A platform for replacing genotyping arrays with sequencing

Joe Pickrell
May 19, 2018 · 3 min read

tl;dr: Gencove has opened up a platform for low-pass sequencing, available at gencove.com

About ten months ago, I discussed the arguments for using low-pass sequencing as a replacement for genotyping arrays. The key argument is that sequencing-based technologies (when combined with advances in imputation algorithms) allow one to collect more data at a lower cost than genotyping technologies.

Since I wrote that blog post, sequencing costs have continued to decline, our molecular biology processes have become more efficient, and our imputation algorithms have continued to improve. Indeed, we have been offering low-pass sequencing as a service to leading academic, biotech, and pharma research groups. Today, I’m pleased to announce that we are making this technology broadly available as a platform for scientists in these sectors.

This platform consists of three products — the first two are low-pass sequencing along with imputation at different levels of sequencing coverage. We calibrated these coverages to allow for imputation that outperforms genotyping arrays of comparable prices: 0.4X coverage outperforms the Illumina Global Screening Array and similar arrays across populations, while 1X coverage additionally outperforms the Affymetrix Biobanking Array. Since these are sequencing-based assays, at large sample numbers, both can be used to identify new genetic variants that have previously never been observed.

Image for post
Image for post
Imputation quality from Gencove sequencing platforms and array platforms in European and African populations

The third product additionally includes custom content — we’ve designed a sequence capture assay that allows for the capture of a set of regions (for example, exons from a set of important genes, or a set of known SNPs of interest) in addition to low-pass sequencing from the rest of the genome, while retaining cost-effectiveness. In research applications, this effectively allows a scientist to place a prior on what parts of the genome they expect to be important for their trait of interest.

As an example application of the capture assay, you might imagine research on cardiovascular disease risk: we know that there are many thousands of genetic variants with small effects on heart disease risk that are spread across the genome, along with a few variants of larger effect in genes like LDLR. Commonly-used gene panels are unable to measure the polygenic component of risk, while genotyping arrays do not comprehensively assay the genes of large effect. A low-pass sequencing plus capture assay measures both aspects of risk in a scalable and cost-effective manner.

How is this platform being used? A few examples of collaborations we’re working on are:

  • The Panel Study of Income Dynamics at the University of Michigan is the longest running longitudinal household survey in the world. To study the influences of genetic and environmental factors on their participants, we’re using low-pass sequencing to perform genome-wide association studies and calculate polygenic risk scores for different traits and diseases.
  • The Systems Genomics Lab at the Baker Institute is developing a polygenic risk score to identify individuals at risk of celiac disease. To develop both build and validate this score, they are sequencing a large cohort of Australian celiac disease patients (and controls) with Gencove.
  • The Darwin’s Dogs Project from the Broad Institute and University of Massachusetts Medical School is a crowdsourced research project on the genetics of dog behavior. We’re working with them to develop improved ancestry/breed analyses and imputation algorithms for canine applications.

We’re always excited to hear about new ideas for how to apply low-pass sequencing technology — contact us at support@gencove.com and let us know what you’re working on!

Behind the scenes at Gencove

Medium is an open platform where 170 million readers come to find insightful and dynamic thinking. Here, expert and undiscovered voices alike dive into the heart of any topic and bring new ideas to the surface. Learn more

Follow the writers, publications, and topics that matter to you, and you’ll see them on your homepage and in your inbox. Explore

If you have a story to tell, knowledge to share, or a perspective to offer — welcome home. It’s easy and free to post your thinking on any topic. Write on Medium

A button that says 'Download on the App Store', and if clicked it will lead you to the iOS App store
A button that says 'Get it on, Google Play', and if clicked it will lead you to the Google Play store