OK, so here's an interesting tidbit. I tried out your modifications to my WEED() sub, and it wound up doubling the time it took to run! Weird. Heres the (truncated) dprof output of my original sub:
Total Elapsed Time = 1135.701 Seconds
  User+System Time = 770.4718 Seconds
Exclusive Times
%Time ExclSec CumulS #Calls sec/call Csec/c  Name
 63.8   491.8 491.86      1   491.86 491.86  main::WEED
 32.5   251.1 251.10  22012   0.0114 0.0114  main::SEARCHFASTA
 2.10   16.20 16.209    164   0.0988 0.0988  main::GET_TEXT
 0.71   5.460  5.460      1   5.4600 5.4600  main::INDEX_FASTA
 0.40   3.089  3.089    164   0.0188 0.0188  main::ADD_SPAN
 0.15   1.140  1.140      1   1.1400 1.1400  main::WEEDNUM
 (......)

[download]

And here's the output with the modifications you suggested:

Total Elapsed Time = 1292.196 Seconds
  User+System Time = 1200.096 Seconds
Exclusive Times
%Time ExclSec CumulS #Calls sec/call Csec/c  Name
 76.9   923.0 923.08      1   923.08 923.08  main::WEED
 20.6   247.6 247.61  22012   0.0112 0.0112  main::SEARCHFASTA
 1.30   15.57 15.579    164   0.0950 0.0950  main::GET_TEXT
 0.60   7.240  7.240      1   7.2400 7.2400  main::INDEX_FASTA
 0.17   2.059  2.059    164   0.0126 0.0126  main::ADD_SPAN
 0.14   1.729  3.848      1   1.7292 3.8483  main::HTML_FORMAT
(......)

[download]

So, I am guessing that the grep wound up being less efficient than the 'band pass' filter I had set up. Weird. That said, I have not yet tried a combination of our two different methods. I have a feeling most of your comments are going to wind up helping, but that in this case, the nature of the data just lends itself better to the filter approach.

I hope that I can still shed significant time off of this sub, so I'll post it to the "Seekers of Perl Wisdom" forum for additional help.

Thank you so much though for taking the time to try and help me fix this. I really appreciate it.

Matt

In reply to Re^6: Refactoring a large script by mdunnbass
in thread Refactoring a large script by mdunnbass

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