[ensembl-dev] Speeding up Bio::DB::Fasta::subseq (was Re: Thoughts on Speeding up the Variant Effect Predictor)

[Rocky Bernstein]

Just a follow-up to my earlier post.

I ran a Variant Effect Prediction  run on a VCF file of 5000 entries (which
is what fits in one buffer read)  with one small change. With that, I was
able to significantly significantly reduce the time bottleneck in the Fasta
code. The time spent here went from 7.76 seconds to 2.32 seconds.

Compare the top line of:
http://dustyfeet.com:8001/VEP-prof-5000/Bio-DB-Fasta-pm-323-line.html
with:
http://dustyfeet.com:8001/VEP-prof-5000-Inline-C/Bio-DB-Fasta-pm-323-line.html

You get a 50% reduction just by the fact that one transformation is needed
to remove both \n and \r rather than two transformations. But even beyond
this, the C code for one run is still faster than the corresponding Perl
s///.

The specific change that I made can be found at
https://gist.github.com/rocky/61f929d58a286189a758#file-fasta-pm-diff
You'll also see benchmarks for other variations of that code.

But.... in order to see the effect in a run you need to have Perl module
Inline::C installed. Otherwise you get a lesser improvement outlined in my
original posting.  Again this speeds things up by compiling once Perl
regular expressions used to match \n and \r.

In the spirit of open scientific review, I am curious to learn of others
experience the same kind of improvement I saw.

I have a pull request for this change to the bioperl-live repository. See
https://github.com/bioperl/bioperl-live/issues/95 . However I note that the
Bio::DB code used by  Variant Effect Predictor is a different (back-level)
from the code in that git repository. The diff file in the gist cited above
is for the Fasta.pm code that is in Ensembl ; of course, the pull request
uses the current Bio::DB code.


Lastly http://dustyfeet.com:8001 has the profile results other kinds of
runs which I hope will clarify my other remarks about where things are
slow.


On Thu, Dec 18, 2014 at 12:48 AM, Rocky Bernstein <rocky.bernstein at gmail.com
> wrote:
>
> Running the Variant Effect Predictor on a Human Genome VCF file (130780
> lines)  with a local Fasta cache (--offline) takes about 50 minutes on a
> quad-core Ubuntu box.
>
> I could give more details, but I don't think they are that important.
>
> In looking at how to speed this up, it looks like VEP goes through the VCF
> file,  is sorted by chromosome, and processes each
> Chromosome independently. The first obvious way to speed this up would be
> to do some sort of 24-way map/reduce.
> There is of course the --fork option on the variant_effect_predictor.pl
> program which is roughly the same idea, but it parallelizes only across the
> cores of a single computer rather than make use of multiple ones.
>
> To pinpoint the slowness better, I used Devel::NYTProf. For those of you
> who haven't used it recently, it now has flame graphs and it makes it very
> easy to see what's going on.
>
> The first thing that came out was a slowness in code to remove carriage
> returns and line feeds. This is in Bio::DB::Fasta ::subseq:
>
>      $data =~ s/\n//g;
>      $data =~ s/\r//g;
>
> Compiling the regexp, e.g:
>
>      my $nl = qr/\n/;
>      my $cr = qr/\r/;
>
>      sub subseq {
>          ....
>         $data =~ s/$nl//g;
>         $data =~ s/$cr//g;
>      }
>
> Speeds up the subseq method by about 15%. I can elaborate more or describe
> the other methods I tried and how they fared, if there's interest. But
> since this portion is really part of BioPerl and not Bio::EnsEMBL, I'll try
> to work up a git pull request ont that repository.
>
> So now I come to the meat of what I have to say. I should have put this at
> the top -- I hope some of you are still with me.
>
> The NYTProf graphs seem to say that there is a *lot* of overhead in object
> lookup and type testing. I think some of this is already known as there
> already are calls to "weaken" and "new_fast" object creators. And there is
> this comment in
>  Bio::EnsEMBL::Variation::BaseTranscriptVariation:_intron_effects:
>
>
>     # this method is a major bottle neck in the effect calculation code so
>     # we cache results and use local variables instead of method calls
> where
>     # possible to speed things up - caveat bug-fixer!
>
> In the few cases guided by NYTProf, I've been able to make reasonable
> speed ups at the expense of eliminating the tests
> and object overhead.
>
> For example, in EnsEMBL::Variation::BaseTranscriptVariation changing:
>
>
>  sub transcript {
>      my ($self, $transcript) = @_;
>      assert_ref($transcript, 'Bio::EnsEMBL::Transcript') if $transcript;
>      return $self->SUPER::feature($transcript, 'Transcript');
> }
>
> to:
>
>      sub transcript {
>          my ($self, $transcript) = @_;
>         return $self->{feature};
>
> Gives a noticeable speed up. But you may ask: if that happens, then we
> lose type safety and there is a potential for bugs?
> And here's my take on how to address these valid concerns. First, I think
> there could be two sets of the Perl modules, such as for
> EnsEMBL::Variation::BaseTranscriptVariation - those with all of the checks
> and those that are fast.  A configuration parameter might specify which
> version to use. In development or by default, one might use the ones that
> check types.
>
> Second and perhaps more import, there are the tests! If more need to be
> added, then let's add them. And one can always add a test to make sure the
> results of the two versions gives the same result.
>
> One last avenue of optimization that I'd like to explore is using say
> Inline::C or basically coding in C hot spots. In particular, consider
> Bio::EnsEMBL::Variation::Utils::VariationEffect::overlap which looks like
> this:
>
>          my ( $f1_start, $f1_end, $f2_start, $f2_end ) = @_;
>          return ( ($f1_end >= $f2_start) and ($f1_start <= $f2_end) );
>
> I haven't tried it on this hot spot, but this is something that might
> benefit from getting coded in C. Again the trade off for speed here is a
> dependency on compiling C. In my view anyone installing this locally or
> installing CPAN modules probably already does, but it does add complexity.
>
> Typically, this is handled in Perl by providing both versions, perhaps as
> separate modules.
>
> Thought or comments?
>
> Thanks,
>    rocky
>
>
>
>
>
>
>
>
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>
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