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
Tachmazidou I
(2017)
Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits.
in American journal of human genetics
Luciano M
(2012)
Genome-wide association uncovers shared genetic effects among personality traits and mood states.
in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Hamilton G
(2012)
The role of ECE1 variants in cognitive ability in old age and Alzheimer's disease risk.
in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Baird AE
(2014)
Genome-wide association study identifies genomic regions of association for cruciate ligament rupture in Newfoundland dogs.
in Animal genetics
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
Hudson G
(2013)
No evidence of an association between mitochondrial DNA variants and osteoarthritis in 7393 cases and 5122 controls.
in Annals of the rheumatic diseases
Panoutsopoulou K
(2017)
Radiographic endophenotyping in hip osteoarthritis improves the precision of genetic association analysis.
in Annals of the rheumatic diseases
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
Peters MJ
(2013)
Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region.
in Annals of the rheumatic diseases
Jani M
(2014)
Genotyping of immune-related genetic variants identifies TYK2 as a novel associated locus for idiopathic inflammatory myopathies.
in Annals of the rheumatic diseases
Lilleker JB
(2018)
Response to: 'Antisynthetase syndrome or what else? Different perspectives indicate the need for new classification criteria' by Cavagna .
in Annals of the rheumatic diseases
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
Lilleker JB
(2018)
The EuroMyositis registry: an international collaborative tool to facilitate myositis research.
in Annals of the rheumatic diseases
Chinoy H
(2012)
Interaction of HLA-DRB1*03 and smoking for the development of anti-Jo-1 antibodies in adult idiopathic inflammatory myopathies: a European-wide case study.
in Annals of the rheumatic diseases
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.)
Rothwell S
(2017)
Immune-Array Analysis in Sporadic Inclusion Body Myositis Reveals HLA-DRB1 Amino Acid Heterogeneity Across the Myositis Spectrum.
in Arthritis & rheumatology (Hoboken, N.J.)
Miller FW
(2013)
Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.
in Arthritis and rheumatism
Doucet M
(2017)
Quality Matters: 2016 Annual Conference of the National Infrastructures for Biobanking.
in Biopreservation and biobanking
Quilez J
(2011)
A selective sweep of >8 Mb on chromosome 26 in the Boxer genome.
in BMC genomics
Mutwakil MZ
(2017)
Transcriptomic and metabolic responses of Calotropis procera to salt and drought stress.
in BMC plant biology
Lynch JT
(2017)
Inhibiting PI3Kß with AZD8186 Regulates Key Metabolic Pathways in PTEN-Null Tumors.
in Clinical cancer research : an official journal of the American Association for Cancer Research
Baird AE
(2014)
Genetic basis of cranial cruciate ligament rupture (CCLR) in dogs.
in Connective tissue research
Heald AH
(2018)
Route to improving Type 1 diabetes mellitus glycaemic outcomes: real-world evidence taken from the National Diabetes Audit.
in Diabetic medicine : a journal of the British Diabetic Association
| 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 |