Leading the way Highlights 2018/19 World-class 02 research and What we do innovation 02 Director’s Introduction that impacts 04 At a Glance people’s lives Through our cutting-edge infrastructure, scientific independence and innovative ideas we engage in long-term exploratory projects that drive forward science Wherever you see this dark blue text or yellow, click to find more information. Read more about our ground-breaking research into Parasites and Microbes Page 26 sanger.ac.uk What we do Our work Our approach Other information 08 Our work 10 Cancer, Ageing and Somatic Mutation 16 Cellular Genetics 20 Human Genetics 26 Parasites and Microbes 34 Tree of Life 40 Our approach 42 Scale 44 Innovation 46 Culture 48 Influence 52 50 Connections Other info 52 Image Credits 53 Institute Information Wellcome Sanger Institute Highlights 2018/19 1 What we do One such project is the UK Biobank Director’s Vanguard project, where our sequencing pipeline is delivering 50,000 volunteers’ Introduction whole-genome sequences to aid genetic he past year has been one of great exploration of health and disease. joy and sadness: we celebrated our By marrying the wealth of genomic data 25th anniversary and we mourned T with electronic health records and other the death of our first director, John Sulston. molecular characterisation tools, our Under John’s guidance, the Sanger Institute researchers have discovered new gene determined one-third of the human reference variants associated with osteoarthritis, genome, providing a fundamental gift to life developed prognostic calculators for science research worldwide. cancer, and created an artificial intelligence It seemed most fitting to seek to make that predicts new pathogen emergence. another foundational gift to science as our Our established approaches continue to main celebration. Our 25 Genomes for 25 deliver important discoveries. Our malaria Years project has delivered high-quality researchers applied genome-wide genomes for UK species for which no saturation mutagenesis to identify reference existed. This work is catalysing Plasmodium falciparium’s essential research and aiding conservation efforts genes, revealing new therapeutic targets. in areas as diverse as golden eagle Discover While our collaboration with the NHS – resettlement and fen raft spider breeding. how we have the Deciphering Developmental Disorders driven forward There is much that genomics can bring to (DDD) project – celebrated its eighth year genomic the ecological issues facing our planet and of delivering diagnoses to children with understanding our communities, and we are proud to developmental disorders. After 125 papers in 2018 have founded a new research programme and more than 4,500 diagnoses, the project – The Tree of Life. It will lead the UK-wide continues to deliver fresh insights into the collaboration between genomic, conservation mechanisms of inheritance, and has identified and ecology partners to produce reference 49 previously unknown genetic disorders. genomes for all 66,000 species of complex As we move into our next quarter century, organisms found in the British Isles. the promise of genomic science to improve This new work will also serve to strengthen health and conservation is greater than our research into human health. A paradigm ever, and we are privileged to help deliver shift in sequencing technologies has the next wave of discovery. opened up routine, high-throughput whole-genome sequencing of human genomes. Advances in single-cell technologies, machine learning, and cellular modelling are dissecting health and disease within single cells in individual tissues, over time. Our challenge and goal is to lead the way in extracting the maximum value from this data. Professor Sir Mike Stratton, Director Wellcome Sanger Institute 2 Wellcome Sanger Institute Highlights 2018/19 What we do Our work Our approach Other information Wellcome Sanger Institute Highlights 2018/19 3 At a Glance In 2018, the In 2018, we read The human genome Sequencing Centre the genomes of is approximately outputted almost 7,558bn 338 3bn DNA bases species bases long a day In 2018, the In 2018, we Sequencing Centre read the equivalent provided the equivalent of of one gold-standard (30x) human genome every 588 gold-standard (30x) 17 mins human genomes a week encing Cen qu tr Se e D ata Centre Centre-based Usable storage high performance in the Data Centre compute cores 20,000 55PB Total number of Centre-based Network backbone compute cores cloud-based flexible speed compute cores 32,000 12,000 400GB/sec 4 Wellcome Sanger Institute Highlights 2018/19 2018 timeline Institute’s founding director, John Sulston, died Page 47 Malaria screen Sarah Teichmann finds genes essential awarded Genetics for life Society’s 2018 Page 31 Mary Lyon NCTC 3000 Medal HDR UK funding genomes reveal for Cambridge hub antibiotic resistance Innovations’ history Adrian Ibrahim chairs new BIA Microbiotica Genomics Seeds of kidney and Genentech Advisory cancer sown in sign strategic Committee adolescence partnership Jan Feb Mar Apr May Jun New osteoarthritis Celgene joins genes discovered Open Targets Machine learning flags potential pathogens Dominic Kwiatkowski Multidrug resistant joins Fellowship malaria spread under of the Royal the radar for years Society in Cambodia Peter Campbell honoured by EMBO Cholera tracked at household level Page 28 UK Biobank agreement to sequence 50,000 human genomes Page 43 Skin is a battlefield for mutations Page 10 Largest collection of worm reference Blood test genomes produced could predict Page 27 leukaemia Page 11 Human Cell Personalised Atlas boosted by prediction of Wellcome funding blood cancers Kidney cancer’s Sanofi joins developmental Open Targets source revealed Jul Aug Sep Oct Nov Dec Genome damage Rare genetic Launch of UK from CRISPR-Cas9 diseases more Darwin Tree of Life editing more complex than Project to support extensive than thought Earth BioGenome thought Project AI-created CRISPR-Cas9 editing prediction tool Golden eagle 25 Genomes for genome sequenced 25 Years project Page 39 Page 34 IT’s award winning cloud compute Page 42 What we do Our work Our approach Other information Year in numbers 507 7.398 Institute Petabases publications in 2018 4.639 Pb Cell 4 3.025 Pb Nature 21 1.910 Pb Nature Genetics 16 1.054 Pb New England Journal of Medicine 1 Jan 2015 Jan 2016 Jan 2017 Jan 2018 Jan 2019 Science 14 Who published Where Sanger How much DNA our work? staff are from* was sequenced? 1,236 Europe 63 North America 7 Middle 100 East Asia Pacific 16 12 Africa Latin America *In January 2019 Wellcome Sanger Institute Highlights 2018/19 7 Our work With secured funding from Wellcome, we are able to strategically focus our work in five key research fields 10 Cancer, Ageing 26 Parasites and Somatic and Microbes Mutation Investigates the common underpinning mechanisms of evolution, infection Provides leadership in data aggregation and resistance to therapy in bacteria and informatics innovation, develops and parasites. It also explores the high-throughput cellular models of cancer genetics of host response to infection for genome-wide functional screens and the role of the microbiota in health and drug testing, and explores somatic and disease. mutation’s role in clonal evolution, ageing and development. 34 Tree of Life 16 Cellular Investigates the diversity of complex organisms found in the UK through Genetics sequencing and cellular technologies. It also compares and contrasts species’ Explores human gene function by studying genome sequences to unlock the impact of genome variation on cell evolutionary insights. biology. Large-scale systematic screens are used to discover the impact of naturally-occurring and engineered genome mutations in human iPS cells, their differentiated derivatives, and other cell types. 20 Human Genetics Applies genomics to population-scale studies to identify the causal variants and pathways involved in human disease and their effects on cell biology. It also models developmental disorders to explore which physical aspects might be reversible. 8 Wellcome Sanger Institute Highlights 2018/19 What we do Our work Our approach Other information Discover how we tracked cholera house by house Page 28 Read how Himalayan genomes show how humans adapted to high altitudes Page 24 Find out how we use single-cell techniques to explore foetal development Page 19 Wellcome Sanger Institute Highlights 2018/19 9 Cancer, Ageing and Somatic Mutation In this section 1 Your body: a Darwinian battlefield 2 Blood test could predict leukaemia 3 One-stop shop for cancer models 4 Cancer calculator gives personalised predictions 5 Genomic microscope sorts lions from lambs 6 ‘Fast’ bone cancer has slow origins 7 Cancer’s seeds sown decades earlier 8 Ecological approach reveals hidden stem cell population 1 Your body: a Darwinian battlefield Research by Sanger Institute cancer researchers, published in Science and Cell Stem Cell, reveals that our bodies are evolutionary battlefields where only the fittest cells survive. s our bodies age, our cells acquire by other clones. Even when the mice were While further work is needed to answer such an increasing amount of mutations exposed to UV light, mimicking the effects questions, the results show the fundamental A in their genomes, making cancer of the sun, the clones with cancer importance of considering healthy tissue development ever more likely. While much mutations didn’t survive and progress when studying the origins of cancer. work has been undertaken to understand to tumour formation. the mutations that lead to tumour formation, much less is known about how healthy Much to the researchers’ surprise, the tissue changes over time. For example, in same was true in oesophageal tissue. 2015, Sanger scientists showed that 25 per Despite being shielded from UV light, References a large proportion of the cells carried Martincorena I et al. High burden and pervasive cent of eyelid cells in people without cancer positive selection of somatic mutations in normal cancer-associated mutations.