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It seems like the main improvement/optimization would be not looping twice through the list of all words.  Move *all* processing into the main loop:
my (%word, %gram); while (<>) { chomp; # $_ = lc $_; /[^a-z]/ and next; my $sig = pack "C*", sort unpack "C*", $_; if (exists $word{$sig}) { if (exists $gram{$sig}) { next if $gram{$sig} =~ /\b$_\b/; $gram{$sig} .= " $_"; # rare } else { next if $word{$sig} eq $_; $gram{$sig} = "$word{$sig} $_"; # rare } } else { $word{$sig} = $_; # mostly } } print join "\n", (sort values %gram), ''; # just output short list

Only the first word of an anagram set is in both lists.
Here's some more finds, mostly from the short OED from here
ablest bleats stable tables adroitly dilatory idolatry angered derange enraged grandee grenade ascertain cartesian sectarian asleep elapse please aspirant partisan attentive tentative auctioned cautioned education canoe ocean comedian demoniac compile polemic covert vector danger gander garden deist diets edits idest sited tides emits items metis mites smite times emitter termite lapse leaps pales peals pleas nastily saintly obscurantist subtractions observe obverse verbose opt pot top opts post pots spot stop tops opus soup oy yo petrography typographer peripatetic precipitate present repents serpent presume supreme resin rinse risen siren salivated validates slitting stilting tiltings titlings tlingits views wives vowels wolves woodlark workload


  p

In reply to Re: Re: Re: Perl's pearls by petral
in thread Perl's pearls by gmax

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