Assign translational effect to custom variant_class values

[u9090]

Hi,

It seems that only 'Silent' mutations are assigned a 'Synonymous' translational effect on the mutation burden plot.

Is there a way to assign translational effects on a custom list of variant class?

For example to also assign 'Intron', 'UTR' and 'Flanking regions' a synonymous effect.

[zlskidmore]

Unfortunately not at this time, I do plan to add the option of coloring bars in the subplots by mutation type but that functionality is not ready yet. leaving this open as an enhancement

[u9090]

Sorry, but it seems to me that counting a mutation occurring in an intron, UTR, flanking or intergenic region (i.e. non-coding regions) as non-synonymous (i.e. ending up in a protein sequence change) is wrong. It is not an enhancement.

[zlskidmore]

@lavv2 sorry, I was only thinking in terms of linking the existing issue which is currently classified as an enhancement, however, I of course agree with you, adding bug label instead. Do you have any thoughts on the proper way to go about this? There is no way to know the effect an intron will have without additional information, for example an intronic mutation could cause a some type of splice effect altering the protein in which case it should be non-synonymous or it could not and as you say should be classified as synonymous.

I think the way to go about this is to remove the synonymous/nonsynonymous classification and add a parameter to either just do a regular barplot, or alternatively a stacked barplot based on the variant_class. Do you agree?

[u9090]

Thanks for considering this issue.

Not sure a stacked barplot based on the 'variant_class' would add more useful information than what is already in the main plot. The added value of the Translational Effect info is the concise and larger clustering of variant types I guess.

The issue may come from the format of the custom file type input. I personally use Annovar which defines slightly different variant classes compared to MAF or MGI format (see the 2 tables here: http://annovar.openbioinformatics.org/en/latest/user-guide/gene/#output-file-1-refseq-gene-annotation). For splicing, if the mutation is within 2-bp (default) to a splice site, it is assumed that it will have a non-synonymous effect as you mentioned. But this region length could be different for other user purposes.

From your side I am not sure you can do much to predict user annotation format. To my perspective (and not to make yourself crazy) the best way would be to let the user deal with what is synonymous and not.

[zlskidmore]

that makes sense, I am adding support for additional filetypes, I will add annovar to the list. But I will add in the functionality to let a user decide what is synonymous while i'm at it if filetype is custom

[zlskidmore]

Work for this is being done here https://github.com/griffithlab/GenVisR/tree/S4_conversion

[zlskidmore]

fixed in 72d045fcb86c57b08180ac1fbd0c2b0833e0cd01

[snashraf]

I have used VCF2MAF for converting my VCF to MAF file and then I am trying to use GenVisR for plotting and its WGS data from Non-Cancer sample but wanted to plot waterfall plots for few ganes. Is their a way to drop all non supporting annotation from genVisR ? Detected an invalid mutation type, valid values for maf are: Nonsense_Mutation, Frame_Shift_Ins, Frame_Shift_Del, Translation_Start_Site, Splice_Site, Nonstop_Mutation, In_Frame_Ins, In_Frame_Del, Missense_Mutation, 5'Flank, 3'Flank, 5'UTR, 3'UTR, RNA, Intron, IGR, Silent, Targeted_Region, NA

[zlskidmore]

I would recommend setting fileType="Custom" and using variant_class_order to set valid annotations. It will automatically fail if all the annotation types are not set but otherwise it should be fine.

Let me know if that works for you

[snashraf]

Is their a way to ignore all which is not mentioned in variant_class_order rather than just failing it ?

On Thu, Jan 25, 2018 at 6:48 PM, Zachary Skidmore notifications@github.com wrote:

I would recommend setting fileType="Custom" and using variant_class_order to set valid annotations. It will automatically fail if all the annotation types are not set but otherwise it should be fine.

Let me know if that works for you

— You are receiving this because you commented. Reply to this email directly, view it on GitHub https://github.com/griffithlab/GenVisR/issues/296#issuecomment-360507342, or mute the thread https://github.com/notifications/unsubscribe-auth/AEJUN-49rmlsNmckqxC9Xfxq5Ny12JaHks5tOKJrgaJpZM4MaDHy .

-- Syed Najeeb Ashraf

[snashraf]

OK Thanks !! I did it by filtering the datasets only !! Thanks

On Thu, Jan 25, 2018 at 9:18 PM, Syed Najeeb Ashraf < syednajeebashraf@gmail.com> wrote:

Is their a way a ignore all which is not mentioned in variant_class_order rather tha just failing it ?

On Thu, Jan 25, 2018 at 6:48 PM, Zachary Skidmore < notifications@github.com> wrote:

I would recommend setting fileType="Custom" and using variant_class_order to set valid annotations. It will automatically fail if all the annotation types are not set but otherwise it should be fine.

Let me know if that works for you

— You are receiving this because you commented. Reply to this email directly, view it on GitHub https://github.com/griffithlab/GenVisR/issues/296#issuecomment-360507342, or mute the thread https://github.com/notifications/unsubscribe-auth/AEJUN-49rmlsNmckqxC9Xfxq5Ny12JaHks5tOKJrgaJpZM4MaDHy .

-- Syed Najeeb Ashraf

-- Syed Najeeb Ashraf