Computers make sense of experiments on human disease

November 12, 2008

Increased use of computers to create predictive models of human disease is likely following a workshop organised by the European Science Foundation (ESF), which urged for a collaborative effort between specialists in the field. Human disease research produces an enormous amount of data from different sources such as animal models, high throughput genetic screening of human tissue, and in vitro laboratory experiments. This data operates at different levels and scales including genes, molecules, cells, tissues and whole organs, embodying a huge amount of potentially valuable insight that current computer modelling approaches often fail to exploit properly.

However, significant advances in the modelling of a few specific diseases, such as multiple sclerosis (MS), have been made. A major aim of the ESF workshop was thus to generalise such work and create a more coherent body of expertise across the whole field of computational disease analysis, according to Albert Compte, co-convenor of the ESF workshop, from the Computational and physiological bases of cortical networks laboratory at the Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS) in Barcelona. "A workshop like this one was useful in seeing how advances in other research fields can be used more generally for disease modelling," said Compte. "So far, novel modelling approaches have been confined to a specific disease or a particular level of description".

A model might be confined just to the molecular level or the cellular level for example. The ESF workshop highlighted the benefits that could be obtained from integrating data from different levels. This can provide more detailed and flexible models, with greater power to identify causes of diseases and predict possible cures in future.

However, one potential problem when building sophisticated disease models operating at different levels is that they can become too complex, with a lack of sufficient data for any useful analysis. This can be resolved by selecting a simpler model that corresponds only to the experimental data that actually exists. Delegates at the workshop heard how in the case of MS, selection of the model could be tuned to the data, to make best use of the actual experimental results obtained in a particular study, as explained by Jesper Tegner, another co-convenor of the ESF workshop, from the Atherosclerosis Research Unit at the Karolinska Institute Centre for Molecular Medicine (CMM) in Stockholm, Sweden.

"There was one exciting presentation on MS," said Tegner. "The immune system is clearly central for MS. However, the trick in the case of MS is to represent different aspects of the immune system according to the available data.The objective isn't to model the whole immune system. One interesting level of abstraction was the presentation of agent-based modelling of MS where individual cells operated as agents, thus omitting the intracellular machinery." In other words, the detailed interior workings of the cells could be ignored in this case because that would have made the model overcomplicated, with insufficient data at the different levels to produce any useful insights.

In other experiments, data about varying levels of gene expression was obtained, which required very different models with networks of graphs. These highlighted the patterns of gene expression associated with a particular disease, such as MS.

Yet another valuable application of computer-based mathematical disease models lies in studying the phenomenon of addiction to drugs such as nicotine and helping to reconcile conflicting theories, as Compte pointed out. "The neurobiology of nicotine addiction is a hotly debated field. In particular, there are two contending views on how neurons and their connections in subcortical nuclei are affected by nicotine. This computer model allows us to reconcile the apparently contradictory results obtained from in vitro and in vivo experiments, and thus provides a single theoretical proposal of how nicotine affects neuronal circuits in the brain and causes addiction, compatible with most available experimental results."

Tegner and others at the workshop were confident that a coherent framework for building multi-level mathematical models on the basis of available data will lead to better understanding of many diseases and conditions such as drug addiction. This in turn, could lead to better therapies.

Source: European Science Foundation

Explore further: Brain modulyzer provides interactive window into the brain

Related Stories

Brain modulyzer provides interactive window into the brain

October 10, 2016

Did you know that your brain processes information in a hierarchy? As you are reading this page, the signal coming in through your eyes enters your brain through the thalamus, which organizes it. That information then goes ...

Understanding the fate of food

August 17, 2016

What exactly happens as we digest food and what are the implications for our health? Answering these questions will help design healthier foods that could curb the rising rates of obesity, diabetes and cardiovascular disease.

Saving the lives of Romanian children with HIV

August 31, 2016

Dr Paul Marinescu has chosen to meet me on a cold winter's day in a room stocked with plants, fish tanks and two parrots singing in their cages. It's a room as lively as its incumbent's life. This grey-haired man with a gentle ...

Setting standards for research into Rett syndrome

October 31, 2012

There is an urgent need for new drugs to treat Rett syndrome, a rare and severe neurological disease mainly affecting girls. A bottleneck in drug development for this syndrome is a lack of clarity at the level of preclinical ...

Recommended for you

Natural compound reduces signs of aging in healthy mice

October 27, 2016

Much of human health hinges on how well the body manufactures and uses energy. For reasons that remain unclear, cells' ability to produce energy declines with age, prompting scientists to suspect that the steady loss of efficiency ...

A metabolic switch to turn off obesity

October 27, 2016

You've tried all the diets. No matter: you've still regained the weight you lost, even though you ate well and you exercised regularly! This may be due to a particular enzyme in the brain: the alpha/beta hydrolase domain-6 ...

Mitochondria control stem cell fate

October 27, 2016

What happens in intestinal epithelial cells during a chronic illness? Basic research conducted at the Chair of Nutrition and Immunology at the Technical University of Munich (TUM) addressed this question by generating a new ...

Scientists develop 'world-first' 3-D mammary gland model

October 27, 2016

A team of researchers from Cardiff University and Monash Biomedicine Discovery Institute has succeeded in creating a three-dimensional mammary gland model that will pave the way for a better understanding of the mechanisms ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

1 / 5 (1) Nov 12, 2008
I hope the ELECTRONIC signatures are taken into account. It's a neglected ingredient in most studies, but I believe there are profound effects!

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.