Empowering research with ultra-fast high-throughput genome sequencing on the benchtop

Lead Research Organisation: University of Aberdeen
Department Name: Inst of Biological and Environmental Sci


Biological research is in the midst of a revolutionary change. This revolution is being driven by the explosive increase in our ability to rapidly and cheaply sequence whole genomes which has gone from taking 10 years to sequence a human genome to just 1 day. Such an information explosion is spurring massive advances in biological research across many disciplines, and holds tremendous promise for surmounting many of the major challenges facing the UK and the world, including improved human health, sustainable food production, protection of the environment, and renewable bioenergy. From its inception such NGS technology has generally been provided as a service to researchers by large-scale sequencing 'factories' with the financial capacity to invest in the expensive capital equipment required. Though effective, such service providers tend to lack flexibility and responsiveness, raising barriers to the productive uptake of NGS in both smaller laboratories and in fields not traditionally associated with genomics. This has in many ways led to a slower uptake of NGS in many fields of high priority to the BBSRC such as food security, bioenergy and environmental change. The University of Aberdeen is particularly strong in BBSRC funded research relevant to these priority areas, including research into fish physiology, crop genetics, plant and soil interactions, tree pathology, and tick and mite biology. Unfortunately, these communities are under served in this current climate of large-scale NGS providers. Acquisition of the new Illumina NextSeq 500 DNA sequencer within the University of Aberdeen's Centre for Genome-Enabled Biology and Medicine (CGEBM) will help to overcome this barrier to use, leading to an enhanced utilisation of genomics within these currently underserved BBSRC funded research communities at the University of Aberdeen and locally. The new capacity provided by the NextSeq 500 will also enable Aberdeen's continued excellence in research relating to human health, including healthy ageing and infection biology; areas where researchers at the University of Aberdeen have been exploiting high through put genomics for over a decade. Further, it is our experience that initiation of new applications of NGS that make real advances in understanding, often requires developmental work, which is more easily achieved through direct interaction with those running the facilities, a process made much easier if these facilities are local.

Technical Summary

Genomics capacity is widespread in the UK and globally with currently seven HiSeq instruments in Scotland available to researchers in Aberdeen, with six of these in Edinburgh. However, Edinburgh is geographically distant to Aberdeen limiting both interactive design and development of projects, and training and the growth of the local research base. The University of Aberdeen's Centre for Genome-Enabled Biology and Medicine (CGEBM) currently has Miseq (Illumina) and Ion Proton (Life Technologies) sequencers for NGS. The MiSeq has a capacity for 15Gb sequence output and 25M 300 nucleotide paired end reads per run. The Ion Proton has a current capacity of 15 Gb sequence output and 90M 200 nucleotide single end reads per run. These instruments provide a platform to perform whole genome re-sequencing of prokaryotes and genetic model eukaryotes with relatively small genomes (e.g. yeast, Caenorhabditis elegans, Arabidopsis thaliana), metagenomic and transcriptomic analyses of complex microbial samples, exome sequencing, and small-scale ChIP-seq and RNA-seq. However, due to the relatively lower throughput of these instruments researchers cannot currently perform locally more data-intensive NGS applications. The NextSeq 500 with its cost effective capability for 120 Gb of sequence and 400M reads in 29hr provides an ideal system to overcome the limitations of the MiSeq and Ion Proton. The NextSeq 500 will allow researchers to perform the full range of NGS applications, including de novo genome sequencing in most eukaryotes, population-scale genotyping by re-sequencing, as well as applications requiring increased sequencing depth such as transcript discovery, detection of rare transcripts, and analysis of highly complex amplicon libraries (e.g. eukaryotic and prokaryotic metagenomics and metatranscriptomics, and complex RNAi libraries).

Planned Impact

Given the focus of the proposed research on enhancing capacity to perform genomics, we have designed multiple knowledge exchange activities with the deliverable of increasing the wider public's awareness of genomics and the genome. To increase the impact of the proposed knowledge exchange activities where possible they will be linked to the University of Aberdeen's May Festival, a cultural event with a wide variety of activities that span the themes of Word, Music, Film, Science, Gaelic, Environment, Health & Wellbeing and Discovery, attracting ~7,500 visitors annually to attend over 100 events. The diverse set of activities planned are designed to enable a dialogue between the public and working scientists around genomics and its societal impacts. This dialogue will utilize the media of the spoke and written word, the visual arts and the living world, and will engage various sections of the public, including those interested in science, visual arts and nature. There are four planned knowledge exchange programmes:

1. Develop an educational installation within the Cruickshank Botanic Gardens focused on genomics. This installation will include a combined living-plant art work and experiment, created from a diverse set of 1001 different Arabidopsis thaliana ecotypes collected from across the world. This diverse set of plants will be grown in blocks forming a double helix, and over a 3-year period the diversity in size, leaf shape and flowering time will be documented photographically. Informative signage will be included as part of the installation with the learning objective of familiarising the public with the term 'Genome' and how even a humble weed growing throughout Aberdeen (Arabidopsis thaliana) can play a critical role in helping us understand how the genome functions.

2. The Curator of the CBG, Mark Paterson, presents a weekly radio show on shmuFM called Growth Matters. Prof Salt will make regular appearances (four per year) on Growth Matters to highlight the genomics installation and discuss genomics and its relationship to horticulture. Growth Matters is a show for Aberdeen City gardeners, broadcast every Tuesday that will provide an excellent venue for Prof Salt to engage with the local community on issues relating to genomics and plants.

3. To reach a wider audience beyond those with a current interest in plants Prof Salt is contracted to publish an essay describing the evolution of the term Genome from its inception to the present day. Prof Salt will present public discussions based on this essay in the Café Scientifique series and PechaKucha Nights in Aberdeen City. The Café Scientifique series is a community cafe programme that generally attracts members of the public with an interest in science. PechaKucha Nights are now running in over 500 cities across the world including Aberdeen, bringing people together in a relaxed, simple and enjoyable format to meet, network and share ideas and work in public. These events generally attract people from the arts community.

4. To reach out to members of the public interested in visual culture, who may not have a current interest in science, we plan to hold the Genome Illustrated Prize which asks the "question of how we can represent Genomes in contemporary art, and what this can convey visually". Works will be exhibited at Seventeen, a Centre for the Arts in the heart of Aberdeen City Centre.

We also expect to directly impact industry and the public sector through collaborative arrangements for use of the NextSeq 500, managed by the CGEBM. Specifically, we will collaborate with the NHS Grampian genetics laboratory which provides regional and national genetics and molecular pathology laboratory services to NHS Scotland, and NCIMB Ltd which maintains the UKs reference collection of industrial, food and marine bacteria and provides commercial microbiological testing to the oil and gas, pharmaceutical, food and environmental sectors.


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Title 1001 Genomes Garden 
Description A living multi-year artwork created by planting the 1001 Arabidopsis thaliana accessions that have had their genomes sequences. Plants were planted in the shape of a double helix in the Cruickshank Botanic Gardens at the University of Aberdeen accessible to the public, students and staff. 
Type Of Art Artwork 
Year Produced 2015 
Impact Viewed by >100 people 
Description We have purchased a NextSeq500 next generation sequencer and supporting liquid handling robotics for the Centre for Genome Enabled Biology at the University of Aberdeen which currently has a portfolio of over 70 different sequencing projects covering research on plants, animals and microbes. To date the NextSeq500 has supported numerous projects, including sequencing projects on rice, salmon, siberian hamster, Laccaria bicolor and mouse. These projects consist of a) Industrial CASE studentship: Characterization of copy number variation in Atlantic salmon. b) RNA methylation plasticity: Light induced changes in hamster hypothalamic RNA methylation. c) How intra- and interspecific diversity of ectomycorrhizal fungi regulates ecosystem functioning: Linking functional diversity to genomic diversity. d) Transcriptomics study of rice in response to alternate wetting and drying irrigation. e) Genome-wide DNA binding studies to interrogate retinoic acid receptor signalling in models of obesity and type 2 diabetes. f) RNAseq studies to interrogate retinoic acid receptor signalling in models of obesity and type 2 diabetes.
Exploitation Route The use of the NextSeq500 has allowed researchers from the School of Biological Sciences, School of Medical Sciences, The Rowett Institute of Nutrition and Health and Department of Archaeology to progress diverse projects including ancient DNA of dogs, rice genomics, shark genomics, human cancer studies, gut meta genomics, medically important yeasts and single cell genomics.
Sectors Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology

URL http://www.abdn.ac.uk/genomics/
Description Impact of fungal adaptation upon host recognition and pathogenesis. PI, Professor Alistair Brown. CoIs, Professors Neil Gow, Lars Erwig, Mihai Netea.
Amount £1,981,419 (GBP)
Funding ID MR/M026663/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Description The transition from fungal commensalism to systemic infection. PI, Professor Alistair Brown. CoIs, Professor Gordon Brown, Dr Donna MacCallum.
Amount £108,653 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Bloomsbury Centre
Sector Charity/Non Profit
Country United Kingdom
Description responsive mode
Amount £514,378 (GBP)
Funding ID BB/N023927/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2017 
End 12/2020
Title The NextSeq500 has been fully integrated into the CGEBM infrastructure 
Description The NextSeq500 has been fully integrated into the CGEBM infrastructure. CGEBM laboratory personnel have developed comprehensive, in depth expertise in the preparation of samples for new applications using the NextSeq500 and are fully competent in instrument operation and maintenance. The CGEBM bioinformatics team have developed expertise and established robust pipelines for analysis of the diverse datasets that have been generated using the NextSeq500 to date. The funding for a robust and secure long-term archive solution for data storage, enabled the UoA IT services department to test and establish this new infrastructure with Arkivum, a commercial tape archive service, available through the JANET data archive framework. This provided a local data management hub (Linux OZ server appliance) to curate, process, compress and transfer data and capacity of 10Tb base operational storage for genomics datasets generated as part of this initiative. The curation functionality ensures standardised recording and structure of data for improved data tracking and management. This solution is cost-effective and scalable, and is highly secure with data stored on tape in 3 geographically separated locations, including 2 in 3rd party escrow and a 'no lost bit' financial guarantee. Importantly, the success of this initiative led to further investment by UoA to establish this as an institute wide archive solution. 
Type Of Material Improvements to research infrastructure 
Year Produced 2015 
Provided To Others? Yes  
Impact The enhanced sequencing capacity provided by the ALERT14 funding has enabled the breadth of applications and research questions that can be addressed to be significantly expanded. The applications supported by this instrument to date include RNAseq for differential expression analysis of small and large transcriptomes, de novo whole transcriptome and whole genome sequencing (WGS), single cell WGS, resequencing for variant detection, ChIPseq for genome wide analysis of transcription factors, BIS-RNAseq for analysis of transcriptome methylation, and BarSeq/ TnSeq for mutant library profiling under different conditions. These projects include a diverse array of organisms and biological systems, including plant and clinical fungal species, model and non-model mammals, rice, salmon, archaea, bacteria, virus and shark. This encompasses 29 different projects led by 19 PIs. This enhanced infrastructure has been successfully incorporated into the CGEBM business model ensuring continuity and long-term accessibility to this technology. Importantly, delivery of this infrastructure within the CGEBM model has enabled pump priming of early career researchers and doctoral students, through financial support and extensive specialist training in genomics and bioinformatics. CGEBM laboratory staff provide guidance and training in aspects relevant to sample collection and processing and in specialist techniques required for sequencing on this instrument. Furthermore, a comprehensive bioinformatics training portfolio has been developed by CGEBM (http://www.abdn.ac.uk/genomics/bioinformatics/training/) and this has been modified and expanded to incorporate the specific applications and data sets supported by the enhanced sequencing capacity enabled by the ALERT14 funding. These workshops have been well attended with strong positive feedback from delegates. University of Aberdeen delegates are from life sciences, chemistry, computer sciences, geosciences and engineering, as well as local external institutes (NCIMB, NHS Grampian and Marine Sciences Scotland) and other Universities (Universities of Glasgow, Edinburgh, St Andrews, Nottingham). These workshops, in addition to enhancing the skills of local life science researchers, provide opportunities for interdisciplinary networking and knowledge sharing. 
URL https://www.abdn.ac.uk/genomics/
Description 'Explorathon' event in Aberdeen, a Scottish wide event celebrating scientific research as part of European Researchers' Night (ERN) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Explorathon event in Aberdeen, a Scottish wide event celebrating scientific research as part of European Researchers' Night (ERN), co-ordinated by the European Commission in 250 cities across Europe. UoA leads Explorathon in Scotland, with 1900 interactions in Aberdeen and 3.3M Twitter impressions.
Year(s) Of Engagement Activity 2016
URL http://www.abdn.ac.uk/engage/staff-students/european-researchers-night--341.php
Description Doors Open Day in which public buildings are opened to the public for free 
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 The Doors Open Day at the Institute of Medical Sciences (IMS) in which public buildings are opened to the public for free. It is co-ordinated nationally by the Scottish Civic Trust and constitutes Scotland's contribution to European Heritage Days with over 10 000 visitors across Scotland and 180 to the IMS.
Year(s) Of Engagement Activity 2016
Description The Genome Analysis Center 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The Genome Analysis Center (TGAC) Science Symposium, 16th Sept, 2015.
Year(s) Of Engagement Activity 2015