Last updated: 2022-02-25

Checks: 5 2

Knit directory: Serreze-T1D_Workflow/

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    Untracked:  analysis/genotype.frequencies_ici.vs.eoi.Rmd
    Untracked:  analysis/genotype.frequencies_ici.vs.pbs.Rmd
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with sample outliers

load("data/gm_allqc_4.batches.RData")

#gm_allqc
gm=gm_allqc
gm
Object of class cross2 (crosstype "bc")

Total individuals               188
No. genotyped individuals       188
No. phenotyped individuals      188
No. with both geno & pheno      188

No. phenotypes                    1
No. covariates                    6
No. phenotype covariates          0

No. chromosomes                  20
Total markers                131578

No. markers by chr:
    1     2     3     4     5     6     7     8     9    10    11    12    13 
 9977 10005  7858  7589  7621  7758  7413  6472  6725  6396  7154  6137  6085 
   14    15    16    17    18    19     X 
 5981  5346  5019  5093  4607  3564  4778 
pr <- readRDS("data/serreze_probs_allqc.rds")
#pr <- readRDS("data/serreze_probs.rds")

geno <- read.csv("/Users/corneb/Documents/MyJax/CS/Projects/Serreze/haplotype.reconstruction/output_hh/sample_geno_bc.csv", as.is=T)
names(geno) <- gsub("\\.","-",names(geno))
rownames(geno) <- geno$marker
## extracting animals with ici and eoi group status
miceinfo <- gm$covar[gm$covar$group == "EOI" | gm$covar$group == "ICI",]
table(miceinfo$group)

EOI ICI 
 69  92 
mice.ids <- rownames(miceinfo)

gm <- gm[mice.ids]
gm
Object of class cross2 (crosstype "bc")

Total individuals               161
No. genotyped individuals       161
No. phenotyped individuals      161
No. with both geno & pheno      161

No. phenotypes                    1
No. covariates                    6
No. phenotype covariates          0

No. chromosomes                  20
Total markers                131578

No. markers by chr:
    1     2     3     4     5     6     7     8     9    10    11    12    13 
 9977 10005  7858  7589  7621  7758  7413  6472  6725  6396  7154  6137  6085 
   14    15    16    17    18    19     X 
 5981  5346  5019  5093  4607  3564  4778 
table(gm$covar$group)

EOI ICI 
 69  92 
covars <- read_csv("data/covar_corrected_ici.vs.eoi.csv")
# removing any missing info
#covars <- subset(covars, covars$age.of.onset!='')
nrow(covars)
[1] 161
table(covars$group)

EOI ICI 
 69  92 
# keeping only informative mice
gm <- gm[covars$Mouse.ID]
gm
Object of class cross2 (crosstype "bc")

Total individuals               161
No. genotyped individuals       161
No. phenotyped individuals      161
No. with both geno & pheno      161

No. phenotypes                    1
No. covariates                    6
No. phenotype covariates          0

No. chromosomes                  20
Total markers                131578

No. markers by chr:
    1     2     3     4     5     6     7     8     9    10    11    12    13 
 9977 10005  7858  7589  7621  7758  7413  6472  6725  6396  7154  6137  6085 
   14    15    16    17    18    19     X 
 5981  5346  5019  5093  4607  3564  4778 
table(gm$covar$group)

EOI ICI 
 69  92 
pr.qc.ids <- pr
for (i in 1:20){pr.qc.ids[[i]] = pr.qc.ids[[i]][covars$Mouse.ID,,]}

geno <- geno[,covars$Mouse.ID]
geno <- geno[marker_names(gm),]
dim(geno)
[1] 131578    161
## calculating genotype frequencies
### from geno genotypes
g <- do.call("cbind", gm$geno)
gf_mar_geno <- t(apply(g, 2, function(a) table(factor(a, 1:2))/sum(a != 0)))
gn_mar_geno <- t(apply(g, 2, function(a) table(factor(a, 0:2))))
#gf_mar_raw<- gf_mar_raw[gf_mar_raw[,2] != "NaN",]
colnames(gf_mar_geno) <- c("freq_AA_geno_table","freq_AB_geno_table")
colnames(gn_mar_geno) <- c("count_missing_geno_table","count_AA_geno_table","count_AB_geno_table")
gfn_mar_geno <- merge(as.data.frame(gn_mar_geno), as.data.frame(gf_mar_geno), by="row.names")
rownames(gfn_mar_geno) <- gfn_mar_geno[,1]
gfn_mar_geno <- gfn_mar_geno[-1]

### from raw using table function in R
#genosl <- list()
#for(i in 1:nrow(geno)){
##for(i in 1:3){
#    genoi <- geno[i,]
#    freqf <- table(factor(geno[i,], c("-","AA","AB")))
#    genoi$count_AA_raw_rowSums <- rowSums(genoi == "AA")
#    genoi$count_AB_raw_rowSums <- rowSums(genoi == "AB")
#    genoi$count_missing_raw_rowSums <- rowSums(genoi == "-")
#    freqf <- t(table(factor(geno[i,], c("-","AA","AB"))))
#    freqf <- as.data.frame(t(freqf[1,]))
#    rownames(freqf) <- rownames(genoi)
#    colnames(freqf) <- c("count_missing_raw_table","count_AA_raw_table","count_AB_raw_table")
#    genoif <- cbind(freqf,genoi[c("count_AA_raw_rowSums","count_AB_raw_rowSums","count_missing_raw_rowSums")])
#    genosl[[i]] = genoif
#}
#gf_mar_raw <- do.call("rbind",genosl)
#gf_mar_raw <- gf_mar_raw[,c(1:3,6,4:5)]
#gf_mar_raw$index <- 1:nrow(gf_mar_raw)

### from probabilities
gf_mar_probs.1 <- calc_geno_freq(pr.qc.ids, by = "marker", omit_x = FALSE)
#gn_mar_probs <- calc_geno_freq(probs, by = "individual", omit_x = FALSE)
gf_mar_probs <- rbind(gf_mar_probs.1$A[,1:2], gf_mar_probs.1$X[,1:2])
colnames(gf_mar_probs) <- paste0("freq_",colnames(gf_mar_probs),"_probs")
gf_mar_probs <- as.data.frame(gf_mar_probs)
gf_mar_probs$index <- 1:nrow(gf_mar_probs)

### merging all genotype frequecies for all markers
#gf_mar.1 <- merge(as.data.frame(gf_mar_raw), as.data.frame(gfn_mar_geno), by="row.names")
#rownames(gf_mar.1) <- gf_mar.1[,1]
#gf_mar.1 <- gf_mar.1[-1]
#gf_mar <- merge(gf_mar.1,as.data.frame(gf_mar_probs), by="row.names")
gf_mar <- merge(as.data.frame(gfn_mar_geno),as.data.frame(gf_mar_probs), by="row.names")
rownames(gf_mar) <- gf_mar[,1]
gf_mar <- gf_mar[-1]
gf_mar <- gf_mar[order(gf_mar$index),]
dim(gf_mar)
[1] 131578      8
# Calculating ratio and flagging informative marker
gf_mar$ratio = as.numeric(gf_mar$freq_AA_geno_table)/as.numeric(gf_mar$freq_AB_geno_table)
gf_mar$Include = ifelse(gf_mar$ratio >= 0.90 & gf_mar$ratio <= 1.10, TRUE,FALSE)
table(gf_mar$Include)

 FALSE   TRUE 
117813  13765 
## filtering out <= 0.05
gf_mar$count.geno <- rowSums(gf_mar[c("freq_AA_geno_table","freq_AB_geno_table")] <=0.05)
filtered_gf_mar_geno <- gf_mar[gf_mar$count.geno != 1,]
filtered_gf_mar_geno <- filtered_gf_mar_geno[,-which(names(filtered_gf_mar_geno) %in% c("count.geno","index"))]
dim(filtered_gf_mar_geno)
[1] 32501     9
table(filtered_gf_mar_geno$Include)

FALSE  TRUE 
18736 13765 
gf_mar$count.probs <- rowSums(gf_mar[c("freq_AA_probs","freq_AB_probs")] <=0.05)
filtered_gf_mar_probs <- gf_mar[gf_mar$count.probs != 1,]
filtered_gf_mar_probs <- filtered_gf_mar_probs[,-which(names(filtered_gf_mar_probs) %in% c("count.geno","count.probs","index"))]
dim(filtered_gf_mar_probs)
[1] 33386     9
table(filtered_gf_mar_probs$Include)

FALSE  TRUE 
22515 10871 
## merging with sample_genos
#filtered_gf_mar_geno_sample <- merge(geno,filtered_gf_mar_geno, by="row.names", all.y=T)
#filtered_gf_mar_geno_sample <- filtered_gf_mar_geno_sample[order(filtered_gf_mar_geno_sample$index),]     
#filtered_gf_mar_geno_sample <- filtered_gf_mar_geno_sample[,-which(names(filtered_gf_mar_geno_sample) %in% c("count.geno","index"))]
#names(filtered_gf_mar_geno_sample)[1] <- c("marker")
#dim(filtered_gf_mar_geno_sample)

#filtered_gf_mar_probs_sample <- merge(geno,filtered_gf_mar_probs, by="row.names", all.y=T)
#filtered_gf_mar_probs_sample <- filtered_gf_mar_probs_sample[order(filtered_gf_mar_probs_sample$index),]
#filtered_gf_mar_probs_sample <- filtered_gf_mar_probs_sample[,-which(names(filtered_gf_mar_probs_sample) %in% c("count.geno","count.probs","index"))]
#names(filtered_gf_mar_probs_sample)[1] <- c("marker")
#dim(filtered_gf_mar_probs_sample)

## saving files
#write.csv(filtered_gf_mar_geno_sample, "data/ici.vs.eoi_sample.genos_marker.freq_low.geno.freq.removed.csv", quote=F)
#write.csv(filtered_gf_mar_probs_sample, "data/ici.vs.eoi_sample.genos_marker.freq_low.probs.freq.removed.csv", quote=F)

write.csv(filtered_gf_mar_geno, "data/ici.vs.eoi_marker.freq_low.geno.freq.removed_geno.ratio.csv", quote=F)
write.csv(filtered_gf_mar_probs, "data/ici.vs.eoi_marker.freq_low.probs.freq.removed_geno.ratio.csv", quote=F)

sample outliers removed

load("data/gm_allqc_4.batches.RData")

#gm_allqc
gm=gm_allqc
gm
Object of class cross2 (crosstype "bc")

Total individuals               188
No. genotyped individuals       188
No. phenotyped individuals      188
No. with both geno & pheno      188

No. phenotypes                    1
No. covariates                    6
No. phenotype covariates          0

No. chromosomes                  20
Total markers                131578

No. markers by chr:
    1     2     3     4     5     6     7     8     9    10    11    12    13 
 9977 10005  7858  7589  7621  7758  7413  6472  6725  6396  7154  6137  6085 
   14    15    16    17    18    19     X 
 5981  5346  5019  5093  4607  3564  4778 
pr <- readRDS("data/serreze_probs_allqc.rds")
#pr <- readRDS("data/serreze_probs.rds")

geno <- read.csv("/Users/corneb/Documents/MyJax/CS/Projects/Serreze/haplotype.reconstruction/output_hh/sample_geno_bc.csv", as.is=T)
names(geno) <- gsub("\\.","-",names(geno))
rownames(geno) <- geno$marker
## extracting animals with ici and eoi group status
miceinfo <- gm$covar[gm$covar$group == "EOI" | gm$covar$group == "ICI",]
table(miceinfo$group)

EOI ICI 
 69  92 
mice.ids <- rownames(miceinfo)

gm <- gm[mice.ids]
gm
Object of class cross2 (crosstype "bc")

Total individuals               161
No. genotyped individuals       161
No. phenotyped individuals      161
No. with both geno & pheno      161

No. phenotypes                    1
No. covariates                    6
No. phenotype covariates          0

No. chromosomes                  20
Total markers                131578

No. markers by chr:
    1     2     3     4     5     6     7     8     9    10    11    12    13 
 9977 10005  7858  7589  7621  7758  7413  6472  6725  6396  7154  6137  6085 
   14    15    16    17    18    19     X 
 5981  5346  5019  5093  4607  3564  4778 
table(gm$covar$group)

EOI ICI 
 69  92 
covars <- read_csv("data/covar_corrected.cleaned_ici.vs.eoi.csv")
# removing any missing info
covars <- subset(covars, covars$age.of.onset!='')
nrow(covars)
[1] 160
table(covars$group)

EOI ICI 
 69  91 
# keeping only informative mice
gm <- gm[covars$Mouse.ID]
gm
Object of class cross2 (crosstype "bc")

Total individuals               160
No. genotyped individuals       160
No. phenotyped individuals      160
No. with both geno & pheno      160

No. phenotypes                    1
No. covariates                    6
No. phenotype covariates          0

No. chromosomes                  20
Total markers                131578

No. markers by chr:
    1     2     3     4     5     6     7     8     9    10    11    12    13 
 9977 10005  7858  7589  7621  7758  7413  6472  6725  6396  7154  6137  6085 
   14    15    16    17    18    19     X 
 5981  5346  5019  5093  4607  3564  4778 
table(gm$covar$group)

EOI ICI 
 69  91 
pr.qc.ids <- pr
for (i in 1:20){pr.qc.ids[[i]] = pr.qc.ids[[i]][covars$Mouse.ID,,]}

geno <- geno[,covars$Mouse.ID]
geno <- geno[marker_names(gm),]
dim(geno)
[1] 131578    160
## calculating genotype frequencies
### from geno genotypes
g <- do.call("cbind", gm$geno)
gf_mar_geno <- t(apply(g, 2, function(a) table(factor(a, 1:2))/sum(a != 0)))
gn_mar_geno <- t(apply(g, 2, function(a) table(factor(a, 0:2))))
#gf_mar_raw<- gf_mar_raw[gf_mar_raw[,2] != "NaN",]
colnames(gf_mar_geno) <- c("freq_AA_geno_table","freq_AB_geno_table")
colnames(gn_mar_geno) <- c("count_missing_geno_table","count_AA_geno_table","count_AB_geno_table")
gfn_mar_geno <- merge(as.data.frame(gn_mar_geno), as.data.frame(gf_mar_geno), by="row.names")
rownames(gfn_mar_geno) <- gfn_mar_geno[,1]
gfn_mar_geno <- gfn_mar_geno[-1]

### from raw using table function in R
#genosl <- list()
#for(i in 1:nrow(geno)){
##for(i in 1:3){
#    genoi <- geno[i,]
#    freqf <- table(factor(geno[i,], c("-","AA","AB")))
#    genoi$count_AA_raw_rowSums <- rowSums(genoi == "AA")
#    genoi$count_AB_raw_rowSums <- rowSums(genoi == "AB")
#    genoi$count_missing_raw_rowSums <- rowSums(genoi == "-")
#    freqf <- t(table(factor(geno[i,], c("-","AA","AB"))))
#    freqf <- as.data.frame(t(freqf[1,]))
#    rownames(freqf) <- rownames(genoi)
#    colnames(freqf) <- c("count_missing_raw_table","count_AA_raw_table","count_AB_raw_table")
#    genoif <- cbind(freqf,genoi[c("count_AA_raw_rowSums","count_AB_raw_rowSums","count_missing_raw_rowSums")])
#    genosl[[i]] = genoif
#}
#gf_mar_raw <- do.call("rbind",genosl)
#gf_mar_raw <- gf_mar_raw[,c(1:3,6,4:5)]
#gf_mar_raw$index <- 1:nrow(gf_mar_raw)

### from probabilities
gf_mar_probs.1 <- calc_geno_freq(pr.qc.ids, by = "marker", omit_x = FALSE)
#gn_mar_probs <- calc_geno_freq(probs, by = "individual", omit_x = FALSE)
gf_mar_probs <- rbind(gf_mar_probs.1$A[,1:2], gf_mar_probs.1$X[,1:2])
colnames(gf_mar_probs) <- paste0("freq_",colnames(gf_mar_probs),"_probs")
gf_mar_probs <- as.data.frame(gf_mar_probs)
gf_mar_probs$index <- 1:nrow(gf_mar_probs)

### merging all genotype frequecies for all markers
#gf_mar.1 <- merge(as.data.frame(gf_mar_raw), as.data.frame(gfn_mar_geno), by="row.names")
#rownames(gf_mar.1) <- gf_mar.1[,1]
#gf_mar.1 <- gf_mar.1[-1]
#gf_mar <- merge(gf_mar.1,as.data.frame(gf_mar_probs), by="row.names")
gf_mar <- merge(as.data.frame(gfn_mar_geno),as.data.frame(gf_mar_probs), by="row.names")
rownames(gf_mar) <- gf_mar[,1]
gf_mar <- gf_mar[-1]
gf_mar <- gf_mar[order(gf_mar$index),]
dim(gf_mar)
[1] 131578      8
# Calculating ratio and flagging informative marker
gf_mar$ratio = as.numeric(gf_mar$freq_AA_geno_table)/as.numeric(gf_mar$freq_AB_geno_table)
gf_mar$Include = ifelse(gf_mar$ratio >= 0.90 & gf_mar$ratio <= 1.10, TRUE,FALSE)
table(gf_mar$Include)

 FALSE   TRUE 
117761  13817 
## filtering out <= 0.05
gf_mar$count.geno <- rowSums(gf_mar[c("freq_AA_geno_table","freq_AB_geno_table")] <=0.05)
filtered_gf_mar_geno <- gf_mar[gf_mar$count.geno != 1,]
filtered_gf_mar_geno <- filtered_gf_mar_geno[,-which(names(filtered_gf_mar_geno) %in% c("count.geno","index"))]
dim(filtered_gf_mar_geno)
[1] 32533     9
table(filtered_gf_mar_geno$Include)

FALSE  TRUE 
18716 13817 
gf_mar$count.probs <- rowSums(gf_mar[c("freq_AA_probs","freq_AB_probs")] <=0.05)
filtered_gf_mar_probs <- gf_mar[gf_mar$count.probs != 1,]
filtered_gf_mar_probs <- filtered_gf_mar_probs[,-which(names(filtered_gf_mar_probs) %in% c("count.geno","count.probs","index"))]
dim(filtered_gf_mar_probs)
[1] 33403     9
table(filtered_gf_mar_probs$Include)

FALSE  TRUE 
22487 10916 
## merging with sample_genos
#filtered_gf_mar_geno_sample <- merge(geno,filtered_gf_mar_geno, by="row.names", all.y=T)
#filtered_gf_mar_geno_sample <- filtered_gf_mar_geno_sample[order(filtered_gf_mar_geno_sample$index),]     
#filtered_gf_mar_geno_sample <- filtered_gf_mar_geno_sample[,-which(names(filtered_gf_mar_geno_sample) %in% c("count.geno","index"))]
#names(filtered_gf_mar_geno_sample)[1] <- c("marker")
#dim(filtered_gf_mar_geno_sample)

#filtered_gf_mar_probs_sample <- merge(geno,filtered_gf_mar_probs, by="row.names", all.y=T)
#filtered_gf_mar_probs_sample <- filtered_gf_mar_probs_sample[order(filtered_gf_mar_probs_sample$index),]
#filtered_gf_mar_probs_sample <- filtered_gf_mar_probs_sample[,-which(names(filtered_gf_mar_probs_sample) %in% c("count.geno","count.probs","index"))]
#names(filtered_gf_mar_probs_sample)[1] <- c("marker")
#dim(filtered_gf_mar_probs_sample)

## saving files
#write.csv(filtered_gf_mar_geno_sample, "data/ici.vs.eoi_sample.genos_marker.freq_low.geno.freq.removed_sample.outliers.removed.csv", quote=F)
#write.csv(filtered_gf_mar_probs_sample, "data/ici.vs.eoi_sample.genos_marker.freq_low.probs.freq.removed_sample.outliers.removed.csv", quote=F)

write.csv(filtered_gf_mar_geno, "data/ici.vs.eoi_marker.freq_low.geno.freq.removed_sample.outliers.removed_geno.ratio.csv", quote=F)
write.csv(filtered_gf_mar_probs, "data/ici.vs.eoi_marker.freq_low.probs.freq.removed_sample.outliers.removed_geno.ratio.csv", quote=F)

R version 3.6.2 (2019-12-12)
Platform: x86_64-apple-darwin15.6.0 (64-bit)
Running under: macOS Catalina 10.15.7

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_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_1.4.4    ggplot2_3.3.5    
 [5] tibble_3.1.2      psych_2.0.7       readxl_1.3.1      cluster_2.1.0    
 [9] dplyr_0.8.5       optparse_1.6.6    rhdf5_2.28.1      mclust_5.4.6     
[13] tidyr_1.0.2       data.table_1.14.0 knitr_1.33        kableExtra_1.1.0 
[17] workflowr_1.6.2  

loaded via a namespace (and not attached):
 [1] httr_1.4.1        bit64_4.0.5       viridisLite_0.4.0 assertthat_0.2.1 
 [5] highr_0.9         blob_1.2.1        cellranger_1.1.0  yaml_2.2.1       
 [9] pillar_1.6.1      RSQLite_2.2.7     backports_1.2.1   lattice_0.20-38  
[13] glue_1.4.2        digest_0.6.27     promises_1.1.0    rvest_0.3.5      
[17] colorspace_2.0-2  htmltools_0.5.1.1 httpuv_1.5.2      plyr_1.8.6       
[21] pkgconfig_2.0.3   purrr_0.3.4       scales_1.1.1      webshot_0.5.2    
[25] getopt_1.20.3     later_1.0.0       git2r_0.26.1      ellipsis_0.3.2   
[29] cachem_1.0.5      withr_2.4.2       mnormt_1.5-7      magrittr_2.0.1   
[33] crayon_1.4.1      memoise_2.0.0     evaluate_0.14     fs_1.4.1         
[37] fansi_0.5.0       nlme_3.1-142      xml2_1.3.1        tools_3.6.2      
[41] hms_0.5.3         lifecycle_1.0.0   stringr_1.4.0     Rhdf5lib_1.6.3   
[45] munsell_0.5.0     compiler_3.6.2    rlang_0.4.11      grid_3.6.2       
[49] rstudioapi_0.13   rmarkdown_2.1     gtable_0.3.0      DBI_1.1.1        
[53] R6_2.5.0          fastmap_1.1.0     bit_4.0.4         utf8_1.2.1       
[57] rprojroot_1.3-2   readr_1.3.1       stringi_1.7.2     parallel_3.6.2   
[61] Rcpp_1.0.7        vctrs_0.3.8       tidyselect_1.0.0  xfun_0.24