New Computational Immunology Book Explains How to Study 10 Billion Immune Cells and Molecules at a Time

The complexity of the human immune response has been difficult to characterize on a “big picture” level, but researchers at the Virginia Bioinformatics Institute at Virginia Tech have written the book on how it can be done.

“Computational Immunology: Models and Tools,” explains a set of techniques that enable researchers to study immunity at an unprecedented scale: simulated immune systems with tens of billions of interacting components.

“What makes this approach so exciting is that it reveals just how time- and context-dependent our immune functions really are,” said Josep Bassaganya-Riera, the book’s editor and director of the Nutritional Immunology and Molecular Medicine Laboratory at the Virginia Bioinformatics institute. “Modeling and informatics tools that create information processing representations of immunological processes allow researchers to connect immunology to the world above the skin, testing interventions in virtual laboratories to guide human studies.”

Understanding the human immune response has posed significant challenges in characterizing adaptive behavior, co-evolution, heterogeneity, and spatial complexity at the systems level.

While incremental progress has been made by studying key components of the immune system in isolation through reductionist approaches, technical limitations prevented researchers from efficiently investigating how all these interdependent pieces work together to influence functions at the systems level.

The new book offers methods for overcoming those obstacles.

The first reference of its kind, this volume was produced through a series of collaborations between computer scientists and immunologists at the Center for Modeling Immunity to Enteric Pathogens. Established with $12M of support from the National Institute of Allergy and Infectious Diseases, this center is dedicated to developing and disseminating user-friendly models for studying the immune system.

To illustrate how these methods can be applied and refined, the book uses examples from studies modeling the body’s complicated immune response to Helicobacter pylori, a common gut bacterium carried by half the world’s population, and inflammatory bowel disease, a debilitating immune-mediated disease that afflicts over 4 million people worldwide.

“The use cases included in the book encompass our entire process for knowledge discovery from generating new hypotheses based on simulation data to testing those predictions in the lab,” said Raquel Hontecillas, a contributing author to the book and co-director of the Nutritional Immunology and Molecular Medicine Laboratory. “In one illustration, our computational hypothesis allowed us to identify a population of CX3CR1+ macrophages that may help to regulate inflammation resulting from infection or autoimmune disease.”

”Computational Immunology: Models and Tools provides valuable insights on the art of team science and how computer scientists, mathematicians, immunologists and bioinformaticians can successfully work together to build products that are greater than the sum of their parts,” said Vida Abedi, a contributing author to the book and a member of the Nutritional Immunology and Molecular Medicine Laboratory. “This book also highlights the unmet need for computational resources, and infrastructure for simulating tens of billions of immune cells.”

By developing technologies with the ability to predict how our bodies will manage disease, the book’s authors hope to accelerate the path to cures by quickly identifying leads for further study and uncovering hidden truths about how our immune system operates.

“The development and use of advanced information and communication technologies in support of lab hypothesis generation and to developing novel interventions is fundamental to the advancement of precision medicine,” said Bruno Sobral, a contributing author to the book and a professor and director at the One Health Institute, Colorado State University. “The coupling of systems of microorganisms with the mammalian immune system provides a fertile ground for such transformative innovation.”

Published Nov. 1 by Elsevier, ‘Modeling Immunity’ is now available online. This work was supported in part by National Institute of Allergy and Infectious Diseases Contract No. HHSN272201000056C to Josep Bassaganya-Riera.

The Virginia Bioinformatics Institute was established in 2000 with an emphasis on informatics of complex interacting systems scaling the microbiome to the entire globe. It helps solve challenges posed to human health, security, and sustainability. Headquartered at the Blacksburg campus, the institute occupies 154,600 square feet in research facilities, including state-of-the-art core laboratory and high-performance computing facilities, as well as research offices in the Virginia Tech Research Center in Arlington, Virginia.

About NIMML

The NIMML Institute is a 501 (c) (3) non-profit public charity foundation focused on a transdisciplinary, team-science approach to precision medicine at the interface of immunology, inflammation, and metabolism. The NIMML Institute team has led numerous large-scale transdisciplinary projects and is dedicated to solving important societal problems by combining the expertise of immunologists, computational biologists, toxicologists, modelers, translational researchers, and molecular biologists. The Institute is headquartered in Blacksburg, VA. For more information, please visit www.nimml.org or contact pio@nimml.org.