Thanks Anomalous, I see what you mean by backsliding- I had been testing the code with a single file to control for errors with the loop (and avoid being overwhelmed by error messages). Here is the updated code that works. I see other responses suggesting better ways to do this and potential problems with the hash, and I will address those as well. But at the moment, this works. Thanks for all your help!

#!/usr/bin/perl
use strict;
use warnings;

my %hash = ();
open my $fh, '<', 'sample_name_ID_hash.txt' or die "Cant open file $!"
+;

LINE:
while (my $line = <$fh>) 
    {
        my ($key, $value) = split /\s/, $line;
        next LINE if not $key;
        $hash{$key} = $value;
        chomp (%hash);
    }

close $fh;
        
@file_array = <*.nex> or die $!; #find all the files
foreach $file (@file_array)
    {
    my $prefix = $file;
    $prefix =~ s/\.nex//;
    open FH, "$file", or die $!;
    print "found $file with prefix $prefix\n";
    open OUT, ">out$prefix.nex" or die $!;

 while (<FH>)
          {
          if (/^\s+\'(\S+):(\S\d+)\|\w+\|(\d)\S+\'(.*)\n/)
               {
               $var1 = "$1";
               $var2 = "$2";
               $var3 = "$3";
               $var4 = "$4";
               print OUT "'$hash{$var1}_${var2}_$var3'$var4\n";
               }
            elsif (/(.*)\n/)
                {
                print OUT "$1\n";
               }
            }
     }

[download]

In reply to Re^4: In place search and replace with a hash by hkates
in thread In place search and replace with a hash by hkates

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