Development of a bioinformatics
platform for MS research
Recent advances in human DNA sequencing has produced an explosion in the amount of complex computer based genetic data. In order to understand and study this large scale genetic data, scientists need to develop new computer software tools. This has created a new research discipline called bioinformatics, a field that draws on expertise from computer science, statistics, mathematics, engineering and biology.
From 2013 to 2016, MS Research Australia with the full support of the Trish MS Research Foundation provided support to the ANZgene platform to enable them to carry out cutting edge bioinformatics. This grant enabled the nationwide ANZgene collaborative group to develop advanced rapid tools to analyse the invaluable genetic information previously collected. In particular they were very interested in developing tools to detect small chemical modifications to the DNA called DNA methylation. This chemical modification is a way of turning genes on and off. These studies have provided evidence that DNA methylation is important in determining a person’s risk of developing MS.
The group has also used bioinformatics to identify different types of immune cells in the blood, by their different chemical modifications or DNA methylation patterns. This would result in each subtype of cell using different genes. Success in this has meant that scientists can simply collect blood from patients, and they don’t need to physically separate out different types of cells. This means collection, storage and transport of entire blood samples, rather than individual cell populations can occur.
Using samples from 14 people without MS, they used specific bioinformatics algorithms to determine what DNA chemical modifications occurred in the different cells in the blood. They found that about 40% of the methylation signal they recorded was related to the cell type, and could be used to stratify the cells into six distinct groups. They also confirmed this result with another technique called flow cytometry, which is regularly used in hospital medical laboratories to separate cells. Current research is investigating the methylation sites in different cell subtypes and comparing the results between people with and without MS.
This grant allowed the group to secure further funding from the National Health and Medical Research Council, to follow genetic changes from people who are at risk of MS over a 15 year period. This will help determine whether there is a change in the DNA methylation pattern as a person’s MS progresses. This funding has allowed this team to build international collaborations with Associate Professor Mika Gustafsson in Sweden, and Professor Lisa Barcellos in the USA.
The tools produced from this research will be used to generate and interpret data from clinical studies that may be investigating the effect of new treatments for MS.