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

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.

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).

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.