Hi Bram,<div><br></div><div>You're not alone in wondering about these more complex variation types!</div><div><br></div><div>While the software does support them (provided you get the input format right!), the results may not always reflect the complexity, as the consequence types we currently return do not cover all possible events. You can however get a good sense of what is happening by carefully considering what is returned by the coordinate methods (cds_start, cds_end, cdna_start, cdna_end, translation_start, translation_end) and the pep_allele_string() and codons() methods.</div>
<div><br></div><div>In determining the input format, you need to consider what region of the reference sequence is being affected, and what is replacing the reference. I would input this variant as:</div><div><font class="Apple-style-span" face="'courier new', monospace"><br>
</font></div><div><font class="Apple-style-span" face="'courier new', monospace"> 1 2 3 4 5 6 7</font></div><div><meta charset="utf-8"><div><font class="Apple-style-span" face="'courier new', monospace">ref:<span style="white-space: pre-wrap; "> </span>A C G T A G A</font></div>
<div><font class="Apple-style-span" face="'courier new', monospace">var:<span style="white-space: pre-wrap; "> </span>A C A - - G A</font></div></div><div><font class="Apple-style-span" face="'courier new', monospace"><br>
</font></div><div><font class="Apple-style-span" face="arial, helvetica, sans-serif">You could view this as a SNP and a deletion (two events, as you describe), or as an unbalanced substitution (one event)</font></div><div>
<font class="Apple-style-span" face="arial, helvetica, sans-serif"><br></font></div><div><font class="Apple-style-span" face="arial, helvetica, sans-serif">As two events, this would have input (assuming chromosome 1 and coords as above for simplicity):</font></div>
<div><font class="Apple-style-span" face="arial, helvetica, sans-serif"><br></font></div><div><font class="Apple-style-span" face="arial, helvetica, sans-serif">1 3 3 G/A +</font></div><div><font class="Apple-style-span" face="arial, helvetica, sans-serif">1 4 5 TA/- +</font></div>
<div><font class="Apple-style-span" face="arial, helvetica, sans-serif"><br></font></div><div><font class="Apple-style-span" face="arial, helvetica, sans-serif">As one event, which is how I would input this variation:</font></div>
<div><font class="Apple-style-span" face="arial, helvetica, sans-serif"><br></font></div><div><font class="Apple-style-span" face="arial, helvetica, sans-serif">1 3 5 GTA/A +</font></div><div><font class="Apple-style-span" face="arial, helvetica, sans-serif"><br>
</font></div><div><font class="Apple-style-span" face="arial, helvetica, sans-serif">So we are substituting GTA (bases 3-5 of the reference) with A.</font></div><div><font class="Apple-style-span" face="arial, helvetica, sans-serif"><br>
</font></div><div><font class="Apple-style-span" face="arial, helvetica, sans-serif">Although (and I guess this isn't a real example!), a better alignment would surely be:</font></div><div><font class="Apple-style-span" face="arial, helvetica, sans-serif"><meta charset="utf-8"><span class="Apple-style-span" style="font-family: arial; "><div>
<font class="Apple-style-span" face="'courier new', monospace"><br class="Apple-interchange-newline"> 1 2 3 4 5 6 7</font></div><div><div><font class="Apple-style-span" face="'courier new', monospace">ref:<span style="white-space: pre-wrap; "> </span>A C G T A G A</font></div>
<div><font class="Apple-style-span" face="'courier new', monospace">var:<span style="white-space: pre-wrap; "> </span>A C - - A G A</font></div></div></span></font></div><div><br></div><div>where there's just one deletion event of bases 3 & 4. But that's just nit-picking!</div>
<div><br></div><div>Hope this helps anyway</div><div><br></div><div>Cheers</div><div><br></div><div>Will McLaren</div><div>Ensembl Variation</div><div><br></div><div><br><div class="gmail_quote">On 14 December 2010 15:42, Bram De Wilde <span dir="ltr"><<a href="mailto:gbramdewilde@gmail.com">gbramdewilde@gmail.com</a>></span> wrote:<br>
<blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex;"><div style="word-wrap:break-word">Hi everyone,<div><br></div><div>While unraveling the complex variants that can be encoded in the vcf format (<a href="http://www.1000genomes.org/wiki/Analysis/Variant%20Call%20Format/vcf-variant-call-format-version-40" target="_blank">http://www.1000genomes.org/wiki/Analysis/Variant%20Call%20Format/vcf-variant-call-format-version-40</a>) I came to realize that I don't know how to submit some of these complex alleles to the ensembl variation API for effect prediction.</div>
<div>For simple SNP's and indels the situation is clearly described in the help pages. The problem I seem to be having is with complex alleles:</div><div><br></div><div>eg. when a SNP is directly followed by an deletion on a chromosome z</div>
<div>ref:<span style="white-space:pre-wrap"> </span>ACGTAGA</div><div>var:<span style="white-space:pre-wrap"> </span>ACA--GA</div><div><br></div><div>this can be encoded as 2 variants:</div><div>chr<span style="white-space:pre-wrap"> </span>start<span style="white-space:pre-wrap"> </span>stop<span style="white-space:pre-wrap"> </span>variant<span style="white-space:pre-wrap"> </span>strand</div>
<div>z<span style="white-space:pre-wrap"> </span>3<span style="white-space:pre-wrap"> </span>3<span style="white-space:pre-wrap"> </span>G/A<span style="white-space:pre-wrap"> </span>+</div><div>z<span style="white-space:pre-wrap"> </span>4<span style="white-space:pre-wrap"> </span>5<span style="white-space:pre-wrap"> </span>TA/-<span style="white-space:pre-wrap"> </span>+</div>
<div>but clearly none of these will have the functional consequence of the true allele namely:</div><div>z<span style="white-space:pre-wrap"> </span>3<span style="white-space:pre-wrap"> </span>5<span style="white-space:pre-wrap"> </span>GTA/A<span style="white-space:pre-wrap"> </span>+</div>
<div><span style="white-space:pre-wrap">unfortunately</span> this kind of allele does not seem to return any response from the variation API</div><div><span style="white-space:pre-wrap"><br></span></div><div>I can think of a simmilar situation for an insertion:</div>
<div><div>ref:<span style="white-space:pre-wrap"> </span>ACG-TAGA</div><div>var:<span style="white-space:pre-wrap"> </span>ACACTAGA</div></div><div><br></div><div>where:</div><div><div>chr<span style="white-space:pre-wrap"> </span>start<span style="white-space:pre-wrap"> </span>stop<span style="white-space:pre-wrap"> </span>variant<span style="white-space:pre-wrap"> </span>strand</div>
<div>z<span style="white-space:pre-wrap"> </span>3<span style="white-space:pre-wrap"> </span>3<span style="white-space:pre-wrap"> </span>G/A<span style="white-space:pre-wrap"> </span>+</div><div>z<span style="white-space:pre-wrap"> </span>4<span style="white-space:pre-wrap"> </span>3<span style="white-space:pre-wrap"> </span>-/C<span style="white-space:pre-wrap"> </span>+</div>
</div><div>will not have the same consequence as</div><div>z<span style="white-space:pre-wrap"> </span>4<span style="white-space:pre-wrap"> </span>3<span style="white-space:pre-wrap"> </span>G/AC<span style="white-space:pre-wrap"> </span>+</div>
<div><br></div><div><br></div><div>Or do I see this all wrong?</div><div>is there a way to submit alleles like these for effect prediction?</div><div><br></div><div><br></div><div>Kind regards,</div><div><br></div><font color="#888888"><div>
<span style="border-collapse:collapse;font-family:arial, sans-serif;font-size:13px;white-space:pre-wrap"><br></span></div><div><span style="border-collapse:collapse;font-family:arial, sans-serif;font-size:13px;white-space:pre-wrap">Bram De Wilde, MD</span></div>
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