Learning-accelerated discovery of immune-tumour interactions
Abstract
We present an integrated framework for enabling dynamic exploration of design spaces for cancer immunotherapies with detailed dynamical simulation models on high-performance computing resources. Our framework combines PhysiCell, an open source agent-based simulation platform for cancer and other multicellular systems, and EMEWS, an open source platform for extreme-scale model exploration. We build an agent-based model of immunosurveillance against heterogeneous tumours, which includes spatial dynamics of stochastic tumour–immune contact interactions. We implement active learning and genetic algorithms using high-performance computing workflows to adaptively sample the model parameter space and iteratively discover optimal cancer regression regions within biological and clinical constraints.
- Authors:
-
[1];
[1];
[2];
[3];
[2]
- Argonne National Lab. (ANL), Lemont, IL (United States). Decision and Infrastructure Sciences; Univ. of Chicago, Chicago, IL (United States). Consortium for Advanced Science and Engineering
- Indiana Univ., Bloomington, IN (United States). Intelligent Systems Engineering
- The Univ. of Vermont Medical Center, Burlington, VT (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- National Science Foundation (NSF); National Institutes of Health (NIH); USDOE
- OSTI Identifier:
- 1574308
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Molecular Systems Design & Engineering
- Additional Journal Information:
- Journal Volume: 4; Journal Issue: 4; Journal ID: ISSN 2058-9689
- Publisher:
- Royal Society of Chemistry
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES
Citation Formats
Ozik, Jonathan, Collier, Nicholson, Heiland, Randy, An, Gary, and Macklin, Paul. Learning-accelerated discovery of immune-tumour interactions. United States: N. p., 2019.
Web. doi:10.1039/c9me00036d.
Ozik, Jonathan, Collier, Nicholson, Heiland, Randy, An, Gary, & Macklin, Paul. Learning-accelerated discovery of immune-tumour interactions. United States. https://doi.org/10.1039/c9me00036d
Ozik, Jonathan, Collier, Nicholson, Heiland, Randy, An, Gary, and Macklin, Paul. Fri .
"Learning-accelerated discovery of immune-tumour interactions". United States. https://doi.org/10.1039/c9me00036d. https://www.osti.gov/servlets/purl/1574308.
@article{osti_1574308,
title = {Learning-accelerated discovery of immune-tumour interactions},
author = {Ozik, Jonathan and Collier, Nicholson and Heiland, Randy and An, Gary and Macklin, Paul},
abstractNote = {We present an integrated framework for enabling dynamic exploration of design spaces for cancer immunotherapies with detailed dynamical simulation models on high-performance computing resources. Our framework combines PhysiCell, an open source agent-based simulation platform for cancer and other multicellular systems, and EMEWS, an open source platform for extreme-scale model exploration. We build an agent-based model of immunosurveillance against heterogeneous tumours, which includes spatial dynamics of stochastic tumour–immune contact interactions. We implement active learning and genetic algorithms using high-performance computing workflows to adaptively sample the model parameter space and iteratively discover optimal cancer regression regions within biological and clinical constraints.},
doi = {10.1039/c9me00036d},
journal = {Molecular Systems Design & Engineering},
number = 4,
volume = 4,
place = {United States},
year = {Fri Jun 07 00:00:00 EDT 2019},
month = {Fri Jun 07 00:00:00 EDT 2019}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 21 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Genetically modified T cells in cancer therapy: opportunities and challenges
journal, April 2015
- Sharpe, M.; Mount, N.
- Disease Models & Mechanisms, Vol. 8, Issue 4
Mathematical Modeling in Immunotherapy of Cancer: Personalizing Clinical Trials
journal, January 2012
- Agur, Zvia; Vuk-Pavlović, Stanimir
- Molecular Therapy, Vol. 20, Issue 1
Extension of in vivo half-life of biologically active molecules by XTEN protein polymers
journal, October 2016
- Podust, Vladimir N.; Balan, Sibu; Sim, Bee-Cheng
- Journal of Controlled Release, Vol. 240
Extreme-Scale Dynamic Exploration of a Distributed Agent-Based Model With the EMEWS Framework
journal, September 2018
- Ozik, Jonathan; Collier, Nicholson T.; Wozniak, Justin M.
- IEEE Transactions on Computational Social Systems, Vol. 5, Issue 3
Evolution of intratumoral phenotypic heterogeneity: the role of trait inheritance
preprint, January 2013
- Gallaher, Jill; Anderson, Alexander R. A.
- arXiv
Characterizing the heterogeneity of tumor tissues from spatially resolved molecular measures
journal, November 2017
- Graf, John F.; Zavodszky, Maria I.
- PLOS ONE, Vol. 12, Issue 11
Mathematical and computational models of immune-receptor signalling
journal, June 2004
- Goldstein, Byron; Faeder, James R.; Hlavacek, William S.
- Nature Reviews Immunology, Vol. 4, Issue 6
Exhaustion of cytotoxic T cells during adoptive immunotherapy of virus carrier mice can be prevented by B cells or CD4+ T cells
journal, February 2002
- Hunziker, Lukas; Klenerman, Paul; Zinkernagel, Rolf M.
- European Journal of Immunology, Vol. 32, Issue 2
Addressing current challenges in cancer immunotherapy with mathematical and computational modelling
journal, June 2017
- Konstorum, Anna; Vella, Anthony T.; Adler, Adam J.
- Journal of The Royal Society Interface, Vol. 14, Issue 131
Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead
journal, October 2017
- Oiseth, Stanley J.; Aziz, Mohamed S.
- Journal of Cancer Metastasis and Treatment, Vol. 3, Issue 10
When Seeing Isn't Believing: How Math Can Guide Our Interpretation of Measurements and Experiments
journal, August 2017
- Macklin, Paul
- Cell Systems, Vol. 5, Issue 2
BioFVM: an efficient, parallelized diffusive transport solver for 3-D biological simulations
journal, December 2015
- Ghaffarizadeh, Ahmadreza; Friedman, Samuel H.; Macklin, Paul
- Bioinformatics, Vol. 32, Issue 8
Dynamic analysis of immune and cancer cell interactions at single cell level in microfluidic droplets
journal, September 2016
- Sarkar, S.; Sabhachandani, P.; Stroopinsky, D.
- Biomicrofluidics, Vol. 10, Issue 5
Proteome-Wide Measurement of Protein Half-Lives and Translation Rates in Vasopressin-Sensitive Collecting Duct Cells
journal, September 2013
- Sandoval, Pablo C.; Slentz, Dane H.; Pisitkun, Trairak
- Journal of the American Society of Nephrology, Vol. 24, Issue 11
Exploiting evolutionary principles to prolong tumor control in preclinical models of breast cancer
journal, February 2016
- Enriquez-Navas, Pedro M.; Kam, Yoonseok; Das, Tuhin
- Science Translational Medicine, Vol. 8, Issue 327
Adaptation in Natural and Artificial Systems: An Introductory Analysis with Applications to Biology, Control, and Artificial Intelligence
book, January 1992
- Holland, John H.
- The MIT Press
Mathematical modeling of intracellular signaling pathways
journal, October 2006
- Klipp, Edda; Liebermeister, Wolfram
- BMC Neuroscience, Vol. 7, Issue S1
libRoadRunner: a high performance SBML simulation and analysis library: Table 1.
journal, June 2015
- Somogyi, Endre T.; Bouteiller, Jean-Marie; Glazier, James A.
- Bioinformatics, Vol. 31, Issue 20
Classifying the evolutionary and ecological features of neoplasms
journal, September 2017
- Maley, Carlo C.; Aktipis, Athena; Graham, Trevor A.
- Nature Reviews Cancer, Vol. 17, Issue 10
Active Subspaces
book, January 2015
- Constantine, Paul G.
- Society for Industrial and Applied Mathematics
Strength in Numbers: Visualizing CTL-Mediated Killing In Vivo
journal, February 2016
- Nolz, Jeffrey C.; Hill, Ann B.
- Immunity, Vol. 44, Issue 2
T cell migration, search strategies and mechanisms
journal, February 2016
- Krummel, Matthew F.; Bartumeus, Frederic; Gérard, Audrey
- Nature Reviews Immunology, Vol. 16, Issue 3
Analysis of response rate with ANTI PD1/PD-L1 monoclonal antibodies in advanced solid tumors: a meta-analysis of randomized clinical trials
journal, January 2018
- Carretero-González, Alberto; Lora, David; Ghanem, Ismael
- Oncotarget, Vol. 9, Issue 9
Evolution of intratumoral phenotypic heterogeneity: the role of trait inheritance
journal, August 2013
- Gallaher, Jill; Anderson, Alexander R. A.
- Interface Focus, Vol. 3, Issue 4
Practical Heteroscedastic Gaussian Process Modeling for Large Simulation Experiments
journal, July 2018
- Binois, Mickaël; Gramacy, Robert B.; Ludkovski, Mike
- Journal of Computational and Graphical Statistics, Vol. 27, Issue 4
Post-translational modification of the interferon-gamma receptor alters its stability and signaling
journal, October 2017
- Londino, James D.; Gulick, Dexter L.; Lear, Travis B.
- Biochemical Journal, Vol. 474, Issue 20
PhysiBoSS: a multi-scale agent-based modelling framework integrating physical dimension and cell signalling
journal, August 2018
- Letort, Gaelle; Montagud, Arnau; Stoll, Gautier
- Bioinformatics, Vol. 35, Issue 7
The Kinematics of Cytotoxic Lymphocytes Influence Their Ability to Kill Target Cells
journal, May 2014
- Bhat, Purnima; Leggatt, Graham; Matthaei, Klaus I.
- PLoS ONE, Vol. 9, Issue 5
Decitabine and Vorinostat Cooperate To Sensitize Colon Carcinoma Cells to Fas Ligand-Induced Apoptosis In Vitro and Tumor Suppression In Vivo
journal, March 2012
- Yang, Dafeng; Torres, Christina M.; Bardhan, Kankana
- The Journal of Immunology, Vol. 188, Issue 9
In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity
journal, February 2016
- Halle, Stephan; Keyser, Kirsten Anja; Stahl, Felix Rolf
- Immunity, Vol. 44, Issue 2
Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
journal, October 2017
- Wolchok, Jedd D.; Chiarion-Sileni, Vanna; Gonzalez, Rene
- New England Journal of Medicine, Vol. 377, Issue 14
Hallmarks of Cancer: The Next Generation
journal, March 2011
- Hanahan, Douglas; Weinberg, Robert A.
- Cell, Vol. 144, Issue 5
Where to Go: Breaking the Symmetry in Cell Motility
journal, May 2016
- Huang, Sui
- PLOS Biology, Vol. 14, Issue 5
Dynamic analysis of immune and cancer cell interactions at single cell level in microfluidic droplets
journal, September 2016
- Sarkar, S.; Sabhachandani, P.; Stroopinsky, D.
- Biomicrofluidics, Vol. 10, Issue 5
A Review of Cell-Based Computational Modeling in Cancer Biology
journal, November 2019
- Metzcar, John; Wang, Yafei; Heiland, Randy
- JCO Clinical Cancer Informatics, Issue 3
Cancer immunotherapy in clinical practice��the past, present, and future
journal, September 2014
- Goel, Gaurav; Sun, Weijing
- Chinese Journal of Cancer, Vol. 33, Issue 9
Evolution of intratumoral phenotypic heterogeneity: the role of trait inheritance
preprint, January 2013
- Gallaher, Jill; Anderson, Alexander R. A.
- arXiv
Mathematical Modeling in Immunotherapy of Cancer: Personalizing Clinical Trials
journal, January 2012
- Agur, Zvia; Vuk-Pavlović, Stanimir
- Molecular Therapy, Vol. 20, Issue 1
Hallmarks of Cancer: The Next Generation
journal, March 2011
- Hanahan, Douglas; Weinberg, Robert A.
- Cell, Vol. 144, Issue 5
Staging the Tumor and Staging the Host: Pretreatment Combined Neutrophil Lymphocyte Ratio and Modified Glasgow Prognostic Score Is Associated with Overall Survival in Patients with Esophagogastric Cancers Undergoing Treatment with Curative Intent
journal, September 2020
- McSorley, Stephen T.; Lau, Hiu Y. N.; McIntosh, David
- Annals of Surgical Oncology, Vol. 28, Issue 2
Analysis of response rate with ANTI PD1/PD-L1 monoclonal antibodies in advanced solid tumors: a meta-analysis of randomized clinical trials
journal, January 2018
- Carretero-González, Alberto; Lora, David; Ghanem, Ismael
- Oncotarget, Vol. 9, Issue 9
Optimizing Cancer Treatment Using Game Theory: A Review
journal, January 2019
- Stanková, Katerina; Brown, Joel S.; Dalton, William S.
- JAMA Oncology, Vol. 5, Issue 1
The Kinematics of Cytotoxic Lymphocytes Influence Their Ability to Kill Target Cells
journal, May 2014
- Bhat, Purnima; Leggatt, Graham; Matthaei, Klaus I.
- PLoS ONE, Vol. 9, Issue 5
PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems
journal, February 2018
- Ghaffarizadeh, Ahmadreza; Heiland, Randy; Friedman, Samuel H.
- PLOS Computational Biology, Vol. 14, Issue 2
miRNALoc: predicting miRNA subcellular localizations based on principal component scores of physico-chemical properties and pseudo compositions of di-nucleotides
journal, September 2020
- Meher, Prabina Kumar; Satpathy, Subhrajit; Rao, Atmakuri Ramakrishna
- Scientific Reports, Vol. 10, Issue 1
Exascale design space exploration and co-design
journal, January 2014
- Dosanjh, S. S.; Barrett, R. F.; Doerfler, D. W.
- Future Generation Computer Systems, Vol. 30
Self-Generated Chemoattractant Gradients: Attractant Depletion Extends the Range and Robustness of Chemotaxis
journal, March 2016
- Tweedy, Luke; Knecht, David A.; Mackay, Gillian M.
- PLOS Biology, Vol. 14, Issue 3
Closing the Scientific Loop: Bridging Correlation and Causality in the Petaflop Age
journal, July 2010
- An, G.
- Science Translational Medicine, Vol. 2, Issue 41
The Three Es of Cancer Immunoediting
journal, April 2004
- Dunn, Gavin P.; Old, Lloyd J.; Schreiber, Robert D.
- Annual Review of Immunology, Vol. 22, Issue 1
Treating Cancer by Targeting the Immune System
journal, August 2010
- Hwu, Patrick
- New England Journal of Medicine, Vol. 363, Issue 8
Natural Innate and Adaptive Immunity to Cancer
journal, April 2011
- Vesely, Matthew D.; Kershaw, Michael H.; Schreiber, Robert D.
- Annual Review of Immunology, Vol. 29, Issue 1
Characterizing the heterogeneity of tumor tissues from spatially resolved molecular measures
journal, November 2017
- Graf, John F.; Zavodszky, Maria I.
- PLOS ONE, Vol. 12, Issue 11
Mathematical and computational models of immune-receptor signalling
journal, June 2004
- Goldstein, Byron; Faeder, James R.; Hlavacek, William S.
- Nature Reviews Immunology, Vol. 4, Issue 6
Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment
journal, January 2019
- Norton, Kerri-Ann; Gong, Chang; Jamalian, Samira
- Processes, Vol. 7, Issue 1
libRoadRunner: a high performance SBML simulation and analysis library: Table 1.
journal, June 2015
- Somogyi, Endre T.; Bouteiller, Jean-Marie; Glazier, James A.
- Bioinformatics, Vol. 31, Issue 20
High-throughput cancer hypothesis testing with an integrated PhysiCell-EMEWS workflow
journal, December 2018
- Ozik, Jonathan; Collier, Nicholson; Wozniak, Justin M.
- BMC Bioinformatics, Vol. 19, Issue S18
Abstract 611: PD-1-based combination immunotherapy reinvigorates CD8 + T cells in metastatic pancreatic cancer patients with improved survival
conference, July 2018
- Wu, Annie A.; Tsujikawa, Takahiro; Choe, Gina
- Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL, Immunology
Three-year overall survival for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001.
journal, May 2016
- Robert, Caroline; Ribas, Antoni; Hamid, Omid
- Journal of Clinical Oncology, Vol. 34, Issue 15_suppl
Tumor–stroma interactions
journal, February 2005
- Bhowmick, Neil A.; Moses, Harold L.
- Current Opinion in Genetics & Development, Vol. 15, Issue 1
xml2jupyter: Mapping parameters between XML and Jupyter widgets
journal, July 2019
- Heiland, Randy; Mishler, Daniel; Zhang, Tyler
- Journal of Open Source Software, Vol. 4, Issue 39
Decitabine and Vorinostat Cooperate To Sensitize Colon Carcinoma Cells to Fas Ligand-Induced Apoptosis In Vitro and Tumor Suppression In Vivo
journal, March 2012
- Yang, Dafeng; Torres, Christina M.; Bardhan, Kankana
- The Journal of Immunology, Vol. 188, Issue 9
Mathematical Modeling and Parameter Estimation of Intracellular Signaling Pathway: Application to LPS-induced NFκB Activation and TNFα Production in Macrophages
journal, February 2018
- Lee, Dongheon; Ding, Yufang; Jayaraman, Arul
- Processes, Vol. 6, Issue 3
Dimensional and temporal controls of three-dimensional cell migration by zyxin and binding partners
journal, January 2012
- Fraley, Stephanie I.; Feng, Yunfeng; Giri, Anjil
- Nature Communications, Vol. 3, Issue 1
T cell migration, search strategies and mechanisms
journal, February 2016
- Krummel, Matthew F.; Bartumeus, Frederic; Gérard, Audrey
- Nature Reviews Immunology, Vol. 16, Issue 3
Dimensional and temporal controls of three-dimensional cell migration by zyxin and binding partners
journal, January 2012
- Fraley, Stephanie I.; Feng, Yunfeng; Giri, Anjil
- Nature Communications, Vol. 3, Issue 1
Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment
journal, January 2019
- Norton, Kerri-Ann; Gong, Chang; Jamalian, Samira
- Processes, Vol. 7, Issue 1
BioFVM: an efficient, parallelized diffusive transport solver for 3-D biological simulations
journal, December 2015
- Ghaffarizadeh, Ahmadreza; Friedman, Samuel H.; Macklin, Paul
- Bioinformatics, Vol. 32, Issue 8
Parallel agent-based simulation with Repast for High Performance Computing
journal, November 2012
- Collier, Nicholson; North, Michael
- SIMULATION, Vol. 89, Issue 10
Exascale Computing Technology Challenges
book, January 2010
- Shalf, John; Dosanjh, Sudip; Morrison, John
- Lecture Notes in Computer Science
Natural Innate and Adaptive Immunity to Cancer
journal, April 2011
- Vesely, Matthew D.; Kershaw, Michael H.; Schreiber, Robert D.
- Annual Review of Immunology, Vol. 29, Issue 1
Rethinking Hardware-Software Codesign for Exascale Systems
journal, November 2011
- Shalf, John; Quinlan, Dan; Janssen, Curtis
- Computer, Vol. 44, Issue 11
Tumour surveillance: Missing peptides and MHC molecules
journal, February 1998
- Khanna, Rajiv
- Immunology and Cell Biology, Vol. 76, Issue 1
The Three Es of Cancer Immunoediting
journal, April 2004
- Dunn, Gavin P.; Old, Lloyd J.; Schreiber, Robert D.
- Annual Review of Immunology, Vol. 22, Issue 1
Addressing current challenges in cancer immunotherapy with mathematical and computational modeling
text, January 2017
- Konstorum, Anna; Vella, Anthony T.; Adler, Adam J.
- arXiv
Introduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation
journal, May 2008
- An, Gary
- Theoretical Biology and Medical Modelling, Vol. 5, Issue 1
Nonlinear modelling of cancer: bridging the gap between cells and tumours
journal, December 2009
- Lowengrub, J. S.; Frieboes, H. B.; Jin, F.
- Nonlinearity, Vol. 23, Issue 1
Cancer immunotherapy in clinical practice��the past, present, and future
journal, September 2014
- Goel, Gaurav; Sun, Weijing
- Chinese Journal of Cancer, Vol. 33, Issue 9
Works referencing / citing this record:
Utilizing Differential Evolution into optimizing targeted cancer treatments
preprint, January 2020
- Tsompanas, Michail-Antisthenis; Bull, Larry; Adamatzky, Andrew
- arXiv
Evolving Nano Particle Cancer Treatments with Multiple Particle Types
preprint, January 2020
- Tsompanas, Michail-Antisthenis; Bull, Larry; Adamatzky, Andrew
- arXiv
Key challenges facing data-driven multicellular systems biology
text, January 2018
- Macklin, Paul
- arXiv
Key challenges facing data-driven multicellular systems biology
text, January 2018
- Macklin, Paul
- arXiv
Key challenges facing data-driven multicellular systems biology
journal, October 2019
- Macklin, Paul
- GigaScience, Vol. 8, Issue 10
Supporting Computational Apprenticeship Through Educational and Software Infrastructure: A Case Study in a Mathematical Oncology Research Lab
journal, February 2021
- Madamanchi, Aasakiran; Thomas, Madison; Magana, Alejandra
- PRIMUS