One frequent question we hear on Genohub is, ‘should I make a custom panel for this gene set, or not bother and do whole exome sequencing?’. While whole genome sequencing approaches can capture all possible mutations, whole exome or targeted gene panel sequencing are cost-effective approaches for capturing phenotype altering mutations. We go into the advantages of WGS vs. WES in an earlier blog post. A remaining question however is, among targeting approaches, which is best. We attempt to address this here:

Advantages of targeting all exons – whole exome sequencing (WES)

If your study is discovery based, in other words you don’t know what genes you need to target, WES is the obvious choice.

• Better for discovery based applications where you’re not sure what genes you should be targeting.
• Exome panels are commercially available, they don’t need to be customized or designed.
• Exome sequencing services are fairly standard, costs range between $550-800 for 100-150x mean on target coverage.

Advantages of targeted gene panels (amplicon-seq or targeted hybridization methods)

Targeted gene panels are ideal for analyzing specific mutations or genes that have suspected associations with disease.

• Focusing on individual genes or gene regions allows you to sequence at a much higher depth than exome-seq, e.g. 2,000-10,000x as opposed to 200x which is typical with exome-seq.
• High depth sequencing enables the identification of rare variants
• Can be customized for different samples types, e.g. FFPE, cf/ctDNA, degraded samples.
• Lower input amounts can be used with targeted gene panels (1 ng vs. 100 ng with whole exome sequencing).
• Gene panels can be customized to only include genomic regions of interest. Why sequence everything when you don’t need that extra information?
• Panels can be easily designed for non-human species. Designing a non-human exome is much more laborious.
• Gene panel workflows are a lot simpler and time to results is often as little as 1-2 days.
• You can process thousands of samples on a single sequencing run. Targeted gene panels can be run at a higher throughput and are often more cost-effective than whole exome sequencing.

By focusing on genes likely to be involved with disease, you can reduce expense and focus sequencing resources on your targeted region. However, if you only have a few samples that you need to sequence at a low depth of coverage, consider whether it’s worth designing a panel vs. performing whole exome sequencing using an existing commercial panel.

If you’re interested in designing a custom gene panel or already have an existing panel you’d like to sequence, submit a request describing your project or view several of the existing commercially available panels here.