The science behind mechanistic immune intelligence

• Modeling the connected immune system

  A mechanistic model spanning 11 disease contexts connects immune cells and secreted signals to simulate responses to infection, autoimmunity, and lung transplantation. The study evaluated its predictions in 38 validation experiments against published observations.

  11

  disease contexts

  1,450

  regulatory interactions

  38

  validation experiments

  Moore et al. · Frontiers in Immunology · 2026

  A comprehensive mechanistic multicellular model of the human immune system spanning 11 diseases

  Robert Moore, Lauren Mayo, Dennis Startsev, Bhanwar Lal Puniya, Kashish Poore, Resa Helikar, Tomáš Helikar

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• Identifying therapeutic targets

  Disease-specific metabolic models identified 68 candidate drug targets across three autoimmune diseases. In vitro experiments combined with published evidence supported CD4+ T-cell suppression for half of the identified targets.

  68

  candidate targets

  3

  autoimmune diseases

  Puniya et al. · npj Systems Biology and Applications · 2021

  Integrative computational approach identifies drug targets in CD4+ T-cell-mediated immune disorders

  Bhanwar Lal Puniya, Rada Amin, Bailee Lichter, Robert Moore, Alex Ciurej, Sydney J. Bennett, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar

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• Connecting molecular mechanisms to immune behavior

  A CD4+ T-cell model integrated signaling, metabolism, cell populations, and cytokine dynamics using four modeling approaches. It reproduced published experimental behaviors and predicted emergent immune responses arising across scales.

  4

  modeling approaches

  3

  spatial scales

  Wertheim et al. · PLOS Computational Biology · 2021

  A multi-approach and multi-scale platform to model CD4+ T cells responding to infections

  Kenneth Y. Wertheim, Bhanwar Lal Puniya, Alyssa La Fleur, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar

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Published CD4+ T-cell research has demonstrated multiscale integration. ImmuNovus is extending this approach across additional immune cell types and disease contexts.

• Connecting immune-cell signaling and communication

  A mechanistic dendritic-cell model links intracellular signaling with cell–cell communication and explores immune responses in infection and cancer contexts.

  Aghamiri et al. · Frontiers in Immunology · 2023

  A multiscale mechanistic model of human dendritic cells for in-silico investigation of immune responses and novel therapeutics discovery

  Sara Sadat Aghamiri, Bhanwar Lal Puniya, Rada Amin, Tomáš Helikar

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• Integrating multi-omics into metabolic models

  COMO provides a pipeline for integrating multi-omics data into metabolic modeling for drug-discovery research.

  Briefings in Bioinformatics · 2023

  COMO: a pipeline for multi-omics data integration in metabolic modeling and drug discovery

  Brandt Bessell, Josh Loecker, Zhongyuan Zhao, Sara Sadat Aghamiri, Sabyasachi Mohanty, Rada Amin, Tomáš Helikar, Bhanwar Lal Puniya

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Alongside original research, Helikar and collaborators have contributed roadmaps and perspectives on the development and application of mechanistic immune digital twins.

• Building digital twins of the human immune system: toward a roadmap

  npj Digital Medicine · 2022

  R. Laubenbacher, A. Niarakis, T. Helikar, G. An, B. Shapiro, R. S. Malik-Sheriff, T. J. Sego, A. Knapp, P. Macklin, J. A. Glazier

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• Toward mechanistic medical digital twins: some use cases in immunology

  Frontiers in Digital Health · 2024

  Reinhard Laubenbacher, Fred Adler, Gary An, Filippo Castiglione, Stephen Eubank, Luis L. Fonseca, James Glazier, Tomas Helikar, Marti Jett-Tilton, Denise Kirschner, Paul Macklin, Borna Mehrad, Beth Moore, Virginia Pasour, Ilya Shmulevich, Amber Smith, Isabel Voigt, Thomas E. Yankeelov, Tjalf Ziemssen

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56 publications