all OR calcs using sapply and output as df

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Tanushree Tunstall 2020-06-22 18:17:06 +01:00
parent 8f272bdc17
commit 18998092f4

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@ -1,5 +1,5 @@
#########################################################
# TASK: To compare OR from master data
# TASK: To compare OR from master snps
# chisq, fisher test and logistic and adjusted logistic
#########################################################
getwd()
@ -28,10 +28,10 @@ outdir = paste0(datadir, '/', drug, '/', 'output')
in_filename = 'original_tanushree_data_v2.csv'
#in_filename = 'mtb_gwas_v3.csv'
infile = paste0(datadir, '/', in_filename)
cat(paste0('Reading infile1: raw data', ' ', infile) )
cat(paste0('Reading infile1: raw snps', ' ', infile) )
# infile2: _gene associated meta data file to extract valid snps and add calcs to.
# This is outfile3 from data_extraction.py
# infile2: _gene associated meta snps file to extract valid snps and add calcs to.
# This is outfile3 from snps_extraction.py
in_filename_metadata = paste0(tolower(gene), '_metadata.csv')
infile_metadata = paste0(outdir, '/', in_filename_metadata)
cat(paste0('Reading infile2: gene associated metadata:', infile_metadata))
@ -39,17 +39,17 @@ cat(paste0('Reading infile2: gene associated metadata:', infile_metadata))
#===========
# output
#===========
out_filename = paste0(tolower(gene),'_', 'meta_data_with_AF_OR.csv')
out_filename = paste0(tolower(gene),'_', 'af_or.csv')
outfile = paste0(outdir, '/', out_filename)
cat(paste0('Output file with full path:', outfile))
#%% end of variable assignment for input and output files
#########################################################
# 1: Read master/raw data stored in Data/
# 1: Read master/raw snps stored in snps/
#####################################################
#===============
# Step 1: read raw data (all remove entries with NA in pza column)
# Step 1: read raw snps (all remove entries with NA in pza column)
#===============
raw_data_all = read.csv(infile, stringsAsFactors = F)
@ -147,7 +147,6 @@ if(nrow(gene_snps_or) == expected_rows){
gene_snps_unique = unique(gene_snps_or$mutation)
cat(paste0('Total no. of distinct comp snps to perform OR calcs: ', length(gene_snps_unique)))
#=====================================
#OR calcs using the following 4
#1) chisq.test
@ -163,7 +162,7 @@ cat(paste0('Total no. of distinct comp snps to perform OR calcs: ', length(gene_
# Define OR function
#x = as.numeric(mut)
#y = dst
logistic_chisq_or = function(x,y){
custom_chisq_or = function(x,y){
tab = as.matrix(table(x,y))
a = tab[2,2]
if (a==0){ a<-0.5}
@ -179,7 +178,7 @@ logistic_chisq_or = function(x,y){
#========================
# TEST WITH ONE
#========================
i = "pnca_p.trp68gly"
i = "pnca_p.gln10pro"
i = "pnca_p.leu159arg"
@ -211,6 +210,11 @@ table(mut, dst, sid)
#============================
# compare OR
chisq.test(table(mut,dst))
chisq.test(table(mut,dst)) $ statistic
f = chisq.test(table(mut,dst)) $ statistic
chisq.test(dst, mut) $ statistic
fisher.test(table(mut, dst))
fisher.test(table(mut, dst))$p.value
fisher.test(table(mut, dst))$estimate
@ -219,53 +223,79 @@ logistic_chisq_or(mut,dst)
# logistic or
summary(model<-glm(dst ~ mut, family = binomial))
or_logistic = exp(summary(model)$coefficients[2,1]); print(or_logistic)
pval_logistic = summary(model)$coefficients[2,4]; print(pval_logistic)
pval_logistic_maxit = summary(model)$coefficients[2,4]; print(pval_logistic_maxit)
# adjusted logistic or
# extract SE of the logistic model for a given snp
logistic_se = summary(model)$coefficients[2,2]
print(paste0('SE:', logistic_se))
# extract Z of the logistic model for a given snp
logistic_zval = summary(model)$coefficients[2,3]
print(paste0('Z-value:', logistic_zval))
# extract confint interval of snp (2 steps, since the output is a named number)
ci_mod = exp(confint(model))[2,]
print(paste0('CI:', ci_mod))
#logistic_ci = paste(ci_mod[["2.5 %"]], ",", ci_mod[["97.5 %"]])
logistic_ci_lower = ci_mod[["2.5 %"]]
logistic_ci_upper = ci_mod[["97.5 %"]]
print(paste0('CI_lower:', logistic_ci_lower))
print(paste0('CI_upper:', logistic_ci_upper))
# adjusted logistic or: doesn't seem to make a difference
summary(model2<-glm(dst ~ mut + sid, family = binomial))
or_logistic2 = exp(summary(model2)$coefficients[2,1]); print(or_logistic2)
pval_logistic2 = summary(model2)$coefficients[2,4]; print(pval_logistic2)
#=========================
#============ looping with sapply
#####################
# iterate: subset
#####################
ors = sapply(gene_snps_unique,function(m){
snps_test = c("pnca_p.trp68gly", "pnca_p.leu4ser", "pnca_p.leu159arg","pnca_p.his57arg" )
snps = snps_test[1:4]
snps
ors = sapply(snps,function(m){
mut = grepl(m,raw_data$all_muts_gene)
logistic_chisq_or(mut,dst)
})
ors
pvals = sapply(gene_snps_unique,function(m){
pvals = sapply(snps,function(m){
mut = grepl(m,raw_data$all_muts_gene)
fisher.test(mut,dst)$p.value
})
pvals
afs = sapply(gene_snps_unique,function(m){
afs = sapply(snps,function(m){
mut = grepl(m,raw_data$all_muts_gene)
mean(mut)
})
afs
# logistic or
ors_logistic = sapply(gene_snps_unique,function(m){
## logistic or
ors_logistic = sapply(snps,function(m){
mut = grepl(m,raw_data$all_muts_gene)
model<-glm(dst ~ mut, family = binomial)
or_logistic = exp(summary(model)$coefficients[2,1])
#pval_logistic = summary(model)$coefficients[2,4]
#logistic_se = summary(model)$coefficients[2,2]
#logistic_zval = summary(model)$coefficients[2,3]
#ci_mod = exp(confint(model))[2,]
#logistic_ci_lower = ci_mod[["2.5 %"]]
#logistic_ci_upper = ci_mod[["97.5 %"]]
})
ors_logistic
head(ors_logistic); head(names(ors_logistic))
## logistic p-value
pvals_logistic = sapply(gene_snps_unique,function(m){
pvals_logistic = sapply(snps,function(m){
mut = grepl(m,raw_data$all_muts_gene)
model<-glm(dst ~ mut , family = binomial)
pval_logistic = summary(model)$coefficients[2,4]
@ -274,7 +304,7 @@ pvals_logistic = sapply(gene_snps_unique,function(m){
head(pvals_logistic); head(names(pvals_logistic))
## logistic se
se_logistic = sapply(gene_snps_unique,function(m){
se_logistic = sapply(snps,function(m){
mut = grepl(m,raw_data$all_muts_gene)
model<-glm(dst ~ mut , family = binomial)
logistic_se = summary(model)$coefficients[2,2]
@ -293,7 +323,7 @@ zval_logistic = sapply(gene_snps_unique,function(m){
head(zval_logistic); head(names(zval_logistic))
## logistic ci - lower bound
ci_lb_logistic = sapply(gene_snps_unique,function(m){
ci_lb_logistic = sapply(snps,function(m){
mut = grepl(m,raw_data$all_muts_gene)
model<-glm(dst ~ mut , family = binomial)
ci_mod = exp(confint(model))[2,]
@ -303,7 +333,7 @@ ci_lb_logistic = sapply(gene_snps_unique,function(m){
head(ci_lb_logistic); head(names(ci_lb_logistic))
## logistic ci - upper bound
ci_ub_logistic = sapply(gene_snps_unique,function(m){
ci_ub_logistic = sapply(snps,function(m){
mut = grepl(m,raw_data$all_muts_gene)
model<-glm(dst ~ mut , family = binomial)
ci_mod = exp(confint(model))[2,]
@ -314,7 +344,7 @@ ci_ub_logistic = sapply(gene_snps_unique,function(m){
head(ci_ub_logistic); head(names(ci_ub_logistic))
# logistic adj # Doesn't seem to make a difference
logistic_ors2 = sapply(gene_snps_unique,function(m){
logistic_ors2 = sapply(snps,function(m){
mut = grepl(m,raw_data$all_muts_gene)
c = raw_data$id[mut]
sid = grepl(paste(c,collapse="|"), raw_data$id)
@ -327,50 +357,106 @@ logistic_ors2
or_logistic2; pval_logistic2
head(logistic_ors)
#====================================
# logistic
summary(model<-glm(dst ~ mut
, family = binomial
#, control = glm.control(maxit = 1)
#, options(warn = 1)
))
or_logistic = exp(summary(model)$coefficients[2,1]); print(or_logistic)
pval_logistic_maxit = summary(model)$coefficients[2,4]; print(pval_logistic_maxit)
#===========================================================
#%%
# sapply with multiple values
# extract SE of the logistic model for a given snp
logistic_se = summary(model)$coefficients[2,2]
print(paste0('SE:', logistic_se))
# extract Z of the logistic model for a given snp
logistic_zval = summary(model)$coefficients[2,3]
print(paste0('Z-value:', logistic_zval))
# extract confint interval of snp (2 steps, since the output is a named number)
ci_mod = exp(confint(model))[2,]
print(paste0('CI:', ci_mod))
#logistic_ci = paste(ci_mod[["2.5 %"]], ",", ci_mod[["97.5 %"]])
logistic_ci_lower = ci_mod[["2.5 %"]]
logistic_ci_upper = ci_mod[["97.5 %"]]
print(paste0('CI_lower:', logistic_ci_lower))
print(paste0('CI_upper:', logistic_ci_upper))
#####################
# iterate: subset
#####################
#https://gist.github.com/primaryobjects/33adabc337edd67b4a8d
snps_test = c("pnca_p.trp68gly", "pnca_p.leu4ser", "pnca_p.leu159arg","pnca_p.his57arg" )
data = snps_test[1:2]
snps = snps_test[1:4]
data
################# start loop
for (i in data){
snps
# DV: pyrazinamide 0 or 1
dst = raw_data[[drug]]
# yayy works!
testdf = data.frame()
x = sapply(snps,function(m){
df = data.frame()
mut = grepl(m,raw_data$all_muts_gene)
model<-glm(dst ~ mut, family = binomial)
# allele frequency
afs = mean(mut)
# logistic model
beta_logistic = summary(model)$coefficients[2,1]
or_logistic = exp(summary(model)$coefficients[2,1])
print(paste0('logistic OR:', or_logistic))
pval_logistic = summary(model)$coefficients[2,4]
print(paste0('logistic pval:', pval_logistic))
se_logistic = summary(model)$coefficients[2,2]
zval_logistic = summary(model)$coefficients[2,3]
ci_mod = exp(confint(model))[2,]
ci_lower_logistic = ci_mod[["2.5 %"]]
ci_upper_logistic = ci_mod[["97.5 %"]]
# custom_chisq and fisher: OR p-value and CI
or_mychisq = custom_chisq_or(dst, mut)
or_fisher = fisher.test(dst, mut)$estimate
or_fisher = or_fisher[[1]]
pval_fisher = fisher.test(dst, mut)$p.value
ci_lower_fisher = fisher.test(dst, mut)$conf.int[1]
ci_upper_fisher = fisher.test(dst, mut)$conf.int[2]
# chi sq estimates
estimate_chisq = chisq.test(dst, mut)$statistic; estimate_chisq
est_chisq = estimate_chisq[[1]]; print(est_chisq)
pval_chisq = chisq.test(dst, mut)$p.value
#build a row to append to df
row = data.frame(mutation = m
, af = afs
, beta_logistic = beta_logistic
, or_logistic = or_logistic
, pval_logistic = pval_logistic
, se_logistic = se_logistic
, zval_logistic = zval_logistic
, ci_low_logistic = ci_lower_logistic
, ci_hi_logistic = ci_upper_logistic
, or_mychisq = or_mychisq
, or_fisher = or_fisher
, pval_fisher = pval_fisher
, ci_low_fisher= ci_lower_fisher
, ci_hi_fisher = ci_upper_fisher
, est_chisq = est_chisq
, pval_chisq = pval_chisq
)
#print(row)
testdf <<- rbind(testdf, row)
})
write.csv(testdf, 'test_ors.csv')
#=================================
####################
# iterate: subset
#####################
print(paste0('subset to iterate over;', snps))
# start loop
perfectSeparation <- function(w) {
if(grepl("fitted probabilities numerically 0 or 1 occurred",
as.character(w))) {ww <<- ww+1}
}
for (i in snps){
print(i)
@ -386,7 +472,6 @@ for (i in data){
# table
print(table(dst, mut))
#=====================
# logistic regression, glm.control(maxit = n)
#https://stats.stackexchange.com/questions/11109/how-to-deal-with-perfect-separation-in-logistic-regression
@ -405,6 +490,7 @@ for (i in data){
ci_mod = exp(confint(model))[2,]
logistic_ci_lower = ci_mod[["2.5 %"]]
logistic_ci_upper = ci_mod[["97.5 %"]]
#=====================
# fishers test
#=====================
@ -431,17 +517,7 @@ for (i in data){
, paste0("OR_fisher:", or_fisher, "--->","P-val_fisher:", pval_fisher )
, paste0("Chi_sq_estimate:", est_chisq, "--->","P-val_chisq:", pval_chisq)))
}
i = "gene_p.leu159arg"
mut<-as.numeric(grepl(i,raw_data$all_muts_pza))
# DV
dst<-as.numeric(raw_data$pyrazinamide)
# tablehttps://mail.google.com/mail/?tab=rm&ogbl
table(dst, mut)
#=====================
#=====================
# fishers test
#=====================
#attributes(fisher.test(table(dst, mut)))
@ -453,5 +529,110 @@ table(dst, mut)
# https://stats.stackexchange.com/questions/259635/what-is-the-difference-using-a-fishers-exact-test-vs-a-logistic-regression-for
exact2x2(table(dst, mut),tsmethod="central")
#=====================================================================
# iterate over a df and then add these values
#
my_data = as.data.frame(gene_snps_unique)
colnames(my_data) = "mutation"
print(colnames(my_data))
perfectSeparation <- function(w) {
if(grepl("fitted probabilities numerically 0 or 1 occurred",
as.character(w))) {ww <<- ww+1}
}
for(i in my_data$mutation) {
print(paste0('snp to iterate over:', i))
}
for(i in my_data$mutation) {
print(paste0('snp to iterate over:', i))
#####
# Run logistic regression
#####
#*************
# start logistic regression model building
# set the IV and DV for the logistic regression model and model
#*************
# IV: corresponds to each unique snp (extracted using grep)
mut = as.numeric(grepl(i,raw_data$dr_muts_pza))
# DV: pyrazinamide 0 or 1
dst = as.numeric(raw_data$pyrazinamide)
tab = table(mut, dst)
print(tab)
# glm model: with and without maxit
model = tryCatch( glm(dst ~ mut
, family = binomial
#, control = glm.control(maxit = 1) # only used when required for one step estimator
), warning = perfectSeparation)
model = glm(dst ~ mut, family = binomial)
print(summary(model))
#**********
# extract relevant model output
#**********
# extract log OR i.e the Beta estimate of the logistic model for a given snp
my_logor = summary(model)$coefficients[2,1]
print(paste0('Beta:', my_logor))
# Dervive OR i.e exp(my_or) from the logistic model for a given snp
#my_or = round(exp(summary(model)$coefficients[2,1]), roundto)
my_or = exp(summary(model)$coefficients[2,1])
print(paste0('OR:', my_or))
# extract SE of the logistic model for a given snp
my_se = summary(model)$coefficients[2,2]
print(paste0('SE:', my_se))
# extract Z of the logistic model for a given snp
my_zval = summary(model)$coefficients[2,3]
print(paste0('Z-value:', my_zval))
# extract P-value of the logistic model for a given snp
my_pval = summary(model)$coefficients[2,4]
print(paste0('P-value:', my_pval))
# extract confint interval of snp (2 steps, since the output is a named number)
ci_mod = exp(confint(model))[2,]
#my_ci = paste(ci_mod[["2.5 %"]], ",", ci_mod[["97.5 %"]])
my_ci_lower = ci_mod[["2.5 %"]]
my_ci_upper = ci_mod[["97.5 %"]]
print(paste0('CI_lower:', my_ci_lower))
print(paste0('CI_upper:', my_ci_upper))
#*************
# Assign the regression output in the to df (meta_pza_pnca_snps_only)
# you can use ('=' or '<-/->')
#*************
#my_data$logistic_logOR[my_data$mutation == i] = my_logor
my_or -> my_data$OR[my_data$mutation == i]
my_pval -> my_data$pvalue[my_data$mutation == i]
my_zval -> my_data$zvalue[my_data$mutation == i]
my_se -> my_data$logistic_se[my_data$mutation == i]
my_ci_lower -> my_data$ci_lower[my_data$mutation == i]
my_ci_upper -> my_data$ci_upper[my_data$mutation == i]
#=#=#=#=#=#=#=#
# COMMENT: This assigns the relevant extracted output
# to the df and fills NA where the mutation (row) doesn't exist
# in my mutation list I am iterating over
#=#=#=#=#=#=#=#
}