bin/llp

   1 #!/usr/local/bin/perl
   2
   3 use FindBin qw($Bin);
   4 use lib "$Bin/../lib";
   5
   6 # Don't edit the line below, it must look exactly like this.
   7 # Everything above this line will be replaced #
   8
   9 use PsN;
  10 use model;
  11 use tool::llp;
  12 use debug;
  13 use strict;
  14 use Getopt::Long;
  15 use common_options;
  16 use ui;
  17
  18 my $cmd_line = $0 . " " . join( " ", @ARGV );
  19
  20 my %options;
  21
  22 my %required_options = ( "thetas:s"=>'theta list',
  23                          "omegas:s"=>'omega list',
  24                          "sigmas:s"=>'sigma list' );
  25
  26 my %optional_options = ( "max_iterations:i" => '',
  27                          "normq:f" => '',
  28                          "outputfile:s" => '',
  29                          "ofv_increase:f" => '',
  30                          "significant_digits:i" => '',
  31                          "rse_thetas:s" => 'theta rel. SE list',
  32                          "rse_omegas:s" => 'omega rel. SE list',
  33                          "rse_sigmas:s" => 'sigma rel. SE list');
  34
  35 my $res = GetOptions( \%options,
  36                       @common_options::get_opt_strings,
  37                       keys(%required_options),
  38                       keys(%optional_options) );
  39
  40
  41 exit unless $res;
  42
  43 my %help_text;
  44
  45 $help_text{Pre_help_message} = <<'EOF';
  46     <h3 class="heading1">llp</h3>
  47
  48       Perl script for log-likelihood profiling of NONMEM runs.
  49
  50     <h3 class="heading1">Usage:</h3>
  51 EOF
  52
  53 $help_text{Description} = <<'EOF';
  54     <h3 class="heading1">Description:</h3>
  55
  56       The Log-likelihood Profiling tool can be used to assess
  57       confidence interval limits for parameter estimates. The
  58       -2*log-likelihood of hierarchical models are chi-square
  59       distributed. Fixing a parameter reduces the number of parameters
  60       of the model by one. To be able to say, for a given level of
  61       confidence, that there is a higher likelihood that the data has
  62       been produced by a system described by the full model than by one
  63       described by the reduced, the difference in the -2*log-likelihood
  64       should be at least X. For example, using a confidence level of
  65       95%, the difference (or X above) should be at least 3.84. The
  66       minimal number of arguments include a modelfile name and a
  67       listing of parameters, given that an output file with standard
  68       error estimates exist.
  69 EOF
  70
  71 $help_text{Examples} = <<'EOF';
  72     <h3 class="heading1">Example:</h3>
  73
  74       <p class="style2">llp -model=run89.mod -thetas='1,2'</p>
  75
  76       This will make the llp tool try to estimate the confidence
  77       intervals for thetas one and two of the model in run89.mod. It
  78       will base the first guesses on the standard error estimates from
  79       run89.lst.
  80
  81       <p class="style2">llp -model=run89.mod -thetas='1,2' -rse_thetas='20,30'</p>
  82
  83       In this example, we explicitly specify the relative standard
  84       errors which is necessary if we do not have an output file with
  85       standard error estimates.
  86 EOF
  87
  88 $help_text{Options} = <<'EOF';
  89     <h3 class="heading1">Options:</h3>
  90
  91       The options are given here in their long form. Any option may be
  92       abbreviated to any nonconflicting prefix. The <span class="style2">-threads</span> option
  93       may be abbreviated to <span class="style2">-t</span>(or even <span class="style2">-thr</span>) but <span class="style2">-debug</span> may not be
  94       abbreviated to <span class="style2">-d</span> because it conflicts with <span class="style2">-debug_packages</span> and
  95       <span class="style2">-debug_subroutines</span>.
  96     <br><br>
  97       The following options are valid:
  98 EOF
  99
 100 $help_text{-h} = <<'EOF';
 101       <p class="style2">-h | -?</p>
 102
 103       With -h or -? llp will print a list of options and exit.
 104 EOF
 105
 106 $help_text{-help} = <<'EOF';
 107       <p class="style2">-help</p>
 108
 109       With -help llp will print this, longer, help message.
 110 EOF
 111
 112 $help_text{-model} = <<'EOF';
 113       <p class="style2">-model='filename'</p>
 114
 115       The name of the model file. May be specified with or without the
 116       "'".
 117 EOF
 118
 119 $help_text{-outputfile} = <<'EOF';
 120       <p class="style2">-outputfile='filename'</p>
 121
 122       The name of the NONMEM output file. The default value is the
 123       name of the model file with a '.mod' substituted with
 124       '.lst'. Example: if the modelfile is run89.mod, the default name
 125       of the output file is run89.lst. If the name of the modelfile is
 126       cmd123 the default name of the output file is cmd123.lst. If the
 127       name of your output file does not follow this standard, you have
 128       to specify it with this option.
 129 EOF
 130
 131 $help_text{-thetas} = <<'EOF';
 132       <p class="style2">-thetas, -omegas, -sigmas='comma-separated list of parameter
 133       numbers'</p>
 134
 135       Specifies the parameters  for which the llp should try to assess
 136       confidence intervals.
 137 EOF
 138
 139 $help_text{-rse_thetas} = <<'EOF';
 140       <p class="style2">-rse_thetas, -rse_omegas, -rse_sigmas='comma-separated list of
 141       relative standard errors'</p>
 142
 143       The relative standard errors should be specified in percent (%).
 144 EOF
 145
 146 $help_text{-max_iterations} = <<'EOF';
 147       <p class="style2">-max_iterations=integer</p>
 148
 149       This number limits the number of search iterations for each
 150       interval limit. If the llp has not found the upper limit for a
 151       parameter after max_iteration number of guesses it
 152       terminates. The default value is 10.
 153 EOF
 154
 155     $help_text{-significant_digits} = <<'EOF';
 156       <p class="style2">-significant_digits=integer</p>
 157
 158       Specifies the number of significant digits that is required for
 159       the test of the increase in objective function value.
 160
 161 EOF
 162     $help_text{-normq} = <<'EOF';
 163       <p class="style2">-normq=number</p>
 164
 165       This number is used for calculating the first guess of the
 166       confidence interval limits. If the standard errors exist, the
 167       first guess will be
 168
 169       <p class="style2">maximum-likelihood estimate ± normq * standard error</p>
 170
 171       otherwise it will be approximated with
 172
 173       <p class="style2">maximum-likelihood estimate ± normq * rse_parameter/100 * maximum-likelihood estimate</p>
 174
 175       where rse_parameter is rse_thetas, rse_omegas or rse_sigmas. The
 176       default value is 1.96 which translates a 95% confidence interval
 177       assuming normal distribution of the parameter estimates.
 178 EOF
 179
 180     $help_text{-ofv_increase} = <<'EOF';
 181       <p class="style2">-ofv_increase</p>
 182
 183       The increase in objective function value associated with the
 184       desired confidence interval. The default value is 3.84.
 185 EOF
 186
 187     $help_text{Post_help_message} = <<'EOF';
 188       Also see 'execute -help' for a description of common options.
 189 EOF
 190
 191 common_options::online_help( 'llp', \%options, \%help_text, \%required_options, \%optional_options);
 192
 193 ## Check that we do have a model file
 194 if ( scalar(@ARGV) < 1 ) {
 195   print "At least on model file must be specified. Use 'llp -h' for help.\n";
 196   exit;
 197 }
 198
 199 if( scalar(@ARGV) > 1 ){
 200   print "LLP can only handle one modelfile. Use 'llp -h' for help.\n";
 201   exit;
 202 }
 203
 204 unless( $options{'thetas'} or $options{'omegas'} or $options{'sigmas'}){
 205   print "You must specify one of the '--thetas', '--omegas' or '--sigmas' options\n";
 206   exit;
 207 }
 208
 209 ui -> category( 'llp' );
 210 ui -> silent(1) if( $options{'silent'} );
 211
 212 debug -> level( $options{'debug'} );
 213 debug -> package( $options{'debug_package'} );
 214 debug -> subroutine( $options{'debug_subroutine'} );
 215 debug -> warn_with_trace( $options{'warn_with_trace'} );
 216
 217 my @thetas = split( ',',$options{'thetas'} );
 218 my @omegas = split( ',',$options{'omegas'} );
 219 my @sigmas = split( ',',$options{'sigmas'} );
 220 my @rse_thetas = split( ',',$options{'rse_thetas'} );
 221 my @rse_omegas = split( ',',$options{'rse_omegas'} );
 222 my @rse_sigmas = split( ',',$options{'rse_sigmas'} );
 223
 224 my ( %checked_rse_thetas, %checked_rse_omegas, %checked_rse_sigmas );
 225
 226 foreach my $param ( 'thetas', 'omegas', 'sigmas' ) {
 227   my $nse = eval('$#rse_'.$param)+1;
 228   if ( $nse > 0 ) {
 229     my $npa = eval('$#'.$param)+1;
 230     die "The number of $param ($npa) does not match the number of relative standard errors ($nse)\n"
 231       if ( not $npa == $nse );
 232     for ( my $i = 0; $i < $npa; $i++ ) {
 233       eval( '$checked_rse_'.$param.'{$'.$param.'['.$i.']} = $rse_'.$param."[$i]" ),"\n";
 234     }
 235   }
 236 }
 237
 238 my $eval_string = common_options::model_parameters(\%options);
 239
 240 my $model = model -> new ( eval( $eval_string ),
 241                            filename                    => $ARGV[0],
 242                            debug                       => $options{'debug'},
 243                            ignore_missing_output_files => 1);
 244
 245 ## Create new Llp object:
 246 my $llp = tool::llp ->
 247   new ( eval( $common_options::parameters ),
 248         max_iterations     => $options{'max_iterations'},
 249         models             => [ $model ],
 250         normq              => $options{'normq'},
 251         ofv_increase       => $options{'ofv_increase'},
 252         significant_digits => $options{'significant_digits'},
 253         run_thetas         => \@thetas,
 254         run_omegas         => \@omegas,
 255         run_sigmas         => \@sigmas,
 256         rse_thetas         => \%checked_rse_thetas,
 257         rse_omegas         => \%checked_rse_omegas,
 258         rse_sigmas         => \%checked_rse_sigmas );
 259
 260 open(CMD, ">", $llp -> directory . "/command.txt");
 261 print CMD $cmd_line, "\n";
 262 close(CMD);
 263
 264 $llp -> run;
 265 $llp -> print_results;
 266