A bioinformatics tool to study complex diseases by integrating different biological scales

An international team led from the MELIS-UPF and the Hospital del Mar Research Institute has developed a multi-level biological network analysis tool and is making progress in the study of multiple sclerosis.

The new tool integrates information from different levels, from genes to behaviour, like Russian dolls. Photo by Didssph on Unsplash.

Some diseases are complex to study and treat because they involve different components of the human body at different levels: genes, cells, tissues, behaviour. This is the case, for example, with dementias, for which there is no clear marker to help diagnose and treat them. “For complex diseases, it is very difficult to have genetic biomarkers. They are often determined by several genes and there is a lot of background noise,” explains Jordi Garcia-Ojalvo, director of the Dynamic Systems Biology Lab at the Department of Medicine and Life Sciences (MELIS-UPF)

García-Ojalvo is one of the principal investigators of an international study that has developed a tool to analyse this type of disease. It is a computational tool that makes it possible to relate different biological scales, both microscopic, such as genes and cells, and macroscopic, such as tissues or behaviour. This study has been co-led by researchers at MELIS-UPF and the Hospital del Mar Research Institute.

Researchers have used this type of analysis to study multiple sclerosis, an autoimmune disease of unknown cause that affects neural tissue and causes significant disability. Some studies had already attempted to integrate biological networks to understand the disease, in particular by trying to link the effects of different genes. But never before has there been a study that links different levels. The relationship between genes, proteins, cells, tissues (using brain and retinal imaging) and behaviour was analysed in 328 patients and 90 healthy individuals.

“With this 5-level network analysis (genes, proteins, cells, organs and behaviour), we have been able to identify which elements of the different scales are related at the biological level”.
Jordi García-Ojalvo (MELIS-UPF) 

This multi-level network approach has revealed a link between the MK03 protein, previously associated with multiple sclerosis and the number of T-cells in the immune system, the thickness of the retinal nerve fibre layer and the speed at which a person can walk. This discovery is a step towards identifying a biomarker to help diagnose and treat the disease.

“In complex diseases, many things happen at the same time, at different scales and over time. It is therefore difficult for people, both researchers and doctors, to visualise what’s happening without this type of tool, which allows us to distinguish and identify the elements that are related”, says Pablo Villoslada, a researcher at the Hospital del Mar who co-led the study with García-Ojalvo. The tool they have developed can also be used to study other complex diseases, such as Alzheimer’s and other dementias.

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