Linking genome variation with haplotype-resolved sequencing

Introduction

DNA sequencing has transformed biological research and is fast becoming the standard-of-care in medicine. Chances are good that every European person born today may have their genome sequenced at some point in their lifetime (it is already happening in Iceland).

Current Sequencing Platforms

The currently prevailing sequencing platform, Illumina short-read sequencing, prioritizes content (DNA base pairs) over preserving long-range haplotype context. This decision has paid off so far, but comes at the cost of complicated analyses and often leads to undetected disease-causing chromosome rearrangements.

Alternative Technologies

Alternative “long-read” technologies, however, have yet to deliver the scale and throughput to truly take over from Illumina sequencing. To meet the grand challenge of sequencing humanity and biodiversity, we need both content and context.

Haplotagging Technique

As part of our ERC StG action, we have invented haplotagging, a technique that restores haplotype context while integrating seamlessly into Illumina sequencing. We have previously published a small-scale pilot study that demonstrates haplotagging can deliver superior results at a fraction of existing costs.

Challenges Overcome

In doing so, our team has solved a series of molecular engineering and computational challenges that have stumped far larger parties. However, our prototype dataset is still not large enough to fully allay concerns from potential licensees regarding robust scalability.

Proposal for Mid-Scale Pilot

Thus, we propose to generate a mid-scale, 2000-sample pilot with direct support from Illumina to provide additional benchmark data, guide scale-up efforts, and inform decision-making by industry and academic stakeholders.

Expected Outcomes

We expect this proposal will help transition haplotagging from a research concept towards the market.