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“Cardiovascular disease is the leading cause of death in Europe, responsible for 45 per cent of all deaths.”

AI used to improve cardiovascular risk prediction

AI startup Owkin and Amgen have announced the results of a three-year project using artificial intelligence to more accurately predict cardiovascular risk. This study demonstrates the ability of AI to improve the way that clinicians predict patients’ risk of suffering major cardiovascular events, such as strokes and myocardial infarctions.

Using data from 13,756 patients who were part of FOURIER, a large Amgen clinical trial, Owkin trained a machinelearning algorithm to predict those at higher risk of cardiovascular events. Published in the European Heart Journal - Digital Health, the results show that machine learning is more efficient and effective than the statistical models routinely used by clinicians. Cardiovascular disease is the leading cause of death in Europe, responsible for 45 per cent of all deaths. It represents a considerable economic burden, costing an estimated €210 billion in the European Union alone. By better predicting which patients will suffer major cardiovascular events, patient outcomes and efficiency can be drastically improved. By improving the ability to predict cardiovascular events, clinicians are better able to prevent them. Identifying at-risk patients sooner will allow them to benefit from better care, adapted to their individual risk profile. Thus, identified patients will benefit from better follow-up and therapeutic management adapted to their risk level. With electronic medical records being more complete and prevalent than ever before, the use of machine learning to better predict cardiovascular risk could have wide application. For five years, Owkin and Amgen have been collaborating on projects across cardiology, hematology and oncology to develop clinical applications for artificial intelligence. Last month, Owkin became a ‘unicorn’ – a start-up valued at over $1 billion – through a $180 million investment from Sanofi, which was announced alongside $90 million of joint cancer research projects. Jean-Frédéric Petit-Nivard, SVP Commercial & Product Strategy at Owkin, said: “We are delighted that our collaboration, which began in 2016, has yielded compelling scientific results that could fundamentally improve patient monitoring and treatment. We look forward to continuing this project with Amgen to translate these scientific findings into clinical applications.” Adrien Rousset, Head of Augmented Diagnostics at Amgen, said: “After more than three years of collaboration, we are very proud to have our results recognized and published in a prestigious scientific journal for cardiologists worldwide. We hope that this work will contribute to the next generation of tools that will help in saving more lives.” Dr. Marc S. Sabatine, the Lewis Dexter, MD Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, said: “This project has allowed us to explore the value of Machine Learning for cardiovascular risk prediction and gain important insights into the use of clinical data.”

A microscopic image of the mini stomachs used in the

research. Credit: Giovanni Giobbe

Lab-grown ‘mini-stomachs’ could shed light on children’s COVID symptoms

A ‘lab-grown model’ of the human stomach, that can be used to study how infections affect the gastrointestinal system, has been developed for the first time.

A UCL-led team of international scientists have built on recent advances to grow ‘mini-organs’ in a laboratory, known as organoids. These organoids provide researchers with invaluable tools to study how organs function both when they are healthy and when impacted by disease. The team includes Great Ormond Street Hospital (GOSH), UCL Great Ormond Street Institute of Child Health (UCL GOS ICH) and the Istituto Zooprofilattico Sperimentale delle Venezie (Legnaro, Italy). In the study, published in Nature Communications, scientists have for the first time described how to grow ministomach organoids, across differing stages of development – foetal, child and adult.

To do this, researchers, based at Zayed Centre for Research into Rare Disease in Children, isolated stem cells from patient stomach samples, and grew them under special conditions in the lab to obtain mini-stomachs in a dish that mimic the behaviour of a human stomach.

As the COVID-19 pandemic progressed, several hospitals reported gastrointestinal symptoms alongside the more usual respiratory effects like coughs and breathing difficulties, particularly in children. Following these cases, the research team, led by Dr Giovanni Giuseppe Giobbe, Professor Nicola Elvassore and Professor Paolo De Coppi from UCL GOS ICH, and Dr Francesco Bonfante from Istituto Zooprofilattico Sperimentale delle Venezie, determined that their ministomach model could be used to study how a SARS-CoV-2 infection affects the stomach.

The scientists were able to facilitate the infection of the mini-stomachs from the outside by exposing the surface of the cells to the virus. From this they showed that SARSCoV-2 could replicate within the stomach, more noticeably in organoids that were grown from the child and late foetal cells, compared to adult and early foetal cells. The research team were also able to look at the impact of the infection on the cells within the organoids, showing that a specific group of cells, called delta cells that make a hormone called somatostatin, had died, which could explain some of the stomach symptoms seen in patients. The team’s laboratory results mirror the pattern of gastrointestinal symptoms seen in patients of different ages.

Professor Paolo De Coppi, (GOSH Consultant Paediatric Surgeon and UCL GOS ICH Nuffield Professor of Paediatric Surgery), senior author said: “This study has highlighted that SARS-CoV-2 infection may begin to infect the gastrointestinal system via the stomach in children and young babies. We hope that this adds another piece to the puzzle as we try to build our understanding of the impact of the virus across the body. As a research team we are proud to have been able contribute to the global fight against coronavirus in this way, pivoting our research as the need arose.”

The team now plan to continue their work utilising these new mini-stomachs, aiming to study how the stomach develops from early in pregnancy through to adulthood. They also hope to look at the effects of other common gastrointestinal infections.

Dr Giovanni G Giobbe (UCL GOS ICH Senior Research Associate) and co-lead author on the study said: “We have been able to develop the first foetal model of the stomach and have demonstrated that the human gastric organoids can be used to accurately study real-world infections.

“Developing reliable models of organs that scientists and doctors can study in a lab are vital as they allow us to work out how organ tissue is affected during disease and infection. We want to increase our understanding of how infections impact the stomach so that we can further the search for new treatments.”

Bacteria can develop strong immunity for protection against viruses

A new study hopes to exploit newly characterised defence systems in bacteria to compare changes to the human genome.

University bioscientists have been working on the research to demonstrate the complex workings of bacterial innate immunity. Bacteria have evolved a multitude of defence systems to protect themselves from viruses called bacteriophages. Many of these systems have already been developed into useful biotechnological tools, such as for gene editing, where small changes are made to the target DNA. The researchers demonstrated that two defence systems worked in a complementary manner to protect the bacteria from bacteriophages. One system protected the bacteria from bacteriophages that did not have any modifications to their DNA. Some bacteriophages modify their DNA to avoid this first defence system. A second system, called BrxU, protected the bacteria from those bacteriophages with modified DNA, thereby providing a second layer of defence. The researchers built an extremely detailed 3-D picture of BrxU to better understand how it protects from bacteriophages with modified DNA. BrxU has the potential to be another useful biotechnological tool, because the same DNA modifications that BrxU recognises appear throughout the human genome, and alter in cancer and neurodegenerative diseases. Senior author of the study, Dr Tim Blower, an Associate Professor and Lister Institute Prize Fellow in Durham University’s Department of Biosciences, said: “Being able to recognise modified DNA is crucial, as similar modifications are found throughout the DNA of the human genome. “This extra layer of information, the “epigenome”, alters as we grow, and also changes in cases of cancer and neurodegenerative diseases. “If we can develop BrxU as a biotechnological tool for mapping this epigenome, it will transform our understanding of the adaptive information controlling our growth and disease progression.” The study findings from lead author Dr David Picton and coworkers are published in the journal Nucleic Acids Research.

Ninety-seven undergraduates, who were also involved, were in the final years of their BSc or MBiol degrees in the Department of Biosciences, Durham University.

As part of a Microbiology Workshop designed to provide research-led teaching, they were tasked with isolating new bacteriophages for study. These bacteriophages thankfully don’t harm humans, but just as the human immune system responds to infections, bacteria have been forced to evolve their own immune systems that protect from bacteriophages.

Bacteriophages were collected from the River Wear, college ponds and other waterways around Durham. They were then used to test the bacteriophage innate immunity in E. coli bacteria.

The study was led by a team of bioscientists from Durham University, UK, in collaboration with University of Liverpool, Northumbria University and New England Biolabs

Research was funded in the UK by the Biotechnology and Biological Sciences Research Council Newcastle-LiverpoolDurham Doctoral Training Partnership, the Lister Institute of Preventive Medicine, Durham University’s Biophysical Sciences Institute, and the Wellcome Trust.

Image credit: Dr Tim Blower, Durham University

“Bacteria have evolved a multitude of defence systems to protect themselves from viruses called bacteriophages.”

Ancient genes help dolphins live on

Ancient genes that predate the last Ice Age may be the key to survival … at least if you are a dolphin!

Genes up to 2.3 million years old helped the bottlenose dolphin adapt to new habitats through changes in behaviour and may be the secret to their survival and range expansion, according to the research published in Science Advances.

Understanding the processes that allow species to extend their ranges and adapt to environmental conditions in a newly available habitat, such as coastal habitats at the end of the last Ice Age, is an essential question in biology. The bottlenose dolphin is a highly social and longlived common species which has repeatedly adapted from being an offshore (pelagic) species to life in coastal waters. Key to their ability to adapt to changing environments over generations are genes associated with cognitive abilities and feeding behaviours, indicating that bottlenose dolphin sociality has helped them to adapt and survive. Dr Marie Louis, visiting scholar in Professor Oscar Gaggiotti’s research group in the School of Biology at the University of St Andrews, said: “Old genes were important contributors to bottlenose dolphins’ ability to repeatedly adapt to coastal waters across the world. “Furthermore, several of the genes involved in this repeated adaptation to coastal habitats have roles in cognitive abilities and feeding, suggesting a role of social behaviour in facilitating the ability of bottlenose dolphins to adapt to novel conditions. “Conserving old genes may thus be critical for any species to cope with current rapid global change.” The research team re-sequenced and analysed the whole genomes of 57 coastal and pelagic dolphins from three regions – the eastern North Atlantic, western North Atlantic and eastern North Pacific – to figure out how the bottlenose dolphin has been able to repeatedly adapt to coastal waters.

The team found that the pelagic and coastal ecotypes from the Atlantic and the Pacific have evolved independently, while those in the Atlantic are partially related. Scanning the genomes for patterns of genetic diversity and differentiation, the team found that some regions of the genome were under the influence of selection in all three geographically distant coastal populations and were thus likely involved in adaptation to coastal habitats. Even more striking was the fact that these genomic regions under parallel adaptation, and present at low to intermediate frequency in the pelagic populations, were very old. This suggests that these old genes have been repeatedly repackaged during the formation of coastal populations, when new coastal habitats opened up, for example at the end of the last Ice Age. The international study, led by the University of St Andrews, involved the University of Montpellier, the University of Groningen, the Norwegian University of Science and Technology, the University of Copenhagen and the University of La Rochelle in collaboration with researchers from Scotland, Ireland, the United States and Switzerland.