Linking genome variation with haplotype-resolved sequencing

Project Information

HAPLOTAGGING

Grant agreement ID: 101069216

DOI

10.3030/101069216

Project closed

EC signature date 28 April 2022

Start date 1 May 2022

End date 31 October 2023

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany

Periodic Reporting for period 1 - HAPLOTAGGING (Linking genome variation with haplotype-resolved sequencing)

Reporting period: 2022-05-01 to 2023-10-31

Summary of the context and overall objectives of the project

Just like blood tests and X-rays screens, getting one’s genome screened is an increasingly important component to healthcare. Our genome carries information about a person’s risks to diseases, as well as her family’s history. Getting this right will be key to healthy ageing and personalised medicine. In this project, we apply a novel technique called haplotagging that delivers high-quality genomes at a fraction of current costs to deliver human genomes. Haplotagging is among a new class of genome sequencing techniques that extends the industry-standard “short-read” sequencing by supplying the “context”. This technique will allow us to get a more complete profile of a participant’s genome better and faster for large-scale studies. By sequencing 2000 human genomes in this project using haplotagging, it allows us to demonstrate the scalability and readiness of haplotagging for surveying large populations. The results from this POC project have attracted industry funding and have enabled further up-take of this technique in additional national biobank projects.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

As part of this POC action, 2000 human genomes from across the world have been generated using a newly developed, advanced form of sequencing called haplotagging. Unlike traditional genome sequencing, haplotagging captures and preserves the chromosomal context to allow superior reconstruction of a person’s genomic make-up. This POC action builds on previous work from the haplotagging team that described 105 British samples, and now takes the pilot data to the next level. It also allows testing and improvement of the technique, which has led to a wave of interested parties and partners from academic researchers and industry partners alike. We have also managed to use this data to build “chromosome-level” assemblies from scratch, reaching a scaffold N50 of 35.2 Mbp and a phaseblock N50 of over 10 Mbp.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Our platform and results from haplotagging have performed impressively through TLRs1 - 4. For haplotagging to achieve further success in transition towards the market, it will need a stable structure, further demonstration, and access to financing. During the last part of the funding period, the PI has accepted a permanent position away from the Hosting Institution. The move of the PI has taken up much time and logistical effort that have also impacted the progress of this Action. In the last few months, the PI has struck new collaboration agreements with local and other European (and UK) researchers to launch new projects and to obtain financing. In that sense, we have achieved a level on par with the state-of-the-art. Through extensive discussions with commercial and academic partners, we are confident that we have a “working product” as such. We will now intensify the effort to establish a spin-out.

Across the various areas, we assess our progress as follows:
Further research: we have an existing “working product” as such. Therefore further research is needed to develop further improvements, rather than needing to establish proof-of-concept as such.
Demonstration: we have demonstrated the basic principles and scalability at a mid-level. Real-life commercial projects often involve samples in the range of 100 - 1000 samples. These we can handle on a regular basis. For larger projects such as the Lifelines biobank (167000 samples), we have sufficiently demonstrated capabilities so far, but will need to grow further to be able to undertake such demonstrations. For that purpose, further funding would be very beneficial.
Access to markets and finance: access to markets at a small scale is already achieved. However, financing and a defined spin-out structure is currently the largest challenge. We have not founded a spin-off as such. The focus will be on getting this established, in order to access financing and funds that will enable such work.
Commercialisation: we have not attempted this aspect yet.
IPR support: we have been provided with professional support from within the Host Institution in the form of Max Planck Innovations, the Technology Transfer office. We are in a good position to undertake further such work.

A composite image of the haplotagging bead and a representation of chromosomes built from sequences