[miso-users] Events with many gene annotations

[Tyler Funnell]

I would argue that the gene annotations should match the event annotations as closely as possible. If there is a micro RNA in an upstream or downstream intron of a SE event it shouldn't be included because the event is not a skipped exon in the micro RNA. Perhaps someone might be interested in genes in the flanking introns, but including them in the default mapping could be more confusing than helpful.

Cheers,
Tyler

________________________________________
From: Yarden Katz [yardenny at gmail.com] On Behalf Of Yarden Katz [yarden at mit.edu]
Sent: August 28, 2013 3:39 PM
To: Sol Katzman
Cc: Tyler Funnell; miso-users at mit.edu
Subject: Re: [miso-users] Events with many gene annotations

Hi all,

Thanks Sol for sharing your very helpful analysis.  Sol was one of the people to note that the larger events are probably mis-annotated.  These annotations are based on ESTs from work done 2008.

Our revamped annotation set (v2.0 on the website) are generated more conservatively but we do not have yet the AFE/ALE/TandemUTR v2.0 annotations.  Hopefully these will be compiled soon and can be filtered to remove problematic events like these.

Independently of this, I agree that the method Tyler proposed will be more accurate for intersecting events with genes.  In the case of SE however, I'm not sure if it's a feature or a bug to report that a gene that resides in the up or downstream introns of the event is reported as an overlapping gene.

Best, --Yarden



On Aug 28, 2013, at 5:51 PM, Sol Katzman wrote:

> Dear Yarden and Tyler,
>
> A while back, I noticed some performance problems processing AFE/ALE events.
>
> I extracted the distributions of the lengths of the "gene" items in the gff3
> (hg19) event definitions. There are many (1100+/500+) AFE/ALE events over 1Mb in length.
> Only a handful (10) such SE events.
>
> I will send my stats in a follow-up email.
>
> I think that the events longer than 1Mb are pretty questionable.
>
> /Sol.
>
> On 8/28/2013 2:16 PM, Tyler Funnell wrote:
>> Hi Yarden,
>>
>> Yes that's right. The problem is most noticeable for the ALE/AFE events for the reason you mentioned, but I think the current event to gene mapping could have improper annotations for other event types as well. For example, small genes that exist within the introns in a SE event would be picked up.
>>
>> Cheers,
>> Tyler
>>
>>
>> On Aug 28, 2013, at 2:03 PM, Yarden Katz <yarden at mit.edu> wrote:
>>
>>> Hi Tyler,
>>>
>>> Some of the AFE/ALE annotations, which we are currently reworking, have span very large genomic coordinates as you noted.  I believe these are probably dubious/faulty annotations.  But in any case, as you say, if you overlap the outer-most coordinates with genes there will potentially be many overlapping genes.
>>>
>>> If I understand correctly, you're proposing to merge the first exon with all genes, then the second exon will genes, and take the intersection of those?
>>>
>>> Best, --Yarden
>>>
>>> On Aug 27, 2013, at 10:31 PM, Tyler Funnell wrote:
>>>
>>>> Hello,
>>>>
>>>> I've noticed that for some alternative events, there are many gene annotations in the event to ensembl Id mapping file. For example AFE event 83896 at uc002kgt.1@uc002hvt.1 has quite a few. I think this might be because the left-most and right-most coordinates for this particular event cover a large section of the chromosome and the gene mappings are based on these coordinates. If I'm right, I think a better way would be to get the overlap between genes (or gene exons) and individual event exons first, then merge to the event level.
>>>>
>>>> Thank you,
>>>> Tyler
>>>>
>>>>
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>>
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