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<body>
<div class="document" id="last-and-repeats">
<h1 class="title">LAST and repeats</h1>
<p>Biomolecule sequences are full of repeats, which have a massive effect
on sequence comparison. There are two different things called
"repeats":</p>
<ul>
<li><p class="first">Interspersed repeats, such as LINEs, Alus, transposons.</p>
</li>
<li><p class="first">Simple sequence / low-complexity sequence / tandem repeats, such as
atatatatatatatatat.</p>
</li>
</ul>
<p>They cause two different problems:</p>
<ul>
<li><p class="first">Simple tracts cause alignments of sequences that are not homologous
(not descended from a common ancestor), because similar simple
sequences can evolve independently.</p>
</li>
<li><p class="first">Both kinds of repeat can make sequence comparison very slow, and
produce an overwhelming number of alignments.</p>
</li>
</ul>
<div class="section" id="last-options">
<h2>LAST options</h2>
<p>LAST has built-in recognition of simple sequences, but not (yet)
interspersed repeats. So you may wish to annotate interspersed
repeats with a tool such as RepeatMasker or WindowMasker. You can
often obtain pre-masked genomes, with repeats indicated by lowercase.</p>
<p>LAST's built-in simple-sequence masking uses <a class="reference external" href="http://cbrc3.cbrc.jp/~martin/tantan/">tantan</a>, which prevents
non-homologous alignments more reliably than previous methods.</p>
<p>To mask all kinds of repeat, use lastdb -cR11:</p>
<blockquote>
This keeps lowercase in the input sequences, additionally lowercases
simple tracts found by tantan, and masks lowercase during alignment.</blockquote>
<p>To mask simple tracts only, use lastdb -cR01:</p>
<blockquote>
This does not keep lowercase in the input sequences, lowercases
simple tracts found by tantan, and masks lowercase during alignment.</blockquote>
<p>In LAST, "mask" means that lowercase is excluded when finding similar
sequences, but included when making the final alignments.</p>
</div>
<div class="section" id="orthology-search-and-post-masking">
<h2>Orthology search and post-masking</h2>
<p>Sometimes we wish to find orthologs but not paralogs: e.g. if we
compare two whole genomes, or align DNA reads to a genome. Masking
can cause false positives, if an ortholog is masked but a paralog is
not.</p>
<p>We'd like to avoid this problem, but also avoid non-homologous
alignments of simple sequences. This can be done by post-masking:</p>
<ol class="arabic">
<li><p class="first">Align using lastdb -R01: this does not keep lowercase in the input
sequences, lowercases simple tracts found by tantan, but does not
mask it (i.e. case has no effect).</p>
</li>
<li><p class="first">Predict orthologs, e.g. using <a class="reference external" href="last-split.html">last-split</a>.</p>
</li>
<li><p class="first">Discard mostly-lowercase alignments, using <a class="reference external" href="last-postmask.html">last-postmask</a>.</p>
</li>
</ol>
</div>
</div>
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