Ultra High-Throughput Sequencing for Norwich Research Park and the UK National Capability in Genomics
Lead Research Organisation:
Earlham Institute
Department Name: Directorate Office
Abstract
The ability to rapidly and cheaply sequence the genomes of living organisms has revolutionised biological and biomedical research. In the last 10 years the technology to enable this type of research as improved massively, as has our ability to understand the data. Genome sequencing has changed from an activity that required a bespoke factory scale facility to something that requires a single instrument which can be run in university labs across the UK and now even in hand-held devices. However, as the process has become quicker and cheaper, we can now design much larger and more powerful studies and there is still a need for bespoke facilities that can handle the larger study designs that are now possible.
Here we propose to purchase the most recent iteration of short-read sequencing technology, The NovaSeq 6000 and install it at the Earlham Institute, which hosts the BBSRC National Capability in Genomics and Single Cell Analysis. This instrument will enable much more rapid and much cheaper sequencing than was previously possible at EI. The EI is an ideal environment for this instrument as it has access to automation for upstream sample prep. It has a highly trained workforce with a well-established training program and career progression for service delivery staff. EI also has very good IT infrastructure and a team of Bioinformaticians supporting the sequencing lab.
Over a six month period the EI plan to install the platform, benchmark it and make it accessible to the UK bioscience community.
Here we propose to purchase the most recent iteration of short-read sequencing technology, The NovaSeq 6000 and install it at the Earlham Institute, which hosts the BBSRC National Capability in Genomics and Single Cell Analysis. This instrument will enable much more rapid and much cheaper sequencing than was previously possible at EI. The EI is an ideal environment for this instrument as it has access to automation for upstream sample prep. It has a highly trained workforce with a well-established training program and career progression for service delivery staff. EI also has very good IT infrastructure and a team of Bioinformaticians supporting the sequencing lab.
Over a six month period the EI plan to install the platform, benchmark it and make it accessible to the UK bioscience community.
Technical Summary
We propose to purchase an Illumina Novaseq 6000 sequencer to replace the HiSeq 4000 instruments in the Earlham Institute Genomics Pipelines lab which is part of the BBSRC funded National Capability in Genomics. We propose a number of pilot studies (which we will fund) that will enable us to benchmark the performance of the instrument for a number of different study types (including genome re-sequencing, RNAseq and metagenomics). We will then role out this new platform as part of the National Capability in Genomics so that it will be accessible to the entire bioscience community on a competitive fee for service basis. This project has been designed in consultation with a number of other sequencing service labs, and our experience with the platform will be shared.
The NovaSeq has a number of distinct advantages over the current systems. There are a range of different flow-cells that all have greater capacity than the HiSeq 4000s which enable higher throughput and more flexibility in the type of runs that can be performed. The cost per megabase can be up to half the price of current systems and the two-dye coding system enables much faster imaging times. Illumina have stated that this machine architecture will be used to deliver the $100 genome, which means that it will likely be incrementally improved in cost and throughput.
The EI has excellent facilities to house this instrument with automation in place for DNAseq and RNAseq library construction, target capture and low input protocols.
This project will improve delivery of a number of BBSRC projects including the cross institute Designing Future Wheat Institute Strategic Programme. It will also reduce costs for BBSRC researchers accessing the national capability and increase EI capacity to work with industrial partners.
The NovaSeq has a number of distinct advantages over the current systems. There are a range of different flow-cells that all have greater capacity than the HiSeq 4000s which enable higher throughput and more flexibility in the type of runs that can be performed. The cost per megabase can be up to half the price of current systems and the two-dye coding system enables much faster imaging times. Illumina have stated that this machine architecture will be used to deliver the $100 genome, which means that it will likely be incrementally improved in cost and throughput.
The EI has excellent facilities to house this instrument with automation in place for DNAseq and RNAseq library construction, target capture and low input protocols.
This project will improve delivery of a number of BBSRC projects including the cross institute Designing Future Wheat Institute Strategic Programme. It will also reduce costs for BBSRC researchers accessing the national capability and increase EI capacity to work with industrial partners.
Planned Impact
The addition of a new and improved DNA sequencing platform at EI, capable of significantly extends the capabilities of the National Capability in Genomics. This added value, will accelerate genomic research, reap long-term economic benefits and create new commercial opportunities in the UK.
Advanced academic scientific facilities are and important asset for the the UK Bioeconomy and creates new commercial opportunities for research. The proposed capital investment promises to improve cost-effectiveness, efficiency, scalability and benefit all research at the Earlham Institute. EI already collaborates with a number of multinational companies such as Bayer and Unilever but also with local companies on Norwich Research Park such as food forensics. Increased capacity in the genomics pipeline will enable us to do more of this type of consultancy and service work.
To ensure that we disseminate the utility of the new platform we will work with our KEC team to produce publicity and social media interest. We already undertake a many commercial engagement events such as open days to ensure that local and regional businesses are aware of the facilities and capabilities at EI.
Advanced academic scientific facilities are and important asset for the the UK Bioeconomy and creates new commercial opportunities for research. The proposed capital investment promises to improve cost-effectiveness, efficiency, scalability and benefit all research at the Earlham Institute. EI already collaborates with a number of multinational companies such as Bayer and Unilever but also with local companies on Norwich Research Park such as food forensics. Increased capacity in the genomics pipeline will enable us to do more of this type of consultancy and service work.
To ensure that we disseminate the utility of the new platform we will work with our KEC team to produce publicity and social media interest. We already undertake a many commercial engagement events such as open days to ensure that local and regional businesses are aware of the facilities and capabilities at EI.
Organisations
- Earlham Institute (Lead Research Organisation)
- University of Manchester (Collaboration)
- Quadram Institute Bioscience (Collaboration)
- International Rice Research Institute (Collaboration)
- Newcastle University (Collaboration)
- OXFORD NANOPORE TECHNOLOGIES (Collaboration)
- UNIVERSITY OF LIVERPOOL (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- University of East Anglia (Collaboration)
- UNIVERSITY OF EXETER (Collaboration)
Publications
Description | This is an equipment grant: We have baught and installed the machine and run all installation checks We have run all pilot projects that we proposed in the origional award We have set up a cost model for external use and advertised the equipment and have run an early access competition with industry co-funding. We now have numerous lab pipelines for RNA/DNA seq operating on the new equipment. |
Exploitation Route | This equeipment is available to all external users so it cna be used by academia and industry for any research purpose involving DNA sequencing |
Sectors | Agriculture, Food and Drink,Chemicals,Energy,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
URL | http://www.earlham.ac.uk/genomics-services |
Description | We have worked with industry (BASF) to sequence crop genomes. We have also received industry support (from 10 X and Illumina) to run an early access competition. The Novaseq platform is now being used for a fee for service facility by academia and industry. We have case award students using this platform to sequence sugar beet with the BBRO to identify loci important in decease resistance.. |
First Year Of Impact | 2019 |
Sector | Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | Meeting with Trevor Holden Broadland and South Norfolk District Council to discuss place based innovation strategy |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
Description | Membership of BBSRC Transformative technology Panel |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
Impact | The transformative technology strategy advisory panel have influence BBSRC policy on data intensive bioscience and big ideas pipeline |
Description | Darwin Tree of Life |
Amount | £9,360,421 (GBP) |
Funding ID | 218328/Z/19/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2019 |
End | 05/2022 |
Description | Developing a low-cost marker discovery platform to unlock the breeding potential of orphan crops |
Amount | £10,000 (GBP) |
Organisation | Knowledge Transfer Network |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2020 |
End | 08/2020 |
Description | Development of single-cell sequencing technology for microbial populations |
Amount | £149,610 (GBP) |
Funding ID | BB/R022526/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 07/2018 |
End | 06/2019 |
Title | Method for sequencing individual microbial cells and mapping SNP to reference genome data |
Description | We have developed a method for sequencing individual bacterial cells and happy the resulting data to reference genome data to phase SNPs and identify sub populations growing within planktonic cuture. |
Type Of Material | Technology assay or reagent |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | This has been used to identify the impact of low concentration antibiotics on mutation rate. |
URL | https://www.biorxiv.org/content/10.1101/2020.08.25.266213v1 |
Description | EI-QIB collaboration in microbial genomics |
Organisation | Quadram Institute Bioscience |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | There is a joint PDRA post in this area and now a joint PI group. EI is undertaking bioinformatics development and single cell and genomic analysis. We also provide HPC capability. |
Collaborator Contribution | The team at QIB are undertaking the evolutionary experiments, providing samples and data. We work closely with the Webber and Kingsley groups in this area. |
Impact | The collaboration involved microbiology and bioinformatics. |
Start Year | 2015 |
Description | ENQ-3355 |
Organisation | Newcastle University |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Genome data generation to underpin programs in environmental microbiome research. |
Collaborator Contribution | Provision of materials |
Impact | Further understanding of microbiome diversity. |
Start Year | 2018 |
Description | ENQ-3556 |
Organisation | University of Exeter |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Genome data generation to underpin programs in aphid research. |
Collaborator Contribution | Provision of materials |
Impact | Genomic resources to characterise a large number of aphid clones. |
Start Year | 2019 |
Description | ENQ-3628 |
Organisation | University of Liverpool |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Genome data generation to underpin programs in parasite biology. |
Collaborator Contribution | Provision of materials |
Impact | Characterisation of the genomes of parasite organisms. |
Start Year | 2019 |
Description | ENQ-3859 |
Organisation | International Rice Research Institute |
Country | Philippines |
Sector | Charity/Non Profit |
PI Contribution | Genome data generation of rice samples. |
Collaborator Contribution | Provision of materials |
Impact | Genomic resources to better understand variation in rice genomes. |
Start Year | 2021 |
Description | ENQ-4041 |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Metagenomic data generation of bacterial and fungal communities in the rhizosphere |
Collaborator Contribution | Provision of materials |
Impact | Metagenomic resources to characterise the functional genome in bacterial and fungal communities in the rhizosphere |
Start Year | 2020 |
Description | ENQ-4137 |
Organisation | University of East Anglia |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Genome data generation of human samples |
Collaborator Contribution | Provision of materials |
Impact | Genomic resources to better understand variation in human samples |
Start Year | 2020 |
Description | ENQ-4355 |
Organisation | Imperial College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Transcriptomic data generation of fungal pathogens causing disease in amphibians |
Collaborator Contribution | Provision of materials |
Impact | Transcriptomic resources to understand variation in different lineages of a fungal pathogen. |
Start Year | 2020 |
Description | ENQ-4467 |
Organisation | Oxford Nanopore Technologies |
Country | United Kingdom |
Sector | Private |
PI Contribution | Transcriptomic data generation for benchmarking |
Collaborator Contribution | Provision of materials |
Impact | Transcriptomic resources for benchmarking. |
Start Year | 2020 |
Description | BBC Radio Norfolk Interview on Norfolk Day |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Dr Karim Gharbi was interviewed with by BBC Radio Norfolk host Stephen Bumfrey on the 27th of July, 2019 to celebrate Norfolk Day and Norwich Research Park. The interview was pre-recorded from the Earlham Institute's sequencing labs and focused on the cutting-edge technologies used by the Institute and their impact on people's lives. The interview was interactive and involved the radio host navigating the wheat genome using online tools to look at gluten genes, followed by a discussion on gluten intolerance in the human population and associated genetic risks. The interview was recorded in the morning and broadcasted in the afternoon. The recording was also made available on the BBC website for download for 90 days post broadcast. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.bbc.co.uk/programmes/p06bth9z |
Description | Contribution to online science teaching platform |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Schools |
Results and Impact | Dr Karim Gharbi was interviewed by Developing Experts, a Norwich-based company, providing a growing library of over 700 interactive online science lessons with fun science experiments, handouts and assessment for learning activities for children 4 to 14 years. The platform is used by 4,000 home educators and teachers in the UK and abroad. The interview was carried out in situ within the National Capability laboratories in the form short films, which are featured in lessons about DNA, inheritance, and genetics. |
Year(s) Of Engagement Activity | 2018 |
URL | https://developingexperts.com/articles/168 |
Description | Darwin Tree of Life Project (UK) |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Press release detailing the institutes involvement (partner) in the project which will create a new foundation for biology to drive solutions for preserving biodiversity and sustaining human societies. The institute is likely to be involved in the sampling and sequencing of protists (single-celled eukaryotes - organisms with a nucleus) and the analysis of vertebrate genomes. |
Year(s) Of Engagement Activity | 2018 |
Description | Decoding Life on Earth - The Earth BioGenome Project (EBP) |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Press release detailing the institutes involvement (partner) in the project which is a global effort to sequence the genetic code of all 1.5 million known animal, plant, protozoan and fungal species on Earth. The project will create a new foundation for biology to drive solutions for preserving biodiversity and sustaining human societies. The aim is to sequence, catalogue and categorise the genomes of all of Earth's eukaryotic biodiversity over a period of ten years. |
Year(s) Of Engagement Activity | 2018 |
Description | EI boost National Capability in Genomics and Single Cell Analysis with ultra-high throughput sequencing platform |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Press release to announce that Earlham Institute (EI) add Illumina's NovaSeq 6000 to its National Capability in Genomics and Single Cell Analysis, harnessing the power of ultra-high throughput sequencing for Norwich Research Park and the wider bioscience community. News stories highlight important updates that also have broad relevance and interest to the national and/or specialised media. Collectively, our international reach as of March 2019 has extended across the globe, with highlight pieces in the Guardian, the BBC World Service, the Washington Post and more, as well as local TV and radio. In 2018, the estimated readership of news stories we shared was well in excess of 1 million. |
Year(s) Of Engagement Activity | 2018 |
URL | http://www.earlham.ac.uk/newsroom/ei-boost-national-capability-genomics-and-single-cell-analysis-ult... |
Description | Feature article on genomics in the Easton Daily Press |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | The Article was to cover the research activity at the Earlham Institute and at the Norwich Research park and how it would impact the general public |
Year(s) Of Engagement Activity | 2019 |
Description | Immersive Viisit Training Program (LM_18) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The Genomics Pipelines Group hosted a scientist from the Biosciences eastern and central Africa - International Livestock Research Institute (BecA - ILRI) Hub for 1 week. The purpose of the visit was to be introduce to scientist to the latest advances in NGS sequencing platforms (primarily Illumina) from library preparation to platform operation and management, and share best practices. |
Year(s) Of Engagement Activity | 2018 |
Description | Interviewed for a BBC news feature on the Darwin Tree of LIFE project - shown worldwide on BBC world news |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | The feature covered the Darwin Tree of Life project and the involvement of EI. Particularly focussing on Protists |
Year(s) Of Engagement Activity | 2019 |
Description | PhD by experience: Darren Heavens |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Article by Dr Darren Heavens, who after over 30 years' experience in genomics research, from pig breeding to improving wheat yield, went down an alternative PhD route. Articles such as this pertain to our publically funded research such that the information gleaned can be disseminated to the general public. As of March 2019, our articles have reached people in all but 6 countries worldwide, with over 50000 pageviews on our website in the year 2018. On social media, this reach has exceeded a million people, monthly. As part of an expanding portfolio covering the range of science that we do, each article forms a vital component of how we engage the wider international community with important scientific breakthroughs and knowledge. |
Year(s) Of Engagement Activity | 2018 |
URL | http://www.earlham.ac.uk/articles/phd-experience |
Description | Techology Day at Norwich Science Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | 7500 members of the general public attended Nature Day at Norwich Science Festival. A number of activities were available to engage the general public with the work of the institute. A number of talks/presentations were scheduled also. |
Year(s) Of Engagement Activity | 2018 |
Description | What doesn't kill you makes you stronger? Cracking Salmonella and antibiotic resistance |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Article on tackling Salmonella by exploring a highly mutable, evolved strain to help answer why antibiotics are becoming less effective and improve our bodies' antimicrobial armour. |
Year(s) Of Engagement Activity | 2018 |