maximum LOD score
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in MB]"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#for (j in 1: dim(summary_table)[1]){
# abline(h=summary_table[j, i],col="red")
# text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
#}
#dev.off()
ymx <- 11
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in MB]\n(using same scale as eoi vs. ici for easier comparison)"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
}
}
for(i in unique(peaks_mba$chr)){
#for (i in 1:nrow(peaks_mba)){
#plot_lod_chr_mb(out,gm$pmap, peaks_mba$chr[i])
plot_lod_chr_mb(out,gm$pmap,i)
}
} else {
print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}
[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.72035707026121 [autosomes]/2.58944938717251 [x-chromosome]”
For each peak LOD location we give a list of gene
query_variants <- create_variant_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/cc_variants.sqlite")
query_genes <- create_gene_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/mouse_genes_mgi.sqlite")
if(nrow(peaks) >0){
for (i in 1:nrow(peaks)){
#for (i in 1:1){
#Plot 1
#marker = find_marker(gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i])
#gp <- g[,marker]
#gp[gp==1] <- "AA"
#gp[gp==2] <- "AB"
#gp[gp==0] <- NA
#plot_pxg(gp, gm$covar[,peaks$phenotype[i]], ylab=peaks$phenotype[i], sort=FALSE)
#title(main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i]," )"), line=0.2)
###dev.off()
g <- maxmarg(pr.qc, gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i], return_char=TRUE)
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/","qtl_effect_", i, ".png"))
#par(mar=c(4.1, 4.1, 1.5, 0.6))
plot_pxg(g, gm$covar[,peaks$phenotype[i]], ylab=peaks$phenotype[i], sort=FALSE)
title(main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i]," )"), line=0.2)
##dev.off()
chr = peaks$chr[i]
# Plot 2
pr_sub <- pull_genoprobint(pr.qc, gm$gmap, chr, c(peaks$ci_lo[i], peaks$ci_hi[i]))
#coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar)
#coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], Xcovar=Xcovar)
#coeff <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
#coeff_sub <- scan1coef(pr_sub[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
blup <- scan1blup(pr.qc[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)
blup_sub <- scan1blup(pr_sub[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)
write.csv(as.data.frame(blup_sub), paste0("data/ici.vs.pbs_blup_sub_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr4.csv"), quote=F)
#plot_coef(coeff,
# gm$gmap, columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i]," [scan1coeff; positions in cM])")
# )
#plot_coef(coeff_sub,
# gm$gmap, columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i],"; 1.5 LOD drop interval [scan1coeff; positions in cM] ) ")
# )
plot_coef(blup,
gm$gmap, columns=1:2,
bgcolor="gray95", legend="bottomleft",
main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i]," [scan1blup; positions in cM])")
)
plot_coef(blup_sub,
gm$gmap, columns=1:2,
bgcolor="gray95", legend="bottomleft",
main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i],"; 1.5 LOD drop interval [scan1blup; positions in cM])")
)
# Plot 3
#c2effB <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary", contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
#c2effBb <- scan1blup(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]],Xcovar=Xcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
#plot(c2effB, gm$gmap[chr], columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
# )
#plot(c2effBb, gm$gmap[chr], columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
# )
##last_coef <- unclass(c2effB)[nrow(c2effB),2:3] # last two coefficients
##for(t in seq(along=last_coef))
## axis(side=4, at=last_coef[t], names(last_coef)[t], tick=FALSE)
#Table 1
chr = peaks_mba$chr[i]
start=as.numeric(peaks_mba$ci_lo[i])
end=as.numeric(peaks_mba$ci_hi[i])
genesgss = query_genes(chr, start, end)
write.csv(genesgss, file=paste0("data/ici.vs.pbs_genes_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr4.csv"), quote=F)
rownames(genesgss) <- NULL
genesgss$strand_old = genesgss$strand
genesgss$strand[genesgss$strand=="+"] <- "positive"
genesgss$strand[genesgss$strand=="-"] <- "negative"
#genesgss <-
#table <-
#genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")] %>%
#kable(escape = F,align = c("ccccccccccc")) %>%
#kable_styling("striped", full_width = T) #%>%
#cat #%>%
#column_spec(1, bold=TRUE)
#
#print(kable(genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")], escape = F,align = c("ccccccccccc")))
print(kable(genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")], "html") %>% kable_styling("striped", full_width = T))
}
} else {
print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}
[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.72035707026121 [autosomes]/2.58944938717251 [x-chromosome]”
gm
Object of class cross2 (crosstype "bc")
Total individuals 138
No. genotyped individuals 138
No. phenotyped individuals 138
No. with both geno & pheno 138
No. phenotypes 1
No. covariates 7
No. phenotype covariates 0
No. chromosomes 20
Total markers 26548
No. markers by chr:
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
2374 2374 1623 1691 1568 1703 1464 1468 1685 974 1671 1134 1377 1411 876 751
17 18 19 X
330 770 920 384
#detach("package:qtl2", unload=TRUE)
#library(qtl)
cross <- qtl::read.cross("csv", file = "data/ici.vs.pbs_gm_qtl_snpsqc_5.batches_mis_conditional_1-peak-chr4.csv",alleles=c("A","B"))
--Read the following data:
138 individuals
26548 markers
4 phenotypes
--Cross type: bc
cross <- qtl::jittermap(cross)
summary(cross)
Backcross
No. individuals: 138
No. phenotypes: 4
Percent phenotyped: 100 100 100 100
No. chromosomes: 20
Autosomes: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
X chr: X
Total markers: 26548
No. markers: 2374 2374 1623 1691 1568 1703 1464 1468 1685 974 1671
1134 1377 1411 876 751 330 770 920 384
Percent genotyped: 99.5
Genotypes (%):
Autosomes: AA:54.4 AB:45.6
X chromosome: AA:53.3 AB:46.7
cross.probs <- qtl::calc.genoprob(cross)
print("method == hk")
[1] "method == hk"
add.covars = qtl::pull.pheno(cross.probs, c("UNC8250659"))
scanone.hk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="hk", addcovar = add.covars)
operm.hk <- qtl::scanone(cross.probs, method = "hk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE, addcovar = add.covars)
plot(operm.hk)
print(summary(operm.hk, alpha=c(0.01, 0.05, 0.1)))
Autosome LOD thresholds (10 permutations)
lod
1% 2.62
5% 2.46
10% 2.26
X chromosome LOD thresholds (186 permutations)
lod
1% 2.52
5% 2.41
10% 2.26
#plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")
#qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.1, col = 'purple')
ymx <- maxlod(out) # overall maximum LOD score
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]"))
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.1, col = 'purple')
ymx <- 11
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]\n(using same scale as eoi vs ici for easier comparison)"))
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.1, col = 'purple')
print(as.data.frame(summary(scanone.hk, perms=operm.hk, pvalues=TRUE, format="allpeaks")))
chr pos lod pval
UNC163443 1 4.774075 1.3742470 0.9116914
UNC2987704 2 27.689343 0.8724495 1.0000000
JAX00521745 3 20.613263 0.7585338 1.0000000
JAX00556948 4 41.038578 0.7729973 1.0000000
JAX00585101 5 36.216736 0.8544324 1.0000000
UNC10923091 6 18.321248 0.7018820 1.0000000
JAX00657315 7 81.940339 0.7731087 1.0000000
UNCHS023364 8 35.540812 1.5630473 0.7188828
UNCHS026281 9 40.415965 0.5497421 1.0000000
UNCHS028001 10 21.783253 1.0219015 1.0000000
UNCHS030712 11 32.135777 0.8396617 1.0000000
UNC21787084 12 53.288083 0.7631460 1.0000000
UNC22384241 13 13.831342 1.6038654 0.7188828
UNCHS038350 14 30.005599 0.4749227 1.0000000
UNC25285746 15 12.031111 0.8983676 1.0000000
UNC26465114 16 13.431084 0.7730271 1.0000000
JAX00077123 17 31.150016 0.7729946 1.0000000
UNC29709766 18 55.191705 0.5543284 1.0000000
UNC29893228 19 8.029054 1.6298590 0.7188828
JAX00176908 X 4.172023 0.7731463 0.9999829
print("all peaks with a p-value less or equal to 0.05 (suggestive)")
[1] "all peaks with a p-value less or equal to 0.05 (suggestive)"
print(as.data.frame(summary(scanone.hk, perms=operm.hk, alpha=0.05, pvalues=TRUE, format="allpeaks")))
[1] chr pos lod
<0 rows> (or 0-length row.names)
#print("method == ehk")
#scanone.ehk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="ehk")
#operm.ehk <- qtl::scanone(cross.probs, method = "ehk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE)
#plot(operm.ehk)
#print(summary(operm.ehk, alpha=c(0.01, 0.05, 0.1)))
#plot(scanone.ehk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")
#qtl::add.threshold(scanone.ehk, perms= operm.ehk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.ehk, perms= operm.ehk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.ehk, perms= operm.ehk, alpha=0.1, col = 'purple')
#print(as.data.frame(summary(scanone.ehk)))
#print(as.data.frame(summary(scanone.ehk, perms=operm.ehk, alpha=0.05, pvalues=TRUE, format="allpeaks")))
#gm
Xcovar <- get_x_covar(gm)
#addcovar = model.matrix(~Sex, data = covars)[,-1]
addcovar = model.matrix(~UNC18240977, data = covars)[,-1]
#K <- calc_kinship(pr.qc, type = "loco")
#heatmap(K[[1]])
#K.overall <- calc_kinship(pr.qc, type = "overall")
#heatmap(K.overall)
kinship <- calc_kinship(pr.qc)
heatmap(kinship)
#operm <- scan1perm(pr.qc, gm$covar$phenos, Xcovar=Xcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, addcovar = addcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, n_perm=2000)
operm <- scan1perm(pr.qc, gm$covar["ICI.vs.PBS"], model="binary", n_perm=10, perm_Xsp=TRUE, chr_lengths=chr_lengths(gm$gmap), addcovar = addcovar)
summary_table<-data.frame(unclass(summary(operm, alpha=c(0.01, 0.05, 0.1))))
names(summary_table) <- c("autosomes","X")
summary_table$significance.level <- rownames(summary_table)
rownames(summary_table) <- NULL
summary_table[c(3,1:2)] %>%
kable(escape = F,align = c("ccc")) %>%
kable_styling("striped", full_width = T) %>%
column_spec(1, bold=TRUE)
significance.level | autosomes | X |
---|---|---|
0.01 | 3.179263 | 3.082049 |
0.05 | 3.107175 | 3.001548 |
0.1 | 3.016845 | 2.896273 |
The figures below show QTL maps for each phenotype
out <- scan1(pr.qc, gm$covar["ICI.vs.PBS"], Xcovar=Xcovar, model="binary", addcovar = addcovar)
summary_table<-data.frame(unclass(summary(operm, alpha=c(0.01, 0.05, 0.1))))
plot_lod<-function(out,map){
for (i in 1:dim(out)[2]){
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i], "_lod.png"))
ymx <- maxlod(out) # overall maximum LOD score
plot(out, map, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " [positions in cM]"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#par(mar=c(5.1, 6.1, 1.1, 1.1))
ymx <- 11 # overall maximum LOD score
plot(out, map, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " [positions in cM] \n(using same scale as eoi vs ici for easier comparison)"))
add_threshold(map, summary(operm, alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#for (j in 1: dim(summary_table)[1]){
# abline(h=summary_table[j, i],col="red")
# text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
#}
#dev.off()
}
}
plot_lod(out,gm$gmap)
The table below shows QTL peaks associated with the phenotype. We use the 95% threshold from the permutations to find peaks.
peaks <- find_peaks(out, gm$gmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, peakdrop=3, drop=1.5)
if(nrow(peaks) >0){
peaks$marker <- find_marker(gm$gmap, chr=peaks$chr,pos=peaks$pos)
names(peaks)[2] <- c("phenotype")
peaks <- peaks[-1]
rownames(peaks) <- NULL
#print(kable(peaks, "html")
# %>% kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
# )
print(kable(peaks, escape = F, align = c("cccccccc"), "html")
%>% kable_styling("striped", full_width = T)%>%
column_spec(1, bold=TRUE)
)
#peaks[] %>%
# kable(escape = F,align = c("cccccccc")) %>%
# kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
#plot only peak chromosomes
plot_lod_chr<-function(out,map,chrom){
for (i in 1:dim(out)[2]){
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i], "_lod.png"))
#par(mar=c(5.1, 6.1, 1.1, 1.1))
ymx <- maxlod(out) # overall maximum LOD score
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in cM]"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#for (j in 1: dim(summary_table)[1]){
# abline(h=summary_table[j, i],col="red")
# text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
#}
#dev.off()
ymx <- 11
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in cM]\n(using same scale as eoi vs. ici for easier comparison)"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
}
}
for(i in unique(peaks$chr)){
#for (i in 1:nrow(peaks)){
#plot_lod_chr(out,gm$gmap, peaks$chr[i])
plot_lod_chr(out,gm$gmap, i)
}
} else {
print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}
[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 3.10717507101817 [autosomes]/3.00154804082885 [x-chromosome]”
print("peaks in MB positions")
[1] “peaks in MB positions”
peaks_mba <- find_peaks(out, gm$pmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, peakdrop=3, drop=1.5)
if(nrow(peaks) >0){
peaks_mba$marker <- find_marker(gm$pmap, chr=peaks_mba$chr,pos=peaks_mba$pos)
names(peaks_mba)[2] <- c("phenotype")
peaks_mba <- peaks_mba[-1]
#peaks_mbl <- list()
##corresponding info in Mb
#for(i in 1:nrow(peaks)){
# #lodindex <- peaks$lodindex[i]
# phenotype <- peaks$phenotype[i]
# chr <- as.character(peaks$chr[i])
# lod <- peaks$lod[i]
# mark <- peaks$marker[i]
# pos <- mapdf[mapdf$marker==mark,]$pmapdf
# ci_lo <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_lo[i] & mapdfnd$chr == peaks$chr[i])]
# ci_hi <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_hi[i] & mapdfnd$chr == peaks$chr[i])]
# peaks_mb=as.data.frame(cbind(phenotype, chr, pos, lod, ci_lo, ci_hi, mark))
# names(peaks_mb)[7] <- c("marker")
# peaks_mbl[[i]] <- peaks_mb
#}
#peaks_mba2 <- do.call(rbind, peaks_mbl)
#peaks_mba2 <- as.data.frame(peaks_mba)
#peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")] <- sapply(peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")], as.numeric)
rownames(peaks_mba) <- NULL
#print(kable(peaks_mba, "html")
# %>% kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
# )
print(kable(peaks_mba, escape = F, align = c("cccccccc"), "html")
%>% kable_styling("striped", full_width = T)%>%
column_spec(1, bold=TRUE)
)
#peaks_mba[] %>%
# kable(escape = F,align = c("cccccccc")) %>%
# kable_styling("striped", full_width = T) %>%
# column_spec(1, bold=TRUE)
plot_lod_chr_mb<-function(out,map,chrom){
for (i in 1:dim(out)[2]){
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i], "_lod.png"))
#par(mar=c(5.1, 6.1, 1.1, 1.1))
ymx <- maxlod(out) # overall maximum LOD score
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in MB]"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
#for (j in 1: dim(summary_table)[1]){
# abline(h=summary_table[j, i],col="red")
# text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
#}
#dev.off()
ymx <- 11
plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
#legend("topright", lwd=2, colnames(out)[i], bg="gray90")
title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in MB]\n(using same scale as eoi vs. ici for easier comparison)"))
add_threshold(map, summary(operm,alpha=0.1), col = 'purple')
add_threshold(map, summary(operm, alpha=0.05), col = 'red')
add_threshold(map, summary(operm, alpha=0.01), col = 'blue')
}
}
for(i in unique(peaks_mba$chr)){
#for (i in 1:nrow(peaks_mba)){
#plot_lod_chr_mb(out,gm$pmap, peaks_mba$chr[i])
plot_lod_chr_mb(out,gm$pmap,i)
}
} else {
print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}
[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 3.10717507101817 [autosomes]/3.00154804082885 [x-chromosome]”
For each peak LOD location we give a list of gene
query_variants <- create_variant_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/cc_variants.sqlite")
query_genes <- create_gene_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/mouse_genes_mgi.sqlite")
if(nrow(peaks) >0){
for (i in 1:nrow(peaks)){
#for (i in 1:1){
#Plot 1
#marker = find_marker(gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i])
#gp <- g[,marker]
#gp[gp==1] <- "AA"
#gp[gp==2] <- "AB"
#gp[gp==0] <- NA
#plot_pxg(gp, gm$covar[,peaks$phenotype[i]], ylab=peaks$phenotype[i], sort=FALSE)
#title(main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i]," )"), line=0.2)
###dev.off()
g <- maxmarg(pr.qc, gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i], return_char=TRUE)
#png(filename=paste0("/Users/chenm/Documents/qtl/Jai/","qtl_effect_", i, ".png"))
#par(mar=c(4.1, 4.1, 1.5, 0.6))
plot_pxg(g, gm$covar[,peaks$phenotype[i]], ylab=peaks$phenotype[i], sort=FALSE)
title(main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i]," )"), line=0.2)
##dev.off()
chr = peaks$chr[i]
# Plot 2
pr_sub <- pull_genoprobint(pr.qc, gm$gmap, chr, c(peaks$ci_lo[i], peaks$ci_hi[i]))
#coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar)
#coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], Xcovar=Xcovar)
#coeff <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
#coeff_sub <- scan1coef(pr_sub[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
blup <- scan1blup(pr.qc[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)
blup_sub <- scan1blup(pr_sub[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)
write.csv(as.data.frame(blup_sub), paste0("data/ici.vs.pbs_blup_sub_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr10.csv"), quote=F)
#plot_coef(coeff,
# gm$gmap, columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i]," [scan1coeff; positions in cM])")
# )
#plot_coef(coeff_sub,
# gm$gmap, columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i],"; 1.5 LOD drop interval [scan1coeff; positions in cM] ) ")
# )
plot_coef(blup,
gm$gmap, columns=1:2,
bgcolor="gray95", legend="bottomleft",
main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i]," [scan1blup; positions in cM])")
)
plot_coef(blup_sub,
gm$gmap, columns=1:2,
bgcolor="gray95", legend="bottomleft",
main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i],"; 1.5 LOD drop interval [scan1blup; positions in cM])")
)
# Plot 3
#c2effB <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary", contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
#c2effBb <- scan1blup(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]],Xcovar=Xcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
#plot(c2effB, gm$gmap[chr], columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
# )
#plot(c2effBb, gm$gmap[chr], columns=1:2,
# bgcolor="gray95", legend="bottomleft",
# main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
# )
##last_coef <- unclass(c2effB)[nrow(c2effB),2:3] # last two coefficients
##for(t in seq(along=last_coef))
## axis(side=4, at=last_coef[t], names(last_coef)[t], tick=FALSE)
#Table 1
chr = peaks_mba$chr[i]
start=as.numeric(peaks_mba$ci_lo[i])
end=as.numeric(peaks_mba$ci_hi[i])
genesgss = query_genes(chr, start, end)
write.csv(genesgss, file=paste0("data/ici.vs.pbs_genes_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr10.csv"), quote=F)
rownames(genesgss) <- NULL
genesgss$strand_old = genesgss$strand
genesgss$strand[genesgss$strand=="+"] <- "positive"
genesgss$strand[genesgss$strand=="-"] <- "negative"
#genesgss <-
#table <-
#genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")] %>%
#kable(escape = F,align = c("ccccccccccc")) %>%
#kable_styling("striped", full_width = T) #%>%
#cat #%>%
#column_spec(1, bold=TRUE)
#
#print(kable(genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")], escape = F,align = c("ccccccccccc")))
print(kable(genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")], "html") %>% kable_styling("striped", full_width = T))
}
} else {
print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}
[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 3.10717507101817 [autosomes]/3.00154804082885 [x-chromosome]”
gm
Object of class cross2 (crosstype "bc")
Total individuals 138
No. genotyped individuals 138
No. phenotyped individuals 138
No. with both geno & pheno 138
No. phenotypes 1
No. covariates 7
No. phenotype covariates 0
No. chromosomes 20
Total markers 26548
No. markers by chr:
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
2374 2374 1623 1691 1568 1703 1464 1468 1685 974 1671 1134 1377 1411 876 751
17 18 19 X
330 770 920 384
#detach("package:qtl2", unload=TRUE)
#library(qtl)
cross <- qtl::read.cross("csv", file = "data/ici.vs.pbs_gm_qtl_snpsqc_5.batches_mis_conditional_1-peak-chr10.csv",alleles=c("A","B"))
--Read the following data:
138 individuals
26548 markers
4 phenotypes
--Cross type: bc
cross <- qtl::jittermap(cross)
summary(cross)
Backcross
No. individuals: 138
No. phenotypes: 4
Percent phenotyped: 100 100 100 100
No. chromosomes: 20
Autosomes: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
X chr: X
Total markers: 26548
No. markers: 2374 2374 1623 1691 1568 1703 1464 1468 1685 974 1671
1134 1377 1411 876 751 330 770 920 384
Percent genotyped: 99.5
Genotypes (%):
Autosomes: AA:54.4 AB:45.6
X chromosome: AA:53.3 AB:46.7
cross.probs <- qtl::calc.genoprob(cross)
print("method == hk")
[1] "method == hk"
add.covars = qtl::pull.pheno(cross.probs, c("UNC18240977"))
scanone.hk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="hk", addcovar = add.covars)
operm.hk <- qtl::scanone(cross.probs, method = "hk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE, addcovar = add.covars)
plot(operm.hk)
print(summary(operm.hk, alpha=c(0.01, 0.05, 0.1)))
Autosome LOD thresholds (10 permutations)
lod
1% 2.71
5% 2.63
10% 2.53
X chromosome LOD thresholds (186 permutations)
lod
1% 2.79
5% 2.67
10% 2.52
#plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")
#qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.1, col = 'purple')
ymx <- maxlod(out) # overall maximum LOD score
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]"))
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.1, col = 'purple')
ymx <- 11
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]\n(using same scale as eoi vs ici for easier comparison)"))
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk, perms= operm.hk, alpha=0.1, col = 'purple')
print(as.data.frame(summary(scanone.hk, perms=operm.hk, pvalues=TRUE, format="allpeaks")))
chr pos lod pval
UNC163443 1 4.774075 1.3742470 1.0000000
UNC2987704 2 27.689343 0.8724495 1.0000000
JAX00521745 3 20.613263 0.7585338 1.0000000
JAX00556948 4 41.038578 0.7729973 1.0000000
JAX00585101 5 36.216736 0.8544324 1.0000000
UNC10923091 6 18.321248 0.7018820 1.0000000
JAX00657315 7 81.940339 0.7731087 1.0000000
UNCHS023364 8 35.540812 1.5630473 0.8166471
UNCHS026281 9 40.415965 0.5497421 1.0000000
UNCHS028001 10 21.783253 1.0219015 1.0000000
UNCHS030712 11 32.135777 0.8396617 1.0000000
UNC21787084 12 53.288083 0.7631460 1.0000000
UNC22384241 13 13.831342 1.6038654 0.8166471
UNCHS038350 14 30.005599 0.4749227 1.0000000
UNC25285746 15 12.031111 0.8983676 1.0000000
UNC26465114 16 13.431084 0.7730271 1.0000000
JAX00077123 17 31.150016 0.7729946 1.0000000
UNC29709766 18 55.191705 0.5543284 1.0000000
UNC29893228 19 8.029054 1.6298590 0.8166471
JAX00176908 X 4.172023 0.7731463 0.9999829
print("all peaks with a p-value less or equal to 0.05 (suggestive)")
[1] "all peaks with a p-value less or equal to 0.05 (suggestive)"
print(as.data.frame(summary(scanone.hk, perms=operm.hk, alpha=0.05, pvalues=TRUE, format="allpeaks")))
[1] chr pos lod
<0 rows> (or 0-length row.names)
#print("method == ehk")
#scanone.ehk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="ehk")
#operm.ehk <- qtl::scanone(cross.probs, method = "ehk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE)
#plot(operm.ehk)
#print(summary(operm.ehk, alpha=c(0.01, 0.05, 0.1)))
#plot(scanone.ehk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")
#qtl::add.threshold(scanone.ehk, perms= operm.ehk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.ehk, perms= operm.ehk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.ehk, perms= operm.ehk, alpha=0.1, col = 'purple')
#print(as.data.frame(summary(scanone.ehk)))
#print(as.data.frame(summary(scanone.ehk, perms=operm.ehk, alpha=0.05, pvalues=TRUE, format="allpeaks")))
R version 3.5.1 (2018-07-02)
Platform: x86_64-apple-darwin15.6.0 (64-bit)
Running under: macOS 10.15.7
Matrix products: default
BLAS: /Library/Frameworks/R.framework/Versions/3.5/Resources/lib/libRblas.0.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/3.5/Resources/lib/libRlapack.dylib
locale:
[1] en_AU.UTF-8/en_AU.UTF-8/en_AU.UTF-8/C/en_AU.UTF-8/en_AU.UTF-8
attached base packages:
[1] stats graphics grDevices utils datasets methods base
other attached packages:
[1] abind_1.4-5 qtl2_0.22 reshape2_1.4.3 ggplot2_3.3.6
[5] tibble_3.1.7 psych_2.2.5 readxl_1.4.0 cluster_2.0.7-1
[9] dplyr_1.0.9 optparse_1.6.6 rhdf5_2.26.2 mclust_5.4.5
[13] tidyr_1.2.0 data.table_1.14.2 knitr_1.29 kableExtra_1.3.4
[17] workflowr_1.6.2
loaded via a namespace (and not attached):
[1] httr_1.4.3 bit64_0.9-7 viridisLite_0.3.0 assertthat_0.2.1
[5] highr_0.8 blob_1.2.1 cellranger_1.1.0 yaml_2.2.1
[9] gdtools_0.2.1 pillar_1.7.0 RSQLite_2.2.0 backports_1.1.5
[13] lattice_0.20-35 glue_1.6.2 digest_0.6.25 promises_1.1.0
[17] rvest_1.0.2 colorspace_1.4-1 htmltools_0.5.2 httpuv_1.5.2
[21] plyr_1.8.6 pkgconfig_2.0.3 purrr_0.3.4 scales_1.1.1
[25] webshot_0.5.3 svglite_1.2.3 qtl_1.46-2 getopt_1.20.3
[29] later_1.0.0 git2r_0.26.1 generics_0.0.2 ellipsis_0.3.2
[33] withr_2.5.0 cli_3.3.0 mnormt_1.5-6 magrittr_2.0.3
[37] crayon_1.5.1 memoise_1.1.0 evaluate_0.14 fs_1.3.2
[41] fansi_0.4.1 nlme_3.1-137 xml2_1.3.2 tools_3.5.1
[45] lifecycle_1.0.1 stringr_1.4.0 Rhdf5lib_1.4.3 munsell_0.5.0
[49] compiler_3.5.1 systemfonts_0.1.1 rlang_1.0.3 grid_3.5.1
[53] rstudioapi_0.13 rmarkdown_2.3 gtable_0.3.0 DBI_1.1.0
[57] R6_2.4.1 fastmap_1.1.0 bit_1.1-15.2 utf8_1.1.4
[61] rprojroot_1.3-2 stringi_1.4.6 parallel_3.5.1 Rcpp_1.0.4.6
[65] vctrs_0.4.1 tidyselect_1.1.2 xfun_0.15