cbizon
commented
8 years ago This is a really interesting example. when we made the first version of this model, we assumed that amino acid alleles were really a different entity from genomic alleles, because multiple genomic alleles would lead to the same AA allele. But, we thought, the same was not the case for genomic and transcript alleles. This is a good counter-example to that last point. In fact, there are two genomic alleles that are clearly distinct that are indistinguishable when viewed at the transcript level.
So what to do about it? I propose a short-term/long-term split, but I am far from sure that this is the correct answer:
Short term: The canonicalizer should treat the transcript alleles as different, each canonicalizing to its genomic allele, but not to each other. This is clearly non-optimal, but I think it's the best we can do without the long-term solution.
Long term: Incorporate transcript/genome mappings into the allele model, and break out transcript alleles as a separate entity. In this view, canonicalizing will only be done within each layer, and the projections to other layers will be to separate entities.
larrybabb
rrfreimuth
There is an issue we found during canonicalization. It may take place when deletion or insertion occurs next to splicing site. In this case one canonical allele on the transcript level may correspond to two canonical alleles on the genome level. Please, look at the following image for an example.