Hello again, corcra,

I’m glad to have been of help.

If I understand you correctly, you now want read the data headings, say:

Field:    0            5            6            7            8
File 1: ['CHROM', ... 'SAMPLE_1A', 'SAMPLE_1B', 'SAMPLE_2A', 'SAMPLE_2
+B']
File 2: ['CHROM', ... 'SAMPLE_1',  'SAMPLE_2',  'SAMPLE_3']
[download]

and have the script deduce that File 1 data in fields 5 and 6 should each be compared to File 2 field 5, File 1 data in fields 7 and 8 should each be compared to File 2 field 6, and so on.

That makes the logic more complex, but I don’t know why you think this will be difficult to do line-by-line? Most of the added logic comes before the big while loop:

...
my $header1 = <$in1>;
<$in2>;
my @heads1  = split /\s*,\s*/, $header1;
my $index   = 5;
my %index_map;

for (@heads1)
{
    $index_map{$index++} = $1 + 4 if /SAMPLE_(\d+)/;
}

print $header1;

while (my $line1 = <$in1>)
{
    my @fields1 = get_fields($line1);

    defined(my $line2 = <$in2>)
        or die "Data missing in file '$file2': $!";

    my @fields2 = get_fields($line2);
    my @out     = @fields1;

    for my $i (5 .. $#fields1)
    {
        if ($fields1[$i] ne 'REF')
        {
            my $j    = $index_map{$i};
            $out[$i] = $fields2[$j] if exists $fields2[$j] &&
                                              $fields2[$j] ne 'REF';
        }
    }
    
    @out = map { "'$_'" } @out;
    print '[', join(', ', @out), "]\n";
}
...
[download]

The main addition is a hash (%index_map) to keep track of the correspondences between the fields in File 1 and the matching fields in File 2.

Hope that helps,