LSHTM_analysis/scripts/plotting/structure_figures/replaceBfactor_pdb_stability.R

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R

#!/usr/bin/env Rscript
source("~/git/LSHTM_analysis/config/gid.R")
source("~/git/LSHTM_analysis/scripts/plotting/get_plotting_dfs.R")
#########################################################
# TASK: Replace B-factors in the pdb file with the mean
# normalised stability values.
# read pdb file
# read mcsm mean stability value files
# extract the respective mean values and assign to the
# b-factor column within their respective pdbs
# generate some distribution plots for inspection
#########################################################
# working dir and loading libraries
#source("~/git/LSHTM_analysis/scripts/Header_TT.R")
library(bio3d)
require("getopt", quietly = TRUE) # cmd parse arguments
#========================================================
#========================================================
cat(gene)
gene_match = paste0(gene,"_p."); cat(gene_match)
cat(gene_match)
#=============
# directories
#=============
datadir = paste0("~/git/Data")
indir = paste0(datadir, "/", drug, "/input")
outdir = paste0("~/git/Data", "/", drug, "/output")
#outdir_plots = paste0("~/git/Writing/thesis/images/results/", tolower(gene))
#======
# input
#======
in_filename_pdb = paste0(tolower(gene), "_complex.pdb")
#in_filename_pdb = "~/git/Writing/thesis/images/results/gid/str_figures/gid_complex_copy_arpeg.pdb"
infile_pdb = paste0(indir, "/", in_filename_pdb)
cat(paste0("Input file:", infile_pdb) )
#=======
# output
#=======
outdir_images = paste0("~/git/Writing/thesis/images/results/", tolower(gene), "/")
cat("plots will output to:", outdir_images)
#out_filename_duet_mspdb = paste0(tolower(gene), "_complex_bduet_ms.pdb")
out_filename_duet_mspdb = paste0(tolower(gene), "_complex_b_stab_ms.pdb")
outfile_duet_mspdb = paste0(outdir_images, out_filename_duet_mspdb)
print(paste0("Output file:", outfile_duet_mspdb))
#%%===============================================================
#NOTE: duet here refers to the ensemble stability values
###########################
# Read file: average stability values
# or mcsm_normalised file
###########################
my_df_raw = merged_df3[, c("position", "avg_stability", "avg_stability_scaled")]
# avg by position on the SCALED values
my_df <- my_df_raw %>%
group_by(position) %>%
summarize(avg_stab_sc_pos = mean(avg_stability_scaled))
max(my_df$avg_stab_sc_pos)
min(my_df$avg_stab_sc_pos)
#============================================================
# # scale b/w -1 and 1
# duet_min = min(my_df_by_position['avg_stab_sc_pos'])
# duet_max = max(my_df_by_position['avg_stab_sc_pos'])
#
# # scale the averaged_duet values
# my_df_by_position['avg_stab_sc_pos_scaled'] = lapply(my_df_by_position['avg_stab_sc_pos']
# , function(x) ifelse(x < 0, x/abs(duet_min), x/duet_max))
#
# cat(paste0('Average duet scores:\n', head(my_df_by_position['avg_stab_sc_pos_scaled'])
# , '\n---------------------------------------------------------------'
# , '\nScaled duet scores:\n', head(my_df_by_position['avg_stab_sc_pos_scaled'])))
#
# min(my_df_by_position['avg_stab_sc_pos_scaled'])
# max(my_df_by_position['avg_stab_sc_pos_scaled'])
#============================================================
#############
# Read pdb
#############
# list of 8
my_pdb = read.pdb(infile_pdb
, maxlines = -1
, multi = FALSE
, rm.insert = FALSE
, rm.alt = TRUE
, ATOM.only = FALSE
, hex = FALSE
, verbose = TRUE)
# assign separately for duet and ligand
my_pdb_duet = my_pdb
#=========================================================
# Replacing B factor with mean stability scores
# within the respective dfs
#==========================================================
df_duet= my_pdb_duet[['atom']]
# make a copy: required for downstream sanity checks
d2_duet = df_duet
# sanity checks: B factor
max(df_duet$b); min(df_duet$b)
#==================================================
# histograms and density plots for inspection
# 1: original B-factors
# 2: original mean stability values
# 3: replaced B-factors with mean stability values
#==================================================
# Set the margin on all sides
par(oma = c(3,2,3,0)
, mar = c(1,3,5,2)
#, mfrow = c(3,2)
#, mfrow = c(3,4))
, mfrow = c(3,2))
#=============
# Row 1 plots: original B-factors
# duet and affinity
#=============
hist(df_duet$b
, xlab = ""
, main = "Bfactor stability")
plot(density(df_duet$b)
, xlab = ""
, main = "Bfactor stability")
#=============
# Row 2 plots: original mean stability values
# duet and affinity
#=============
#hist(my_df$averaged_duet
hist(my_df$avg_stab_sc_pos
, xlab = ""
, main = "mean stability values")
#plot(density(my_df$averaged_duet)
plot(density(my_df$avg_stab_sc_pos)
, xlab = ""
, main = "mean stability values")
################################################################
#=========
# step 1_P1
#=========
#df_duet$b = my_df$averaged_duet_scaled[match(df_duet$resno, my_df$position)]
df_duet$b = my_df$avg_stab_sc_pos[match(df_duet$resno, my_df$position)]
#=========
# step 2_P1
#=========
# count NA in Bfactor
b_na_duet = sum(is.na(df_duet$b)) ; b_na_duet
# count number of 0"s in Bactor
sum(df_duet$b == 0)
# replace all NA in b factor with 0
na_rep = 2
df_duet$b[is.na(df_duet$b)] = na_rep
#=========
# step 3_P1
#=========
# sanity check: dim should be same before reassignment
if ( (dim(df_duet)[1] == dim(d2_duet)[1]) &
(dim(df_duet)[2] == dim(d2_duet)[2])
){
print("PASS: Dims of both dfs as expected")
} else {
print ("FAIL: Dims mismatch")
quit()}
#=========
# step 4_P1:
# VERY important
#=========
# assign it back to the pdb file
my_pdb_duet[['atom']] = df_duet
max(df_duet$b); min(df_duet$b)
table(df_duet$b)
sum(is.na(df_duet$b))
#=========
# step 5_P1
#=========
cat(paste0("output file duet mean stability pdb:", outfile_duet_mspdb))
write.pdb(my_pdb_duet, outfile_duet_mspdb)
#============================
# Add the 3rd histogram and density plots for comparisons
#============================
# Plots continued...
# Row 3 plots: hist and density of replaced B-factors with stability values
hist(df_duet$b
, xlab = ""
, main = "repalcedB duet")
plot(density(df_duet$b)
, xlab = ""
, main = "replacedB duet")
# graph titles
mtext(text = "Frequency"
, side = 2
, line = 0
, outer = TRUE)
mtext(text = paste0(tolower(gene), ": stability distribution")
, side = 3
, line = 0
, outer = TRUE)
#============================================