High throughput Sequencing Hub for the North of England
Lead Research Organisation:
University of Liverpool
Department Name: Sch of Biological Sciences
Abstract
DNA sequence has always been an important source of inspiration for advances in medical and clinical research. This culminated in the sequencing of the first human genome, a project that took 6-8 years and several billion pounds. As a result we were able to discover the number and identity of genes that defined the human form though it is taking much longer to work out how these genes interact. But we know that people vary from each other in their disease susceptibility or in the way that they respond to treatment. The current need is to understand the basis of this variation and to use it to understand more fully how to define the most appropriate treatment to particular patients presenting with a particular condition. This is called ?personalised medicine? and it is widely thought to be the best way of optimising treatment.
Achieving this requires establishing the DNA sequence of particular genes in those patients, and this requires much more productive sequencing technologies. Fortunately, new instruments are now becoming available which can sequence a human in just a few weeks for approx #10-50,000. The Advanced Genomics Facility (AGF), located in Liverpool, is a leading UK centre of excellence and service provider for the new generation of sequencing technologies. We want to expand the capacity of the AGF to serve the research leaders in Universities and hospitals of the North of England by offering a one-stop shop that provides advice for all stages of the work. We shall also provide training and pump-prime cost-sharing programmes helping client groups to turn DNA sequence into knowledge.
Achieving this requires establishing the DNA sequence of particular genes in those patients, and this requires much more productive sequencing technologies. Fortunately, new instruments are now becoming available which can sequence a human in just a few weeks for approx #10-50,000. The Advanced Genomics Facility (AGF), located in Liverpool, is a leading UK centre of excellence and service provider for the new generation of sequencing technologies. We want to expand the capacity of the AGF to serve the research leaders in Universities and hospitals of the North of England by offering a one-stop shop that provides advice for all stages of the work. We shall also provide training and pump-prime cost-sharing programmes helping client groups to turn DNA sequence into knowledge.
Technical Summary
The North of England has substantial amounts of class-leading medical and clinical research based in major Universities and NHS Trusts, all of which would benefit greatly from access to second generation (2G) DNA sequencing technology, particularly in meeting the challenges of tumour sequencing, genetic susceptibility and personalised medicine. The Advanced Genomics Facility (AGF), located in Liverpool, is a leading UK centre of excellence and service provider for nextgen sequencing. We propose to expand the capacity of the AGF to serve the MRC-related interests in the Universities and NHS Trusts in a consortium covering Liverpool (lead), Manchester, Sheffield, and Lancaster. We shall provide expert access to all three major second generation (2G) technologies, to informatic processing and analysis techniques, and in the medium-term to third generation (3G) technologies. We shall provide training and pump-prime cost-sharing programmes helping client groups to turn DNA sequence into knowledge. Important points in the favour of the AGF include: a strong track record of servicing academic clients; a leading edge position in genome science and sequencing technology; an experienced workforce; minimised consumables costs; multiple platforms; expert informatics capability; a mature open door policy on research collaboration; a training and translation strategy; close working relationships with 2G technology providers including discussions with a 3G provider; and excellent links into the regional and nextgen sequencing communities.
Publications
Goodhead I
(2010)
A comprehensive genetic analysis of candidate genes regulating response to Trypanosoma congolense infection in mice.
in PLoS neglected tropical diseases
Davies G
(2014)
A genome-wide association study implicates the APOE locus in nonpathological cognitive ageing.
in Molecular psychiatry
Nowell RW
(2017)
A high-coverage draft genome of the mycalesine butterfly Bicyclus anynana.
in GigaScience
Ofon E
(2017)
A polymorphism in the haptoglobin, haptoglobin related protein locus is associated with risk of human sleeping sickness within Cameroonian populations.
in PLoS neglected tropical diseases
Adams SE
(2017)
A randomised clinical study to determine the effect of a toothpaste containing enzymes and proteins on plaque oral microbiome ecology.
in Scientific reports
Quilez J
(2011)
A selective sweep of >8 Mb on chromosome 26 in the Boxer genome.
in BMC genomics
Payton A
(2016)
A TOMM40 poly-T variant modulates gene expression and is associated with vocabulary ability and decline in nonpathologic aging.
in Neurobiology of aging
O'Brien S
(2017)
Adaptation to public goods cheats in .
in Proceedings. Biological sciences
Brenchley R
(2012)
Analysis of the bread wheat genome using whole-genome shotgun sequencing.
in Nature
Rodriguez-Fontenla C
(2014)
Assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies.
in Arthritis & rheumatology (Hoboken, N.J.)
Mitchell AL
(2014)
Association of autoimmune Addison's disease with alleles of STAT4 and GATA3 in European cohorts.
in PloS one
Bronowski C
(2017)
Campylobacter jejuni transcriptome changes during loss of culturability in water.
in PloS one
Ahouty B
(2017)
Candidate genes-based investigation of susceptibility to Human African Trypanosomiasis in Côte d'Ivoire.
in PLoS neglected tropical diseases
Vinkhuyzen AA
(2012)
Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion.
in Translational psychiatry
Moran JC
(2017)
Comparative Transcriptomics Reveals Discrete Survival Responses of and to Sapienic Acid.
in Frontiers in microbiology
Kelly J
(2017)
Composition and diversity of mucosa-associated microbiota along the entire length of the pig gastrointestinal tract; dietary influences.
in Environmental microbiology
Rothwell S
(2016)
Dense genotyping of immune-related loci in idiopathic inflammatory myopathies confirms HLA alleles as the strongest genetic risk factor and suggests different genetic background for major clinical subgroups.
in Annals of the rheumatic diseases
Cornick JE
(2017)
Epidemiological and Molecular Characterization of an Invasive Group A Streptococcus 32.2 Outbreak.
in Journal of clinical microbiology
Sniekers S
(2017)
Erratum: Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence.
in Nature genetics
Hackinger S
(2017)
Evaluation of shared genetic aetiology between osteoarthritis and bone mineral density identifies SMAD3 as a novel osteoarthritis risk locus.
in Human molecular genetics
Elliott KS
(2013)
Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data.
in Annals of the rheumatic diseases
Lopez LM
(2012)
Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts.
in European journal of human genetics : EJHG
Alsaadi MM
(2012)
From a single whole exome read to notions of clinical screening: primary ciliary dyskinesia and RSPH9 p.Lys268del in the Arabian Peninsula.
in Annals of human genetics
| Description | BBSRC responsive mode |
| Amount | £433,798 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2011 |
| End | 03/2013 |
| Title | DNA sequence data |
| Description | Every week we generate >10gb DNA sequence from range of samples provided by collaborating groups. This can be from human/plants/microbes or animals. |
| Type Of Material | Database/Collection of Data/Biological Samples |
| Year Produced | 2006 |
| Provided To Others? | Yes |
| Impact | Our data has been used to develop new tools such as Pyronoyes (Quince et al) and RY mapper (Ashelford et al). It has fed into databases such as EUPAthDB. |
| Description | Collaborations with Unilever |
| Organisation | Unilever |
| Department | Unilever UK R&D Centre Port Sunlight |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Genome data generation to underpin programs in personal and home care divisions of Unilever. |
| Collaborator Contribution | Provision of materials. |
| Impact | Better understanding within Unilever of microbial communities as relevant to personal and home care. |
| Start Year | 2013 |
| Description | NHS PhD fellowship Julie Sibbering |
| Organisation | Liverpool Womens NHS Foundation Trust |
| Department | Liverpool Women's Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | We are hosting an NHS research Fellow. Julie Sibbering was working in the clinical diagnostics lab at the liverpool womens hostpital and was awarded the fellowship to work in my lab of Next-gen sequencing methods to identify chromosome abnormalities. |
| Collaborator Contribution | Julie Sibbering brings expertise in clinical diagnostics to the group. |
| Impact | Funding from NHS for fellowship. Training for the student. |
| Start Year | 2009 |
| Description | PHE HPRU |
| Organisation | Public Health England |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | The CGR is a key part of the sequencing capability for Public Health Protection research unit. Part of the CGR |
| Collaborator Contribution | They have provided samples and expertise which have allowed our group to be part of publications and to develop piplines and analyses for other projects. |
| Impact | Several papers on the analysis of west african ebola |
| Start Year | 2014 |
| Description | School teacher training |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Primary Audience | Schools |
| Results and Impact | A group of teachers from a local school came for CPD training in modern biological techniques. They received presentation and hands on experience using genomic technology The school reported this was the best CPD they ever had. |
| Year(s) Of Engagement Activity | 2010 |