Benefits of Whole genome sequencing over Exome sequencing

[dickie_ho]

Hey everyone.

So what are the benefits from going from WES to WGS ???

Cheers for any help

Josh

[nucacidhunter]

The big gain could be finding portion of missing heritability. Variations in exome explains only a percentage of observed phenotypes and associations.

[dickie_ho]

Thanks nucacidhunter

Finding that missing heritability still remains the key especially in complex disease where the heterogeneity is that large, association is difficult.

I guess the big selling points for me would be the structural variant detection and a better coverage of the exome (hate being limited by the flanking regions).

For future reference if anyone else ever is brainstorming this question (or making the transition) check out the nature paper by Gilissen et al 2014, good example of using WGS compared to WES.

Thanks again nucacidhunter for your input

[dpryan]

It also turns out that WGS is better at calling exome variants than WES is (see here, which was mentioned on the ASHG14 (I think) twitter feed).

[dickie_ho]

Thanks dpryan

This will help build my case for WGS

[lh3]

I guess finding structural variations should be easier with WGS due to even coverage.

[dickie_ho]

Cheers lh3

[ulz_peter]

Just another thought: As sequencing prices drop, target enrichment is a cost-factor. LIbrary preparation for WGS is easier and cheaper than for WES.

[nucacidhunter]

Some benefits of WGS over WES has been discussed in this thread and cited papers. The issue that most researchers are facing is storage, handling and analysis of large data sets. Those that have set up exome analysis pipeline are reluctant to switch to WGS. Sequencing centres that offer WGS along with variant analysis soon should pick up some business in this sector.

[dickie_ho]

Thanks ulz_peter that is also a really good point that i have managed to overlook

My set up at the moment is a 28TB linux box that i build for the purpose of WES and it does the job just fine storing the data when i transfer it back from the cluster.. but preparing for storage for WGS is a bit scary.
We have potential access to a X ten which is why i asked this question....
I am trying to push to do more cases instead of the conventional case/control type of study design and chase down the rare highly penetrate variants and work back to the systems and pathways from there... combined with our RNA-seq and smRNA-seq data being generated on this cohort.. ideas on that approach ??

I do agree with you on the comment about the sequencing centres.. the problem i am starting to see around the place is biologists are given the vcf files and have no clue where to go from that... So if a sequencing centre had like a translational service for biologist i believe it would do really good ...