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<div class="document" id="last-performance-tuning">
<h1 class="title">LAST Performance Tuning</h1>

<p>This document tells you how to trade-off <strong>speed</strong>, <strong>sensitivity</strong>,
and <strong>memory and disk usage</strong>.</p>
<p>Ideally, the default settings would always work well.  Unfortunately,
there is too great a variety of challenging alignment tasks, and the
LAST developers lack experience with most of them.</p>
<p>LAST must have <em>some</em> defaults, and any choice will displease someone.
It is wrong to say &quot;LAST is faster but less sensitive than method X&quot;,
or &quot;slower but more sensitive than method Y&quot;, without varying the
defaults.</p>
<div class="section" id="sparsity-options">
<h2>Sparsity options</h2>
<p>It's advisable to use at most one sparsity option: combining them will
likely give poor sensitivity.</p>
<div class="section" id="lastal-k">
<h3>lastal -k</h3>
<p>By default lastal looks for initial matches starting at every position
in the query sequence(s), but -k2 makes it check every 2nd position,
-k3 every 3rd position, etc.  Compared to the other sparsity options,
this <strong>increases speed</strong> the most while <strong>reducing sensitivity</strong> the
least.</p>
</div>
<div class="section" id="lastdb-w">
<h3>lastdb -w</h3>
<p>By default lastdb indexes every position in the reference sequence(s),
but -w2 makes it index every 2nd position, -w3 every 3rd position,
etc.  Compared to the other sparsity options, this <strong>decreases memory
and disk use</strong> the most while reducing sensitivity the least.</p>
<p>This has a complex effect on the speed and sensitivity of lastal.
LAST uses initial matches that are sufficiently rare: this option
makes it lose some matches (because those positions are not indexed),
but gain others (because they are rarer).  In practice, small values
of w (e.g. 2) sometimes make lastal slower and more sensitive, but
very large values will eventually reduce sensitivity.</p>
<p>Among other aligners, MegaBLAST indexes every 5th position, and BLAT
indexes every 11th position.</p>
</div>
<div class="section" id="id1">
<h3>lastdb -W</h3>
<p>This makes LAST check for initial matches starting at only some
positions, in both query and reference.  This <strong>decreases memory and
disk use</strong>, and <strong>increases speed</strong> of lastdb and lastal, but
<strong>reduces sensitivity</strong>.</p>
<p>Specifically, this makes LAST look for initial matches starting only
at positions that are &quot;minimum&quot; in any window of W consecutive
positions.  &quot;Minimum&quot; means that the sequence starting here is
alphabetically earliest.</p>
<p>The fraction of positions that are &quot;minimum&quot; is roughly: 2 / (W + 1).</p>
</div>
</div>
<div class="section" id="lastdb8-lastal8">
<h2>lastdb8 &amp; lastal8</h2>
<p>If your reference has more than about 4 billion letters, 8-byte LAST
<em>may</em> be beneficial.  Ordinary (4-byte) LAST cannot directly handle so
much data, so it splits it into volumes, which is inefficient.  8-byte
LAST can handle such data without voluming, but it uses more memory.</p>
<p>8-byte LAST combines well with lastdb option -w or -W, which reduce
memory usage.  Something like <tt class="docutils literal">lastdb8 <span class="pre">-W63</span></tt> enables rapid,
huge-scale homology search, with moderate memory usage, but low
sensitivity.</p>
</div>
<div class="section" id="other-options">
<h2>Other options</h2>
<div class="section" id="lastal-m">
<h3>lastal -m</h3>
<p>This option <strong>trades speed for sensitivity</strong>.  It sets the rareness
limit for initial matches: initial matches are lengthened until they
occur at most this many times in the lastdb volume.  The default is
10.  So -m100 makes it more sensitive but slower, by using more
initial matches.</p>
</div>
<div class="section" id="lastal-l">
<h3>lastal -l</h3>
<p>This option makes lastal <strong>faster</strong> but <strong>less sensitive</strong>.  It sets
the minimum length of initial matches, e.g. -l50 means length 50.
(The default is 1).  This can make it <em>much</em> faster, and the
sensitivity is adequate if the alignments contain long, gapless,
high-identity matches.</p>
</div>
<div class="section" id="lastal-c">
<h3>lastal -C</h3>
<p>This option (gapless alignment culling) can make lastal <strong>faster</strong> but
<strong>less sensitive</strong>.  It can also <strong>reduce redundant output</strong>.  For
example, -C2 makes it discard alignments (before gapped extension)
whose query coordinates lie in those of 2 or more stronger alignments.</p>
</div>
<div class="section" id="lastal-x">
<h3>lastal -x</h3>
<p>This option can make lastal <strong>faster</strong> but <strong>less sensitive</strong>.  It
sets the maximum score drop in alignments, in the gapped extension
phase.  Lower values make it faster, by quitting unpromising
extensions sooner.  The default aims at best accuracy.</p>
<p>Unfortunately, the default is a complex function of the other
parameters and the database size.  You can see it in the lastal header
after &quot;x=&quot;, e.g. by running lastal with no queries.  Then try, say,
halving it.</p>
</div>
<div class="section" id="id2">
<h3>lastal -M</h3>
<p>This option requests &quot;minimum-difference&quot; alignment, which is <strong>faster
but cruder</strong> than standard gapped alignment.  This treats all matches
the same, and minimizes the number of differences (mismatches plus
gaps).</p>
</div>
<div class="section" id="lastal-j1">
<h3>lastal -j1</h3>
<p>This option requests <strong>gapless</strong> alignment, which is even <strong>faster</strong>.
(You could get the same effect by using very high gap costs, but -j1
is faster because it skips the gapping phase entirely.)</p>
</div>
<div class="section" id="lastal-f">
<h3>lastal -f</h3>
<p>Option -fTAB <strong>reduces the output size</strong>, which can improve speed.</p>
</div>
<div class="section" id="lastdb-i">
<h3>lastdb -i</h3>
<p>This option <strong>makes lastdb faster</strong>, but disables some lastal options.
If lastdb is too slow, try -i10.</p>
</div>
<div class="section" id="lastdb-c2">
<h3>lastdb -C2</h3>
<p>This option may make lastal a bit <strong>faster</strong>, but <strong>uses more memory
and disk</strong>, and makes lastdb slower.  If these downsides are no
problem, you may as well try it.</p>
</div>
<div class="section" id="repeat-masking">
<h3>Repeat masking</h3>
<p>This can make LAST <strong>much faster</strong>, produce <strong>less output</strong>, and
reduce memory and disk usage.  Please see <a class="reference external" href="last-repeats.html">last-repeats.html</a>.</p>
</div>
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