Advanced mathematics gives hope for patients with Fanconi anaemia

Fanconi anaemia is a very rare genetic disease characterised by a high risk of cancer, especially squamous cell carcinoma of the oral cavity. Due to the small number of patients, it is difficult to conduct clinical trials on it. Scientists from an international team are proposing to use advanced mathematics, or more precisely, multi-level dynamic modelling, by collecting large amounts and various types of genetic and health data from a limited number of patients.

“Multi-level dynamic modelling is an advanced mathematical and computational approach used in various fields of science and engineering, which allows for analysing and explaining complex patterns,” explains Carsten Carlberg, a professor from the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences in Olsztyn, one of the authors of a publication on this topic in the journal Frontiers in Genetics.

Occurring once in 300,000 people, Fanconi anaemia is primarily caused by mutations in 22 different genes involved in repairing damaged DNA. People with Fanconi anaemia often have congenital defects. Due to gene mutations and a defect in the DNA repair process, traditional cancer treatment methods, such as chemotherapy, cannot be used for this disease.

A broad look at the data

But advanced mathematics can come to the rescue. As explained by Carlberg, mechanistic molecular modelling is a computational approach that is well suited to analysing longitudinal studies of groups of people with a limited number of participants (longitudinal studies are a way of conducting research that allows you to observe the same people repeatedly and over many years). These limitations may have various reasons: logistical, financial, or because the disease being studied, such as Fanconi anaemia (FA), is rare.

Multi-level dynamic modelling is a special case of mechanistic modelling in which a large amount of data is collected for one person and then used to create models of that person’s cells and tissues. These models are sometimes referred to as “digital twins”.

“To create and train the model, we use data from healthy and diseased tissue samples from a unique cohort of 750 patients with FA, which was built over 15 years by professor Eunike Velleuer,” explains Carlberg. “On this basis, we develop the characteristic features of squamous cell carcinoma in patients with Fanconi anaemia, which in turn allows us to develop forecasts regarding the probability of developing this cancer.” 

This approach may revolutionise the clinical treatment of people with Fanconi anaemia  says the leader of the research team, Eunike Velleuer, a professor from the University of Düsseldorf (Germany), who is one of the world’s leading experts in the field of this disease and the first author of the aforementioned publication.

The team is completed by international collaborators from Mexico and the US, who are experts in mechanistic modelling and/or Fanconi anaemia. The consortium’s ultimate goal is to create digital twins of FA patients which can be used to develop personalised treatment routes.

Using mechanistic modelling and building medical digital twins can be used far beyond the treatment of Fanconi anaemia. It could also be applied for many investigations, such as longitudinal effects of vitamin D supplementation, notes Carlberg.

Professor Carsten Carlberg is a world-famous biochemist specialising in vitamin D research. He is the leader of the scientific group dealing with nutrigenomics at the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences in Olsztyn.

More about the team’s activities at: https://welcome2.pan.olsztyn.pl/.