Survey: help define Gencode and NCBI primary transcripts

[GenoMax]

Cross-posting this here since it will be of interest. Likely to remain open for 1 week.

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Ensembl and NCBI have been working to align the GENCODE and RefSeq reference transcripts. As part of that effort, we are also developing plans to define a primary transcript for every gene as well as a minimal set of clinically relevant transcripts. To guide that effort, we have developed a small survey to get input on how to define the primary transcript and whether this would be important to your work.

The survey should only take 10 minutes or less and you will have the opportunity to sign up for follow-up info about this project if you are interested.

https://goo.gl/forms/OjEXtYGt1pxcukqp1

[r.rosati]

...Excuse me for my ignorance, but exactly, what is the issue they're trying to address by deciding to implement a clinically-driven primary transcript?

[Richard Finney]

Some Spanish researchers publish a "principal isoforms" database:

http://appris.bioinfo.cnio.es/#/

From their paper ( https://academic.oup.com/nar/article/46/D1/D213/4561658 .
APPRIS 2017: principal isoforms for multiple gene sets ) :
APPRIS selects a single protein isoform, the ‘principal’ isoform, as the reference for each gene based on these annotations. A single main splice isoform reflects the biological reality for most protein coding genes and APPRIS principal isoforms are the best predictors of these main proteins isoforms.

So ... "biological reality".

[r.rosati]

I humbly disagree. In my opinion, the biological reality is that genes encode multiple isoforms; naming an isoform as "principal" is an artificial layer which we apply to the "biological reality" to simplify it. The simplification might prove handy, but since the survey explicitly mentions clinically relevant variants as a means to selecting the principal isoform, I'm worried that the simplification might be used instead of the actual biological reality by unwary users in a human health setting.
The APPRIS paper by Rodriguez selects a reference isoform according to its conservation among species, which is a very valid take. I beg to think that this is a different take than the one presented in the survey.

[GenoMax]

NCBI/Ensembl want to make sure that there is one authoritative source of clinically important transcripts since they want clinicians to use it.

I think we can use a single longest/most abundant unique transcript per gene set for casual use (someone doing a round of RNAseq) and then multiple additional sets that cater to special needs (clinicians interested in validated SNPs, tissue specific expression etc).

[Emily_Ensembl]

This is the aim of the survey. As the clinical community frequently request something like a primary transcript, we are looking to define if this is generally wanted by the community (or just a vocal minority), what people would use it for and what they expect from the primary transcript. If you have any comments, including whether you think this is appropriate to do at all, please fill in the survey so that we can take them into account.

Please note that we have no intention of stripping down our transcript set to only the "primary". The aim is to keep the full set of transcripts, and keep expanding upon it, but highlight one or more transcripts for those who wish to have that extra annotation.

[r.rosati]

Thank you. I'm very curious to see the result of the survey!

[Emily_Ensembl]

We will close this at midnight (BST) on Thursday. If you wish to have your say, you've got two days to do it.

[Emily_Ensembl]

We've got a blog post coming out about this in the next few days.

[Emily_Ensembl]

Here's the blog post: http://www.ensembl.info/2018/10/12/o...-mane-project/