Assigning parent features to transcripts

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Assigning parent features to transcripts

Faye Rodgers

Hi Nathan et al,

 

I have a question about how Apollo decides whether two annotated transcripts derive from the same parent gene. As far as I can tell, it seems that transcripts are considered to derive from the same parent only if they share CDS, is that correct?

 

Secondly, is it possible to override this behaviour? For example, if we wanted to force-assign a new transcript to share a parent with an existing transcript with whom it shared UTR but not CDS?

 

Best wishes,

Faye

-- The Wellcome Trust Sanger Institute is operated by Genome Research Limited, a charity registered in England with number 1021457 and a company registered in England with number 2742969, whose registered office is 215 Euston Road, London, NW1 2BE.



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Re: Assigning parent features to transcripts

nathandunn


On Nov 23, 2017, at 6:18 AM, Faye Rodgers <[hidden email]> wrote:

Hi Nathan et al,
 
I have a question about how Apollo decides whether two annotated transcripts derive from the same parent gene. As far as I can tell, it seems that transcripts are considered to derive from the same parent only if they share CDS, is that correct? 

Yes.

Secondly, is it possible to override this behaviour? For example, if we wanted to force-assign a new transcript to share a parent with an existing transcript with whom it shared UTR but not CDS?

You could add a feature to do this to Apollo.  Please add an issue here with details:


If you have dev time on your side, we’d be happy to point you in the right direction, as well.

Nathan

 
Best wishes,
Faye
-- The Wellcome Trust Sanger Institute is operated by Genome Research Limited, a charity registered in England with number 1021457 and a company registered in England with number 2742969, whose registered office is 215 Euston Road, London, NW1 2BE. 


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Re: Assigning parent features to transcripts

Suzanna Lewis-3
In reply to this post by Faye Rodgers
Regarding your first question. Not only must the CDS overlap, but they need to be in the same reading frame. In other words. that the resulting proteins from each transcript would generate some shared aa sequence.

Regarding the second, I wasn't going to say anything, but now I'm curious. Why would you want to do this, what biological phenomenon behaves like this? Is it a dicistronic transcript? Or is there a problem with the assembly? I'd just like to better understand the circumstances because I'm very hesitant to introduce anything that isn't based on accurate biology. That could lead us into all tons of trouble in the future. Would you describe the circumstances?



On Thu, Nov 23, 2017 at 2:18 PM, Faye Rodgers <[hidden email]> wrote:

Hi Nathan et al,

 

I have a question about how Apollo decides whether two annotated transcripts derive from the same parent gene. As far as I can tell, it seems that transcripts are considered to derive from the same parent only if they share CDS, is that correct?

 

Secondly, is it possible to override this behaviour? For example, if we wanted to force-assign a new transcript to share a parent with an existing transcript with whom it shared UTR but not CDS?

 

Best wishes,

Faye

-- The Wellcome Trust Sanger Institute is operated by Genome Research Limited, a charity registered in England with number 1021457 and a company registered in England with number 2742969, whose registered office is 215 Euston Road, London, NW1 2BE.




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Re: Assigning parent features to transcripts

Kevin Howe

Hi Suzi, 

There are over 100 genes in the human GENCODE set that have a transcript with a CDS that has no genomic overlap with the CDSs of the other transcripts in the gene. They've sometimes been been grouped together into a single gene because they share exon space in some way (sometimes even sharing the first exon); and sometimes because a HAVANA curator chose to represent the locus that way. 

And it turns out that this restriction in Apollo is more extensive than non-overlapping CDSs. As it stands, Apollo will not let us add any non-coding transcripts (i.e. transcripts without a CDS) to an existing protein-coding gene. It seems that it will always create a distinct gene for *any* non-coding transcript. This makes it very difficult to use for human and model organisms where genes often comprise of many transcripts having a variety of biotypes (pseudogenic, NMD, etc etc). I'm kind of surprised that this issue has never been reported before. It makes me wonder whether we are missing a menu option somewhere....

Regarding the (non)overlapping CDSs though, I think what Apollo is doing is a completely reasonable default behaviour, but (in our opinion) there should be a way for a curator to override this and link transcripts together into genes in whichever way they like. Principle of Curator-Knows-Best.

Best,

Kevin


On 27 November 2017 at 15:15, Suzanna Lewis <[hidden email]> wrote:
Regarding your first question. Not only must the CDS overlap, but they need to be in the same reading frame. In other words. that the resulting proteins from each transcript would generate some shared aa sequence.

Regarding the second, I wasn't going to say anything, but now I'm curious. Why would you want to do this, what biological phenomenon behaves like this? Is it a dicistronic transcript? Or is there a problem with the assembly? I'd just like to better understand the circumstances because I'm very hesitant to introduce anything that isn't based on accurate biology. That could lead us into all tons of trouble in the future. Would you describe the circumstances?



On Thu, Nov 23, 2017 at 2:18 PM, Faye Rodgers <[hidden email]> wrote:

Hi Nathan et al,

 

I have a question about how Apollo decides whether two annotated transcripts derive from the same parent gene. As far as I can tell, it seems that transcripts are considered to derive from the same parent only if they share CDS, is that correct?

 

Secondly, is it possible to override this behaviour? For example, if we wanted to force-assign a new transcript to share a parent with an existing transcript with whom it shared UTR but not CDS?

 

Best wishes,

Faye

-- The Wellcome Trust Sanger Institute is operated by Genome Research Limited, a charity registered in England with number 1021457 and a company registered in England with number 2742969, whose registered office is 215 Euston Road, London, NW1 2BE.




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Re: Assigning parent features to transcripts

Suzanna Lewis-3
Hi Kevin,

Thanks. I remember when we first were doing this (i.e. desktop apollo) we had different definitions of 'gene' according to project. So for fly (the default) it was strictly transcripts with overlapping, in-frame CDS regions defined a protein coding gene. For other projects the definition was simply overlapping transcripts. We had different plug-ins for the different gene rule definitions. Lots of interesting biology, like shared 5' UTR, but completely different set of coding exons that followed led to separate genes; or almost completely different proteins-but one aa in common so a single gene; or overlapping CDSs - but not in the same frame, so different genes. 

If Apollo is more restrictive than non-overlapping, in-frame CDSs, then it's a bug. But I don't think that's quite what you mean. 

For pseudogenes we've always put them in a separate pot from their progenitor gene (especially since they are often very far away). Are you saying there are cases where you want to indicate non-coding transcripts coming off the same promoter? I could see that happening - definitely could use an override there. 

For NMD, there was (and should still be) a means for the curator to indicate that the stop codon is going to be a read-through. If that has been lost along the way, then it needs to be restored. That way you can obtain the resulting protein as well.

There was also a means of indicating translational frame shifts (+/-1) which is also a genuine biological occurrence we need to account for. Nathan is that still enabled?

Experienced curators always knows best, just want to be sure it's tracked and recorded to explain it to downstream consumers, and also make sure it's the root issue and not a work around for something like NMD.

Be good to chat to work out all the fiddly bits. 

Also will be in your neighborhood again in January. I'd love to come by and work with you on this if possible (Jan 17-19 open).

-S




On Mon, Nov 27, 2017 at 5:08 PM, Kevin Howe <[hidden email]> wrote:

Hi Suzi, 

There are over 100 genes in the human GENCODE set that have a transcript with a CDS that has no genomic overlap with the CDSs of the other transcripts in the gene. They've sometimes been been grouped together into a single gene because they share exon space in some way (sometimes even sharing the first exon); and sometimes because a HAVANA curator chose to represent the locus that way. 

And it turns out that this restriction in Apollo is more extensive than non-overlapping CDSs. As it stands, Apollo will not let us add any non-coding transcripts (i.e. transcripts without a CDS) to an existing protein-coding gene. It seems that it will always create a distinct gene for *any* non-coding transcript. This makes it very difficult to use for human and model organisms where genes often comprise of many transcripts having a variety of biotypes (pseudogenic, NMD, etc etc). I'm kind of surprised that this issue has never been reported before. It makes me wonder whether we are missing a menu option somewhere....

Regarding the (non)overlapping CDSs though, I think what Apollo is doing is a completely reasonable default behaviour, but (in our opinion) there should be a way for a curator to override this and link transcripts together into genes in whichever way they like. Principle of Curator-Knows-Best.

Best,

Kevin


On 27 November 2017 at 15:15, Suzanna Lewis <[hidden email]> wrote:
Regarding your first question. Not only must the CDS overlap, but they need to be in the same reading frame. In other words. that the resulting proteins from each transcript would generate some shared aa sequence.

Regarding the second, I wasn't going to say anything, but now I'm curious. Why would you want to do this, what biological phenomenon behaves like this? Is it a dicistronic transcript? Or is there a problem with the assembly? I'd just like to better understand the circumstances because I'm very hesitant to introduce anything that isn't based on accurate biology. That could lead us into all tons of trouble in the future. Would you describe the circumstances?



On Thu, Nov 23, 2017 at 2:18 PM, Faye Rodgers <[hidden email]> wrote:

Hi Nathan et al,

 

I have a question about how Apollo decides whether two annotated transcripts derive from the same parent gene. As far as I can tell, it seems that transcripts are considered to derive from the same parent only if they share CDS, is that correct?

 

Secondly, is it possible to override this behaviour? For example, if we wanted to force-assign a new transcript to share a parent with an existing transcript with whom it shared UTR but not CDS?

 

Best wishes,

Faye

-- The Wellcome Trust Sanger Institute is operated by Genome Research Limited, a charity registered in England with number 1021457 and a company registered in England with number 2742969, whose registered office is 215 Euston Road, London, NW1 2BE.




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Re: Assigning parent features to transcripts

nathandunn

We still allow users to indicate stop codon read-throughs, but we currently have no way of indicating translational frame-shifts at present. 

While we can certainly allow manual assignment, our preference is to allow the underlying biology to automatically determine this. 

We can setup a meeting off-line to determine all of the biological use-cases directly.   


Nathan

On Nov 27, 2017, at 10:02 AM, Suzanna Lewis <[hidden email]> wrote:

Hi Kevin,

Thanks. I remember when we first were doing this (i.e. desktop apollo) we had different definitions of 'gene' according to project. So for fly (the default) it was strictly transcripts with overlapping, in-frame CDS regions defined a protein coding gene. For other projects the definition was simply overlapping transcripts. We had different plug-ins for the different gene rule definitions. Lots of interesting biology, like shared 5' UTR, but completely different set of coding exons that followed led to separate genes; or almost completely different proteins-but one aa in common so a single gene; or overlapping CDSs - but not in the same frame, so different genes. 

If Apollo is more restrictive than non-overlapping, in-frame CDSs, then it's a bug. But I don't think that's quite what you mean. 

For pseudogenes we've always put them in a separate pot from their progenitor gene (especially since they are often very far away). Are you saying there are cases where you want to indicate non-coding transcripts coming off the same promoter? I could see that happening - definitely could use an override there. 

For NMD, there was (and should still be) a means for the curator to indicate that the stop codon is going to be a read-through. If that has been lost along the way, then it needs to be restored. That way you can obtain the resulting protein as well.

There was also a means of indicating translational frame shifts (+/-1) which is also a genuine biological occurrence we need to account for. Nathan is that still enabled?

Experienced curators always knows best, just want to be sure it's tracked and recorded to explain it to downstream consumers, and also make sure it's the root issue and not a work around for something like NMD.

Be good to chat to work out all the fiddly bits. 

Also will be in your neighborhood again in January. I'd love to come by and work with you on this if possible (Jan 17-19 open).

-S




On Mon, Nov 27, 2017 at 5:08 PM, Kevin Howe <[hidden email]> wrote:

Hi Suzi, 

There are over 100 genes in the human GENCODE set that have a transcript with a CDS that has no genomic overlap with the CDSs of the other transcripts in the gene. They've sometimes been been grouped together into a single gene because they share exon space in some way (sometimes even sharing the first exon); and sometimes because a HAVANA curator chose to represent the locus that way. 

And it turns out that this restriction in Apollo is more extensive than non-overlapping CDSs. As it stands, Apollo will not let us add any non-coding transcripts (i.e. transcripts without a CDS) to an existing protein-coding gene. It seems that it will always create a distinct gene for *any* non-coding transcript. This makes it very difficult to use for human and model organisms where genes often comprise of many transcripts having a variety of biotypes (pseudogenic, NMD, etc etc). I'm kind of surprised that this issue has never been reported before. It makes me wonder whether we are missing a menu option somewhere....

Regarding the (non)overlapping CDSs though, I think what Apollo is doing is a completely reasonable default behaviour, but (in our opinion) there should be a way for a curator to override this and link transcripts together into genes in whichever way they like. Principle of Curator-Knows-Best.

Best,

Kevin


On 27 November 2017 at 15:15, Suzanna Lewis <[hidden email]> wrote:
Regarding your first question. Not only must the CDS overlap, but they need to be in the same reading frame. In other words. that the resulting proteins from each transcript would generate some shared aa sequence.

Regarding the second, I wasn't going to say anything, but now I'm curious. Why would you want to do this, what biological phenomenon behaves like this? Is it a dicistronic transcript? Or is there a problem with the assembly? I'd just like to better understand the circumstances because I'm very hesitant to introduce anything that isn't based on accurate biology. That could lead us into all tons of trouble in the future. Would you describe the circumstances?



On Thu, Nov 23, 2017 at 2:18 PM, Faye Rodgers <[hidden email]> wrote:

Hi Nathan et al,

 

I have a question about how Apollo decides whether two annotated transcripts derive from the same parent gene. As far as I can tell, it seems that transcripts are considered to derive from the same parent only if they share CDS, is that correct?

 

Secondly, is it possible to override this behaviour? For example, if we wanted to force-assign a new transcript to share a parent with an existing transcript with whom it shared UTR but not CDS?

 

Best wishes,

Faye

-- The Wellcome Trust Sanger Institute is operated by Genome Research Limited, a charity registered in England with number 1021457 and a company registered in England with number 2742969, whose registered office is 215 Euston Road, London, NW1 2BE.




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Re: Assigning parent features to transcripts

nathandunn

For anyone interested, the follow-up is here:


We are going to provide a global option to do gene associations based on exon overlap instead of CDS overlap, though CDS overlap will still be the default.

We will also users to association transcripts with an existing gene or a novel gene after the manual annotation has been created. 

Nathan


On Nov 27, 2017, at 12:00 PM, Nathan Dunn <[hidden email]> wrote:


We still allow users to indicate stop codon read-throughs, but we currently have no way of indicating translational frame-shifts at present. 

While we can certainly allow manual assignment, our preference is to allow the underlying biology to automatically determine this. 

We can setup a meeting off-line to determine all of the biological use-cases directly.   


Nathan

On Nov 27, 2017, at 10:02 AM, Suzanna Lewis <[hidden email]> wrote:

Hi Kevin,

Thanks. I remember when we first were doing this (i.e. desktop apollo) we had different definitions of 'gene' according to project. So for fly (the default) it was strictly transcripts with overlapping, in-frame CDS regions defined a protein coding gene. For other projects the definition was simply overlapping transcripts. We had different plug-ins for the different gene rule definitions. Lots of interesting biology, like shared 5' UTR, but completely different set of coding exons that followed led to separate genes; or almost completely different proteins-but one aa in common so a single gene; or overlapping CDSs - but not in the same frame, so different genes. 

If Apollo is more restrictive than non-overlapping, in-frame CDSs, then it's a bug. But I don't think that's quite what you mean. 

For pseudogenes we've always put them in a separate pot from their progenitor gene (especially since they are often very far away). Are you saying there are cases where you want to indicate non-coding transcripts coming off the same promoter? I could see that happening - definitely could use an override there. 

For NMD, there was (and should still be) a means for the curator to indicate that the stop codon is going to be a read-through. If that has been lost along the way, then it needs to be restored. That way you can obtain the resulting protein as well.

There was also a means of indicating translational frame shifts (+/-1) which is also a genuine biological occurrence we need to account for. Nathan is that still enabled?

Experienced curators always knows best, just want to be sure it's tracked and recorded to explain it to downstream consumers, and also make sure it's the root issue and not a work around for something like NMD.

Be good to chat to work out all the fiddly bits. 

Also will be in your neighborhood again in January. I'd love to come by and work with you on this if possible (Jan 17-19 open).

-S




On Mon, Nov 27, 2017 at 5:08 PM, Kevin Howe <[hidden email]> wrote:

Hi Suzi, 

There are over 100 genes in the human GENCODE set that have a transcript with a CDS that has no genomic overlap with the CDSs of the other transcripts in the gene. They've sometimes been been grouped together into a single gene because they share exon space in some way (sometimes even sharing the first exon); and sometimes because a HAVANA curator chose to represent the locus that way. 

And it turns out that this restriction in Apollo is more extensive than non-overlapping CDSs. As it stands, Apollo will not let us add any non-coding transcripts (i.e. transcripts without a CDS) to an existing protein-coding gene. It seems that it will always create a distinct gene for *any* non-coding transcript. This makes it very difficult to use for human and model organisms where genes often comprise of many transcripts having a variety of biotypes (pseudogenic, NMD, etc etc). I'm kind of surprised that this issue has never been reported before. It makes me wonder whether we are missing a menu option somewhere....

Regarding the (non)overlapping CDSs though, I think what Apollo is doing is a completely reasonable default behaviour, but (in our opinion) there should be a way for a curator to override this and link transcripts together into genes in whichever way they like. Principle of Curator-Knows-Best.

Best,

Kevin


On 27 November 2017 at 15:15, Suzanna Lewis <[hidden email]> wrote:
Regarding your first question. Not only must the CDS overlap, but they need to be in the same reading frame. In other words. that the resulting proteins from each transcript would generate some shared aa sequence.

Regarding the second, I wasn't going to say anything, but now I'm curious. Why would you want to do this, what biological phenomenon behaves like this? Is it a dicistronic transcript? Or is there a problem with the assembly? I'd just like to better understand the circumstances because I'm very hesitant to introduce anything that isn't based on accurate biology. That could lead us into all tons of trouble in the future. Would you describe the circumstances?



On Thu, Nov 23, 2017 at 2:18 PM, Faye Rodgers <[hidden email]> wrote:

Hi Nathan et al,

 

I have a question about how Apollo decides whether two annotated transcripts derive from the same parent gene. As far as I can tell, it seems that transcripts are considered to derive from the same parent only if they share CDS, is that correct?

 

Secondly, is it possible to override this behaviour? For example, if we wanted to force-assign a new transcript to share a parent with an existing transcript with whom it shared UTR but not CDS?

 

Best wishes,

Faye

-- The Wellcome Trust Sanger Institute is operated by Genome Research Limited, a charity registered in England with number 1021457 and a company registered in England with number 2742969, whose registered office is 215 Euston Road, London, NW1 2BE.




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