/usr/share/perl5/Genome/Model/Tools/Music/Smg.pm.R is in libgenome-model-tools-music-perl 0.04-3.
This file is owned by root:root, with mode 0o644.
The actual contents of the file can be viewed below.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 | #############################################
### Functions for testing significance of ###
### per-gene categorized mutation rates ###
#############################################
# Fetch command line arguments
args = commandArgs();
input_file = as.character(args[4]);
output_file = as.character(args[5]);
run_type = as.character(args[6]);
processors = as.numeric(args[7]);
skip_low_mr_genes = as.numeric(args[8]);
# See if we have the necessary packages installed to run in parallel
is.installed <- function( mypkg ) is.element( mypkg, installed.packages()[,1] );
parallel = FALSE;
if( processors > 1 & is.installed( 'doMC' ) & is.installed( 'foreach' )) {
parallel = TRUE;
}
gethist <- function( xmax, n, p, ptype = "positive_log" ) {
dbinom( 0:xmax, n, p ) -> ps;
ps = ps[ps > 0];
lastp = 1 - sum( ps );
if( lastp > 0 ) ps = c( ps, lastp );
if( ptype == "positive_log" ) ps = -log( ps );
return( ps );
}
binit <- function( x, hmax, bin, dropbin = T ) {
bs = as.integer( x / bin );
bs[bs > hmax/bin] = hmax / bin;
bs[is.na( bs )] = hmax / bin;
tapply( exp(-x), as.factor( bs ), sum ) -> bs;
bs = bs[bs>0];
bs = -log( bs );
if( dropbin ) bs = as.numeric( bs );
return( bs );
}
convolute_b <- function( a, b ) {
tt = NULL;
for( j in b ) { tt = c( tt, ( a + j )); }
return( tt );
}
mut_class_test <- function( x, xmax = 100, hmax = 25, bin = 0.001 ) {
x = as.data.frame( x );
colnames( x ) = c( "Class", "n", "x", "e" );
x$p = NA; x$lh0 = NA; x$lh1 = NA;
tot_muts = x[( x$Class == "Overall" ),]$x;
tot_bps = x[( x$Class == "Overall" ),]$n;
overall_bmr = x[( x$Class == "Overall" ),]$e;
# Remove the row containing overall MR and BMR because we don't want it to be a tested category
x = x[( x$Class != "Overall" ),];
# If user wants to skip testing genes with low MRs, measure the relevant MRs of this gene
gene_mr = 0; indel_mr = 0; indel_bmr = 0; trunc_mr = 0; trunc_bmr = 0;
if( skip_low_mr_genes == 1 ) {
if( tot_bps > 0 ) { gene_mr = tot_muts / tot_bps; }
if( x[( x$Class == "Indels" ),]$n > 0 ) { indel_mr = x[( x$Class == "Indels" ),]$x / x[( x$Class == "Indels" ),]$n; }
indel_bmr = x[( x$Class == "Indels" ),]$e;
if( nrow( x[( x$Class == "Truncations" ),] ) > 0 ) {
if( x[( x$Class == "Truncations" ),]$n > 0 ) { trunc_mr = x[( x$Class == "Truncations" ),]$x / x[( x$Class == "Truncations" ),]$n; }
trunc_bmr = x[( x$Class == "Truncations" ),]$e;
}
}
# Set pvals of 1 for genes with zero mutations, zero covered bps, or zero overall BMR
if( tot_muts <= 0 | tot_bps <= 0 | overall_bmr <= 0 ) {
p.fisher = 1; p.lr = 1; p.convol = 1; qc = 1;
}
# If user wants to skip testing genes with low MRs, give them pvals of 1
else if( skip_low_mr_genes == 1 & gene_mr < overall_bmr & indel_mr <= indel_bmr & trunc_mr <= trunc_bmr ) {
p.fisher = 1; p.lr = 1; p.convol = 1; qc = 1;
}
else {
# Skip testing mutation categories that have zero BMR, or if this gene has #muts >= #covd bps
x = x[( x$n > 0 & x$n > x$x & x$e > 0 ),];
rounded_mut_cnts = round(x$x);
for( i in 1:nrow(x) ) {
x$p[i] = binom.test( rounded_mut_cnts[i], x$n[i], x$e[i], alternative = "greater" )$p.value;
x$lh0[i] = dbinom( rounded_mut_cnts[i], x$n[i], x$e[i], log = T );
x$lh1[i] = dbinom( rounded_mut_cnts[i], x$n[i], x$x[i] / x$n[i], log = T );
ni = x$n[i]; ei = x$e[i];
gethist( xmax, ni, ei, ptype = "positive_log" ) -> bi;
binit( bi, hmax, bin ) -> bi;
if( i == 1 ) { hist0 = bi; }
if( i > 1 & i < nrow(x) ) { hist0 = convolute_b( hist0, bi ); binit( hist0, hmax, bin ) -> hist0; }
if( i == nrow(x)) { hist0 = convolute_b( hist0, bi ); }
}
# Fisher combined p-value
q = ( -2 ) * sum( log( x$p ));
df = 2 * length( x$p );
p.fisher = 1 - pchisq( q, df );
# Likelihood ratio test
q = 2 * ( sum( x$lh1 ) - sum( x$lh0 ));
df = sum( x$lh1 != 0 );
if( df > 0 ) p.lr = 1 - pchisq( q, df );
if( df == 0 ) p.lr = 1;
# Convolution test
bx = -sum( x[,"lh0"] );
p.convol = sum( exp( -hist0[hist0>=bx] ));
qc = sum( exp( -hist0 ));
}
# Return results
rst = list( x = cbind( x, tot_muts, p.fisher, p.lr, p.convol, qc ));
return( rst );
}
dotest <- function( idx, mut, zgenes ) {
step = round( length( zgenes ) / processors );
start = step * ( idx - 1 ) + 1;
stop = step * idx;
if( idx == processors ) { stop = length( zgenes ); }
tt = NULL;
for( Gene in zgenes[start:stop] ) {
mutgi = mut[mut$Gene==Gene,];
mut_class_test( mutgi[,2:5], hmax = 25, bin = 0.001 ) -> z;
tt = rbind( tt, cbind( Gene, unique( z$x[,(9:11)] )));
}
return( tt );
}
combineresults <- function( a, b ) {
return( rbind( a, b ));
}
smg_test <- function( gene_mr_file, pval_file ) {
read.delim( gene_mr_file ) -> mut;
colnames( mut ) = c( "Gene", "Class", "Bases", "Mutations", "BMR" );
mut$BMR = as.numeric( as.character( mut$BMR ));
tt = NULL;
# Run in parallel if we have the needed packages, or fall back to the old way
if( parallel ) {
library( 'doMC' );
library( 'foreach' );
registerDoMC();
cat( "Parallel backend installed - splitting across", processors, "cores\n" );
options( cores = processors );
mcoptions <- list( preschedule = TRUE );
zgenes = unique( as.character( mut$Gene ));
tt = foreach( idx = 1:processors, .combine="combineresults", .options.multicore = mcoptions ) %dopar% {
dotest( idx, mut, zgenes );
}
write.table( tt, file = pval_file, quote = FALSE, row.names = F, sep = "\t" );
}
else {
for( Gene in unique( as.character( mut$Gene ))) {
mutgi = mut[mut$Gene==Gene,];
mut_class_test( mutgi[,2:5], hmax = 25, bin = 0.001 ) -> z;
tt = rbind( tt, cbind( Gene, unique( z$x[,(9:11)] )));
}
write.table( tt, file = pval_file, quote = FALSE, row.names = F, sep = "\t" );
}
}
smg_fdr <- function( pval_file, fdr_file ) {
read.table( pval_file, header = T, sep = "\t" ) -> x;
#Calculate FDR measure and write FDR output
p.adjust( x[,2], method="BH" ) -> fdr.fisher;
p.adjust( x[,3], method="BH" ) -> fdr.lr;
p.adjust( x[,4], method="BH" ) -> fdr.convol;
x = cbind( x, fdr.fisher, fdr.lr, fdr.convol );
#Rank SMGs starting with lowest convolution test FDR, and then by Likelihood Ratio FDR
x = x[order( fdr.convol, fdr.lr ),];
write.table( x, file = fdr_file, quote = FALSE, row.names = F, sep = "\t" );
}
# Figure out which function needs to be invoked and call it
if( run_type == "smg_test" ) { smg_test( input_file, output_file ); }
if( run_type == "calc_fdr" ) { smg_fdr( input_file, output_file ); }
|