Finding out which genetic variants are naughty or nice can be challenging. The Cancer, Ageing and Somatic Mutation teams carry out genetic research to determine the causes and consequences of DNA mutations on the body and over the course of an individual’s life.

This year, our scientists worked alongside their collaborators to understand how specific genetic changes increase a person’s risk of breast and ovarian cancers. They focussed their research on the ‘cancer protection’ gene, RAD51C, which is known to increase breast and ovarian cancer risk by four-fold and six-fold, respectively.¹ By identifying exactly which DNA changes drive cancer development, and those which don’t, we are able to pave the way for personalised care.

Good things come in small packages and that is definitely the case for the Parasites and Microbes programme. Our researchers explore the world of things that are difficult to see with the eye: microbes and parasites. These creatures range from cholera and syphilis to respiratory viruses and parasitic worms. In doing so, they use genomics to understand the evolution of endemic and epidemic infectious diseases.

To delve deeper into infectious diseases, Sanger Institute scientists are collaborating with researchers across the world. This year, the team was awarded a grant from Wellcome led by partners at the icddr,b in Bangladesh to understand how microbes living in the gut or the environment are impacted by climate change and, in turn, affect our health.

Over three years, researchers will work with icddr,b and communities impacted by climate change to collect data about the bacteria living in the gut and environment alongside drinking water to determine their role in climate-related illnesses. This unique partnership could not only provide us with insights to inform future interventions and treatments locally, but it will also create a partnership that will bring together the necessary skills to directly impact and engage with this community. In addition, this project will create data structures and datasets that can be adopted in the future and be of long-term value to this community as well as many others.

Bah, HumGen! Not so much a Charles Dickens’ classic, but definitely a classic here at Sanger. The study of human genetics has always been a core function at the Sanger Institute. The teams within the Human Genetics programme work to discover the mutated genes that are responsible for rare and common diseases.

This year, researchers gained new insights into how common DNA differences can play a role in the development of rare brain conditions. Researchers harnessed the power of data from thousands of children with rare neurodevelopmental conditions and their parents to highlight how common DNA changes may still influence a child’s risk of developing such conditions.

Everyone is rocking around the Tree of Life this year as they reached a milestone of sequencing 2,000 species' reference genomes for the first time. The Tree of Life programme at Sanger was established to help sequence the genomes of all species of life on Earth, starting with those in Britain and Ireland, as part of the Darwin Tree of Life project.

The 2,000th genome to join the collection was the alternate water-milfoil (Myriophyllum alterniflorum), an aquatic plant which has been used to control levels of pollution in rivers and lakes. Other species included in this milestone are the Deathwatch Beetle and plenty of invertebrates including butterflies and moths.

This milestone is also the result of several collaborations, including the European Reference Genome Atlas (ERGA) Pilot Project which aims to generate reference genomes for all eukaryotes in Europe. As part of the pilot, the Tree of Life programme produced 38 genomes including a reference genome for the White-Tailed Sea Eagle (Haliaeetus albicilla) – the UK’s largest bird of prey.

Over the past five years, the team has been testing out different methods and now has the tools and processes in place to continue sequencing locally while thinking globally. You can check out the genome notes for some of the species they have sequenced here.

In its first full year, the Generative and Synthetic Genomics programme has been hard at work, growing in size and laying the foundations for making biology programmable. Being the world’s first programme dedicated to generative biology, scientists are combining large-scale data generation and artificial intelligence to understand, predict and programme molecular biology.

This year, our researchers worked alongside collaborators at the Centre for Genomic Regulation, Barcelona to create models that predict how many different DNA changes combine to impact proteins. They uncovered that most variations acted independently, making it easier to predict their effect. By understanding the rules that determine how proteins function, Sanger scientists hope to enable more accurate diagnoses and support the design of custom proteins for drug development.

The Cellular Genetics teams have been decking the halls of the Sanger Institute with all the papers they have published this year. This programme, set up to understand the cell types in the human body, celebrated the recent publication of a bundle of more than 40 Human Cell Atlas (HCA) papers in Nature Portfolio journals.

The Human Cell Atlas, launched in 2016, is a community-led initiative that aims to harness single cell and spatial genomics technologies to map the cells of the human body. This year, the HCA reached a milestone with the publication of a collection of papers exploring a range of cellular insights from new computational methods to the composition of human organs.

As part of this bundle, Sanger scientists contributed 15 papers that have enhanced our understanding of the human body. These papers included the first blueprint of the human skeletal development that shed light on the process of arthritis, a comprehensive map of the developing human thymus, which provided insights into the immune system, and the first single-cell and spatial atlas of the human prenatal skin that could lead to clinical applications for regenerative medicine.

Our programmes don’t work in insolation: insights, ideas and techniques generated by one programme are often adapted and applied across other research teams. This collaborative approach fosters an environment for innovation and growth to deliver ambitious projects at scale.

One way that we extract maximum value from our tools, data and protocols is through the work of Informatics and Digital Solutions (IDS). The department’s infrastructure, software, hardware and data teams are constantly improving our technology workflows and horizon-scanning for new computer hardware and techniques for our scientists to use. They work directly with our research programmes and scientific operations teams to solve scientific problems together.

This year, the Sanger Institute partnered with University of Cambridge and EMBL’s European Bioinformatics Institute (EMBL-EBI) to explore the potential of quantum computing for improvements in human health. The (up to) $3.5 million project, part of the Wellcome Leap Quantum for Bio (Q4Bio) Supported Challenge Program, brings together world-leading experts in quantum computing and genomics to develop new methods and algorithms to process biological data.

Until recently, quantum computing was a pipe dream, but work done by companies such as Google and IBM are laying the foundations for real-world quantum computing chips. Unlike regular computers that use bits (0s and 1s), quantum computers use qubits, which can be 0, 1, or both at the same time. In other words, quantum computers can solve certain problems much faster than regular ones.

In this project, the team aims to use quantum computing algorithms to speed up the creation and analysis of all the different possible variation in people’s DNA around the world in one searchable supermap (known as a pangenome).

Biological research is currently in the midst of a digital transformation with new opportunities and challenges arising from advancements in artificial intelligence and data science. In the next year, the IDS department plans to invest more in this space to further push the boundaries of genomic research.

Another Christmas-stocking full of core functions at Sanger are our DNA sequencing capabilities, cell culturing, organoid generation and cellular imaging carried out by our Scientific Operations teams. Short-read, long-read, single-cell, spatial transcriptomic, you name it – our laboratories are kitted out with the latest technologies to conduct research at scale that cannot be achieved elsewhere. Our scientific operations teams are fundamental in delivering data production pipelines that enable our scientists to ask questions that others cannot answer.

As a testament to their unending quest to improve, enhance and embrace new technology to speed the delivery and analysis of genomic experiments, this year the team celebrated the Institute reading more than 50 petabases of DNA. That’s fifty thousand trillion bases of DNA, the equivalent of over half a million high-quality human genomes and more than 51 million bases per second of Sanger’s existence.