Innovation and excellence in science and health



Genomics England Ltd (GEL)- BRC is leading the pilot for GEL’s 100,000 genomes project, focused on whole genomes of infectious agents and patients with cancer and rare diseases
- within the eHospital programme, BRC is providing the infrastructure for the integration of genomic and clinical information
- BRC facilities will complement GEL by rapidly generating reports to clinical accreditation standards for bespoke sequencing applications (ctDNA, epigenomic analyses, pathogen sequencing, specific gene panels for mosaicism etc)
- transferring SOPs, validation documentation etc., developed in the NIHR BRC and NHS molecular genetics laboratories, which meet UKAS/CPA and ISO requirements for NHS clinical diagnostic test
- in parallel, the NIHR BioResource – Rare Diseases led by the NIHR Cambridge BRC is committed to whole exome and whole genome sequencing of patients with rare diseases
East of England NHS Genomic Medicine Centre
CRUK Cambridge Institute Genomics Core Facility - provides access to state-of-the-art DNA and RNA analysis instruments, methods and applications, and in particular next generation sequencing
- all data generated using next-generation DNA sequencing (NGS), microarrays or quantitative real-time PCR (qPCR)
- multiple Illumina NGS instruments, allowing unbiased genome-wide experiments to be performed that enable researchers to see, at base-pair resolution, what the underlying sequence differences are in cancer genomes
- currently using commercial microarray systems from Illumina, Agilent and Affymetrix to analyse, among others: gene expression, gene copy number, methylation, and microRNA expression - much of this work is being supplanted by NGS
CAmbridge Translational GenOmics (CATGO)- co-funded by NIHR through the Cambridge Biomedical Research Centre, the NIHR BioResource – Rare Diseases and NHS Blood and Transplant (NHSBT)
- through the NIHR BioResource – Rare Diseases, provides clinical researchers access to whole genome sequencing (WGS) to clinical standard (>30x read depth on average)

- WGS capacity for 10,000 samples provided by Illumina Cambridge); agreed production targets are 3,500 for 2014 (2,000 for Genomics England Ltd), 5,000 for 2015 and another ~8,000 for 2016
- BRC and NIHR BioResource – Rare Diseases ran the key pilot project for rare diseases with Genomics England Ltd in 2014

- in parallel, the Whole Exome Sequencing pipeline has been stabilized and 760 NIHR BioResource – Rare Disease samples have been sequenced and variants called (a first pass analysis showed a robust level discovery of novel rare disease genes)

- after the success in 2011/12 of transferring clinical sequencing of BRCA1/2 and Stickler Syndrome genes from classic Sanger sequencing to a next generation sequencing (NGS) platform, focus switched during 2013 to the validation of a NGS platform for 94 genes underlying the plethora of Mendelian platelet and bleeding disorders and the 6 genes underlying pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT); this NGS platform went into routine production during 2014 and was made accessible to the 24 Haemophilia and PAH/HHT comprehensive care centres across the UK for use in patient diagnosis

- key strength is the combined power of patient resources enrolled through the NIHR BioResource and genome sequencing to study rare diseases.

- partnership with the University’s High Performance Computing Service (HPC - Dr Paul Calleja) has been expanded and back-up storage of sequencing files (BAM, gVCF) has been secured through a partnership with the European Bioinformatics Institute (Dr Ewan Birney)

Clinical Translational Research Unit (CTRU)- develops, validates and translates genomic research into routine clinical diagnostic service
- ext generation sequencing (NGS) platforms include an Illumina HiSeq 2500, 3 Illumina MiSeq’s and 2 Ion Torrent PGM’s. The unit has experience in library preparation, targeted enrichment, NGS and bioinformaticsestablished in early 2013
- located within the Regional Molecular Genetics laboratory
- supported by the NIHR Cambridge Biomedical Research Centre

East Anglian Medical Genetics Service - offers cytogenetic (chromosome) and molecular genetic (DNA) analysis
The European Bioinformatics InstituteEMBL-EBI, can provide access to data, expertise, skills and training to support clinical research and precision medicine.
EMBL-EBI provides freely available data from life science experiments covering the full spectrum of molecular biology and is best known for:
• Provision of bioinformatics services - We maintain the world’s most comprehensive range of freely available and up-to-date molecular databases. Developed in collaboration with our colleagues worldwide, our databases and tools span the full range of molecular biology, from nucleotide sequences to full systems.
• Basic research - EMBL-EBI provides a unique environment for bioinformatics research, and our broad palette of research interests compliments our data resources. In the era of personal genomics, our research is increasingly translational and related to problems of direct significance to medicine and the environment.
• Training - extensive training programmes designed to help researchers in academia and industry to make the most of the incredible amount of data being produced every day in life science experiments.
Molecular biology has a close relationship with computational science, particularly in regards to the gathering, dissemination and analysis of data from high-throughput experiments and is becoming increasingly relevant to clinical research and precision medicine. This is because the fundamental processes of living organisms are driven by molecular events, and because the costs of automated data-gathering technologies – most notably DNA sequencing but also proteomics and metabolomics – have dropped precipitously over the past decade and continue to fall. Coupled with cost–effective imaging techniques, a large amount of data can be gathered and integrated to help inform both clinical research and precision medicine. As such EMBL-EBI can provide access to relevant data and expertise including:
• Annotation of variants of clinical importance in different diseases;
• Annotation of somatic variants and genes, and their association with drugs;
• Cataloguing and understanding small molecule/drug interactions with proteins and protein variants, including their 3-D structure interactions and pharmokinetic parameters;
• Cataloguing and understanding human pathogens and their virulence components;
• Cataloguing and understanding biomarkers (e.g. protein, RNA, metabolites) for diagnosis and disease monitoring;
• Capturing and making available molecular profiles that characterise differences between diseased and normal states, or providing sub-classification of a disease;
• Developing resources that are fundamentally about understanding biology, in particular the molecular basis of human disease.
Rather than seeking to hold all the answers, EMBL-EBI resources are characterised by tight partnerships with other leading groups in Europe. Within these partnerships, we offer our engineering, algorithmic and statistical expertise, as well as an in-depth understanding of all manner of biomolecular datasets. As such EMBL-EBI would be extremely keen to partner with the Precision Medicine Catapult.
The Wellcome Trust Sanger InstituteCharitably funded genomic research centre south of Cambridge in the UK. The Institute is an internationally recognised leader in genomics research with teams focusing on understanding the role of genes in health and disease including in cancer, infectious, metabolic or rare diseases. The extraordinary scientific output of the Sanger Institute is driven by its ambition to tackle projects on a big scale and is powered by cutting edge platforms, such as genomics, bioinformatics and a systematic approach to the production of models such as human iPS Cells. The Sanger Institute aims to provide results that can be translated into diagnostics, treatments or therapies that reduce health burdens globally. The Sanger Institute in few numbers and PM relevant fact:

· 1100 staff
· ± £100M/year operation
• Current translational activities include:
o developing genomics resources and interpretation pipelines for use in the hospital clinical microbiology laboratory and
o developing resources and interpretation pipelines for prenatal diagnostics
o using cancer cell screens coupled to the power of sequencing and bioinformatics to discover biomarker of cancer drug sensitivity or resistance.
· Two spinouts funded in 2014 addressing the need of the precision medicine field:
o 14M Genomics ( a cancer diagnostic company
o Congenica ( developing clinical genomic analytics platform for treatment, patient stratification and improved therapeutic discoveries
· Developing the genome campus to support science, innovation and education in genomics:
o Campus will host the Genomic England Ltd facility
GEL is a company owned by the Department of Health set up to deliver the 100,000 Genomes Project. This flagship project will sequence 100,000 whole genomes from NHS patients by 2017, generating a uniquely rich dataset;

o Campus will host a big data - focussed incubator to foster innovation based on genomics data and technologies with the long view that their implementation will deliver better health.

· Other Institute output:

o 300 papers/year, over 50 in top 5 journals

o Databases

o Software

o Biological resource

o For example, in 2016 we plan to deliver

§ 4,000 cancer/normal genome sequences

§ 40,000 human genome sequences from healthy individuals or with disease

§ Genome sequences of >30,000 bacteria, viruses and parasites

§ Human iPS stem cell lines for research from 2000 healthy individuals or with disease

· Largest DNA sequencing facility in Europe

Interaction with the PM catapult:

The mission of the Sanger Institute includes active translation of its discoveries, technologies and resource. We achieve this by engaging with R&D, clinical and funding communities to promote the real world utilization of our scientific output. The genomics research of the Sanger Institute provides a natural fit to the field of precision medicine. We are always actively seeking to network and partner with organisations who can help us deliver health benefit from our scientific research, particularly in the field of diagnostics and drug discovery.
14M Genomics14M Genomics is a cancer diagnostic company working in partnership with the Wellcome Trust Sanger Institute to enrich the understanding of the role of cancer genes in the biology of disease
CongenicaStart-up company founded on pioneering research from the Wellcome Trust Sanger Institute, NHS clinicians and genetic testing laboratories. We are translating this research into a revolutionary clinical genomic analytics platform, SAPIENTIA™, for processing genome-wide data sets of human DNA sequence with deep clinical phenotype information in order to provide a definitive molecular diagnosis and clinically actionable interpretation for treatment, patient stratification and improved therapeutic discoveries.
Eagle Genomicsdelivers products and expert services to unleash the power of large scale data to real-world problems. Blending science, technology, and informatics, Eagle addresses key challenges in healthcare, food and consumer goods. Through its genomic data analysis platform and services, Eagle transforms business through genetic data insights.
Illumina- Illumina has two facilities in Cambridge and multiple collaborations with campus researchers
- NIHR Cambridge BRC completed tender process leading to award of contract with Illumina for WGS of 10,000 pateints recruited to Genomics England pilot and NIHR BioResource Rare Diseases


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