Provide reference files for WES for ASCAT

[maxulysse]

Issue by @anuragksingh, moved from SciLifeLab#763

Hello,
I had some doubts over ascat.
It would be really helpful if you can provide some insights about that.

Can we use the available ascat directly on WES data?
I guess the creation of BAF and LogR files from bam would be same for WES data also.
Or do we need to apply additional filters to use ascat on WES data?
For reference kindly see this link:
VanLoo-lab/ascat#19
Also does we need to add --exome flag when running ascat on WES data?

Any suggestions on above aspects would be really helpful.

Thanks

Comments:

@maxulysse

Running ASCAT for WES is definitively something that we're thinking about.
I remember reading about this link before, I'll definitively look more into it.
Thanks again for all your interest in this project

@szilvajuhos

To run ASCAT on exome you will need a separate file of SNPs that is covering the targeted exons only

@dingxm

Hi,
We are trying to analyze exome data for copy number.
The exome data has extended probes covering regions outside of the exomes.
It seems that last year ASCAT could not use exome data without pre-processing, is this still true or is there a version that deals with Exome data now?
Thank you

@szilvajuhos

Hej,
If you have a BED file that is covering your WES target, I would recommend to make a .loci file i.e. by filtering the latest dbSNP for common biallelic SNPs that are overlapping your target.
You have to have quite a few loci positions (since the target is smaller and the genome is not covered evenly) to make sure you will still have enough SNPs.
@malinlarsson is better in playing with it, the .loci file I have created contains ~16M lines:

$ wc -l dbSNP_151_S04380110_AllExonV5_hg38.loci
16200625
$ head -3 dbSNP_151_S04380110_AllExonV5_hg38.loci
chr1    65529
chr1    65552
chr1    65591

We have managed to make meaningful charts with this loci file (I can share it if you want to give a try), but certainly it is only the beginning of finding the right settings.

[SusiJo]

Hi,
this might be also of interest: The developers of Ascat recommend to use the Battenberg reference files for WES and explain how they can be created see here.

[FriederikeHanssen]

So this issue is halfway addressed (see #606 ). It is possible now to use ASCAT with WES, however, we are currently not providing the necessary reference files:

Reanme: Provide ASCAT WES reference files for GATK.GRCh38

[FriederikeHanssen]

Will move this to backlog, we can provide the references in 3.1