Hi, johngg, I rather tried to communicate that all contestants should be placed in equal conditions, i.e. let them all read in chunks, rather than in single lines, as it was for some of them. But all the same your "ANDmask" is fastest.

Which is weird. Simple act of extracting some part of data, instead of just indexing, requires, to be fast, modification of unrelated data. Sure, it's because of speed of "anding" and transliteration, but still... Therefore, here is something completely different (sorry I keep adjusting your setup to suite my "dna.txt"):

use strict;
use warnings;

use Benchmark  qw{ cmpthese timethese };
use Test::More qw{ no_plan };

use String::Random 'random_regex';
my $fn  = 'dna.txt';

unless ( -e $fn ) {
    open my $fh, '>', $fn;
    print $fh random_regex( '[ACTG]{42}' ), "\n"
        for 1 .. 1e6;
}

open my $inFH, q{<}, $fn or die $!;
binmode $inFH;

my $buffer    = <$inFH>;
my $lineLen   = length $buffer;
my $nLines    = 500;
my $chunkSize = $lineLen * $nLines;
my $offset    = 9;    # Column 10 if numbering from 1

my %methods = (
     ANDmask => sub { # Multi-line AND mask by johngg
       seek $inFH, 0, 0;
    
       my $retStr;
       my $mask
          = qq{\x00} x ${offset}
          . qq{\xff}
          . qq{\x00} x ( $lineLen - $offset - 1 );
       $mask x= $nLines;
       while ( my $bytesRead = read $inFH, $buffer, $chunkSize )
       {
           ( my $anded = $buffer & $mask ) =~ tr{\x00}{}d;
           $retStr .= $anded;
       }
    
       return \ $retStr;
    },
    
    pdl => sub {
        seek $inFH, 0, 0;
        
        use PDL;

        my $retStr;
        my $chunkPDL = zeroes( byte, $lineLen, $nLines );
        my $bufRef   = $chunkPDL-> get_dataref;
        while ( my $bytesRead = read $inFH, $$bufRef, $chunkSize ) {
            my $lastLine = $bytesRead / $lineLen - 1;
            $retStr .= ${ $chunkPDL-> slice( "$offset,0:$lastLine" )
                                  -> get_dataref }
        }
        return \ $retStr;
    },
);

ok ${ $methods{ ANDmask }-> ()} eq ${ $methods{ pdl }-> ()};

cmpthese( -10, { 
    map {
        $_ => $methods{ $_ }
    } keys %methods
});
[download]

>perl vert5.pl
ok 1
          Rate ANDmask     pdl
ANDmask 7.86/s      --    -55%
pdl     17.3/s    120%      --
1..1
[download]