What project is currently taking up most of your time?
In February this year, we were awarded a £1.7M collaborative grant from Innovate UK for a ground-breaking project that could help develop new tests and treatments for patients with non-alcoholic fatty liver disease (NAFLD).
NAFLD is an accumulation of excess fat in the liver of people who drink little or no alcohol, and is strongly linked to type II diabetes and obesity. The progressive form of NAFLD, known as non-alcoholic steatohepatitis (NASH), can lead to liver fibrosis, liver cancer and premature death. Around 25% of the population are thought to have NAFLD, so it’s a massive issue.
To tackle the problem we need to get better at recognising the disease earlier and uncover some effective treatments, because currently there is no approved therapy.
The grant funding is being used to develop a Data Commons, known as SteatoSITE. A Data Commons is a unified data system that allows sharing of genomic and clinical information from patients with NASH, making it more accessible for further research.
SteatoSITE will be the world’s first Data Commons for NASH, and when complete it will lead to a deeper understanding of which tests and treatments are most effective for individual patients.
What stage is the project at?
We’re currently at the pilot stage. For PMS-IC, this involves preparing “libraries” from ribonucleic acid (RNA) that has been extracted from 59 samples of liver tissue from patients with NASH, which have come from the biorepositories in Glasgow and Edinburgh. These samples are a mixture of tissue taken from surgery and from fine needle biopsies.
How has this process been going?
The tissue samples we have are known as FFPE (Formalin-Fixed Paraffin-Embedded) samples – this means they are not fresh, they have been preserved. This can present some challenges as the preservation process can result in degradation of the RNA, resulting in shorter fragments than you might get from fresh tissue. Longer fragments generally give better results. Because of our expertise in working with difficult samples, we are in the process of tweaking our library process to overcome the issues associated with FFPE samples.
The samples have had a lot of analysis done on them to allow us to see how intact the RNA is – we use a metric called DV200, which tells us the percentage of fragments which are less than 200 bases in length, as we know we won’t get great results from these. The best samples have about 70% of their RNA fragments above 200 bases in length. Anything with less than 30% of fragments above 200 bases in length is likely to be too degraded to be useful.
What will this pilot study achieve?
The pilot study will help us set our acceptance criteria for samples for the overall project. If we know that samples that have a certain level of degradation don’t produce good libraries, then it’s a waste of time including them. However, we want as many libraries as possible to make sure the cohort for the overall study is as big as it can be. The good news is that most of the samples in the pilot are giving us good yields, which is really encouraging.
What’s next for the project?
We will transport the pilot libraries to Edinburgh Genomics, who are a global leader in DNA sequencing and genomics based at the University of Edinburgh. They will carry out the sequencing part of the project – this is where they will look at the genomic information in each of the samples.
Once they’ve done that, we’ll then get feedback on the quality of the sequencing, which will tell us if we’re ready to get started on the full-blown project, which will consist of 1000 tissue samples. There will be a lot of data to come out of that! This new data will be combined with information from digital pathology, clinical and electronic health records. It will help to pinpoint patients at high risk of disease progression and will speed up the development of new therapies.
What strengths are PMS-IC bringing to this project?
Firstly, we can access ethically sourced tissue samples from biorepositories right across Scotland. We have capabilities to prepare libraries which are suitable for sequencing, including working successfully with degraded FFPE samples. We can also build successful relationships and collaborations with world-class teams such as Edinburgh Genomics.
If you think we could work on a project together, please get in touch with us on firstname.lastname@example.org