The Good, the Bad and the Expensive of Whole Genome Sequencing

Whole Genome Sequencing (WGS) is still very cutting edge, sequencing technology and while there are a lot of perks to using it, there are also a few drawbacks. The good, the bad and the pricey are outlined below to help you navigate when it’s worth using WGS!

Whole Genome Sequencing: The Good

Lots of Data

WGS is the best way to get a lot of data all at once. No other sequencing method allows you to get data for the whole genome of your sample. Because of this, you get hundreds of thousands of base pairs to sort though to your hearts content. Think of it as no stone left unturned. If it’s in your sequence, you will see it!

High Resolution Results

WGS provides high resolution results which allow you to identify small (and large) variants because you can see every single base laid out in front of you. You can identify single mutations, even insertions and deletions using WGS. These are often referred to as SNPs or single nucleotide polymorphisms. This technique is powerful because you can compare your sequence to a reference and easily identify SNPs, or other interesting features of your sequence. WGS has been used to identify many SNPs in the human genome that are potentially linked to illnesses like breast cancer or heart disease.

Fast-Relatively Speaking

A large sequence still takes time, but it is faster and less confounding than other sequencing methods in which you have to sequence little pieces at a time and then try to piece them together!

Whole Genome Sequencing: The Bad

Lots of Data

More data isn’t always a good thing. Even though WGS gives you a plethora of information, you need to dedicate time to annotate and analyze your results. You often need a person just dedicated to interpreting sequencing data.

“You Must Construct Additional Pylons” Aka-More Power!

Not just electricity, you need a powerful computer to generate your data in a reasonable time. You can’t just hook up you laptop and expect a sequence to come out in a couple hours. Even the most powerful computers still take hours or even days to fully sequence genomes, depending on size and complexity. Because of this, many labs outsource sequencing to companies or special labs since it’s cost prohibitive to set up in their own facility.

Open Your Wallet

Obviously, having to dedicate more time and more power to sequence a genome hikes up the costs to make it happen. This is the biggest barrier to labs who want to use this technique. The upfront costs often prohibit labs from using the technique or force them to be very choosy over which samples are sent for sequencing. Again, most labs pay an outside company to do this for them as its cheaper than setting up the facility in house. In addition, the larger the genome you are sequencing, the more expensive it is to run.

Can I Get a Reference?

Perhaps one of the biggest drawbacks is the need for a reference genome for comparison with your sequence. If you don’t have one of these to compare your results to, you have no real way of determining what is normal and what is unique about your sample. Good luck identifying an insertion mutation without an unaltered genome to compare to! While de novo sequencing for when a reference is not available is possible, it can lead to more errors since you have nothing to compare to.

While there are a lot of drawbacks to WGS, the advantages are hard to beat. No other method achieves such high resolution data for your sequence of interest. When you need high resolution data or need to identify small discrepancies in your sequence, WGS is the way to go!

Have you used WGS or would you be interested in using it for you lab applications? Comment below!

Further Reading

1. Schneeberger. (2014) Using next-generation sequencing to isolate mutant genes from forward genetic screens. Nature Reviews Genetics. 15:662–76. Figure 3.
2. Ng P.C., Kirkness E.F. (2010) Whole Genome Sequencing. In: Barnes M., Breen G. (eds) Genetic Variation. Methods in Molecular Biology (Methods and Protocols), vol 628. Humana Press, Totowa, NJ
3. Illumina. Introduction to Whole-Genome Sequencing.