How to get sequence variant information from no dbSNP using ensembl Perl API.

Question

[francisco.abad]

Hi, this is my first post. I'm Fran from Spain and currently I'm working on my final thesis for a bioinformatic master's degree. I have to obtain transcript sequences which are affected by a mutation. To do this, firstly I get the original sequence of the transcript and then I include the mutation by modifing the string.

I use the following function in order to perform the operation:

# param 0 -> TransciptVariationAllele object
# return -> Sequence of the variation including 5' and 3' regions.
sub get_variation_seq{
    my $tva = $_[0];
    # translateable_seq returns the coding part of the transcript
    # (it removes introns and 5' and 3' utr)
    # my $seq = $tva->transcript->translateable_seq;
    # seq contains 5' and 3' regions.
    my $seq = $tva->transcript->seq->seq;
    my $variation_start = $tva->transcript_variation->cdna_start - 1;
    my $variation_end = $tva->transcript_variation->cdna_end - 1;
    # If is a deletion, feature_seq is '-', so we will use '' instead
    # to build the final sequence.
    my $feature_seq = $tva->feature_seq eq "-" ? "" : $tva->feature_seq;

    print $tva->display_codon_allele_string . "\n";
    print $tva->transcript_variation->variation_feature->variation_name . "\t$variation_start-$variation_end\n";
    print "$seq\n";
    substr($seq, $variation_start, $variation_end - $variation_start + 1) = $feature_seq;
    print $seq . "\n";

    return $seq;
}

This function receives a TrancriptVariationAllele object and returns the complete variation sequence, including 5' and 3' UTR. This works for dbSNP variations, but when I have to deal with COSMIC or HGMD-PUBLIC variations, $tva->feature_seq does not contain information about the variation seq, it only contains a string as "COSMIC".

¿How could I get the complete mutated sequence of non dbSNP variations? ¿Is there any other way to do this?

Thank you in advance.

Greeting, Fran.

Answer 1

[Emily]

Unfortunately many variants from COSMIC and HGMD are not distributed with alleles, just the loci.

[francisco.abad]

Thanks for your answer, Emily. In that case I would have to exclude variations whose source is different from dbSNP.