Modeling-Enabled Precision Medicine and Health Thrust at Virginia Tech

Diabetes. Inflammatory Bowel Disease (IBD). Clostridium difficile-associated disease. These and a host of other diseases and syndromes have become increasingly difficult to treat using conventional methods that do not take into account individual genetic, environmental, and lifestyle differences. The “one-size-fits-all” approach to healthcare no longer works. More and more, we are faced with the challenge of learning how to treat the individual, as opposed to using broad-spectrum therapies or treatments that respond only to a subset of the population. The Nutritional Immunology and Molecular Medicine Laboratory at Virginia Tech (NIMML) Precision Medicine and Health Thrust is developing computational tools to accelerate research in responses to diseases at the individual level. Researchers and clinicians are joining forces in leveraging the power of these computational technologies to find new ways of addressing these challenges.

The Precision Medicine Initiative, backed in 2015 by President Obama, seeks to bring together a cohort of people across the country from all walks of life to participate in a groundbreaking study that will move precision medicine forward. As the President noted, “…[P]recision medicine…is not just giving researchers and medical practitioners tools to cure people, it is also empowering individuals to monitor and take a more active role in their own health.”

Nutritional immunology has, up until this point, focused mostly on the role of nutrition in overall well-being and health. Due to many technological challenges, researchers were unable until now to investigate nutrition from the perspective of massively- and dynamically-interacting systems. Today, with computational modeling and immunoinformatics infrastructures, we can study health and disease at the interface of food, microbiome, metabolism, and the immune system. The National Microbiome Initiative is an attempt to better understand and restore dysfunctional microbiomes, which can cause health problems. Dissecting nutritional, immune and environmental effects on the Gut Microbiome will have a significant impact on health at many scales including a direct effect on the central nervous system.

“The ability to seamlessly integrate big data and theory across complex information processing architectures offers unforeseen opportunities to transform the precision medicine, health and wellness paradigm into an asset to improve the healthcare delivery systems in the U.S. and worldwide” said Josep Bassaganya-Riera, Director of the Nutritional Immunology and Molecular Medicine Laboratory (NIMML) at the Biocomplexity Institute.

In an article in Frontiers in Nutrition, NIMML researchers discuss how modeling-enabled systems nutritional immunology may be able to help us find the answers to some of the immunology’s most pressing questions underlying mechanisms of action at the interface of microbiome, nutrition and immunity.

More and more, we are finding unique links between immunology and nutrition in ways we could not have done a decade ago. For instance, NIMML scientists have seen that the absence of H. pylori in the gut may be implicated in diabetes and obesity, and there are results from other studies to suggest that the gut microbiome and changes in glucose metabolism may have an important role to play in Neurodegenerative diseases such as Parkinson’s disease, and Alzheimer’s disease.

The connection between immunology and nutrition is not surprising when we consider that there are 100 trillion microbes in the gut that help regulate the immune system and interact with brain function in complex ways. Our microbiome is constantly changing in response to nutrition, environment, and time. Dysregulation and instability can cause diseases and disorders from Inflammatory Bowel Disease (IBD) to obesity and asthma.

To deepen our understanding of how all of these systems intertwine, we use an array of high-throughput technologies and high performance computing as well as computational modeling. The NIH/NIAID Center for Modeling Immunity to Enteric Pathogens (MIEP) at Virginia Tech is a $12 million project that uses modeling computational approaches to study mucosal immune responses to infectious disease. Such a systematic effort aimed at creating data-driven and mechanistic computer models, generating novel hypotheses through synergisms with computational simulations, and experimentally validating the mechanisms of immunoregulation underlying mucosal immune responses holds enormous potential for discovering unforeseen targets and novel therapeutics for infectious and immune-mediated diseases. The project makes use of NIMML’s novel high-performance computing (HPC)-driven modeling software, ENISI, which allows us to a three-dimensional real-time glimpse into the inner workings of the immune system and its interaction with commensal or pathogenic bacteria.

The MIEP models have recently been highlighted as the Model of the Month on the BioModels Database, and were also featured in the Stanford Biomedical Computation Review article “Computing the Gut.” Future articles on the hybrid career paths of immunologists interested in computational modeling are forthcoming.

“NIMML’s modeling infrastructure enables the study of immunity at an unprecedented scale and speed by simulating signaling pathways, immune responses, metabolic networks, cytokine diffusions, cell movements and tissue-level lesion formation with trillions of interacting components at the gut mucosa, and integrating spatiotemporal scales spanning from nanoseconds to years, from molecules to cells, and into synthetic patient populations and clinical cohorts.” Said Josep Bassaganya-Riera, Director of NIMML. “These open source computational capabilities have applications both in fundamental immunology research and accelerating the development of new nutritional and pharmaceutical products for widespread and debilitating diseases. BioTherapeutics, a Virginia Tech spin-off Company, is an example of synergistically combining modeling and experimentation to advance the development of new products for glycemic control, immune health, gut health, and IBD”.