Abstract

Digital twins represent a key technology for precision health. Medical digital twins consist of computational models that represent the health state of individual patients over time, enabling optimal therapeutics and forecasting patient prognosis. Many health conditions involve the immune system, so it is crucial to include its key features when designing medical digital twins. The immune response is complex and varies across diseases and patients, and its modelling requires the collective expertise of the clinical, immunology, and computational modelling communities. This review outlines the initial progress on immune digital twins and the various initiatives to facilitate communication between interdisciplinary communities. We also outline the crucial aspects of an immune digital twin design and the prerequisites for its implementation in the clinic. We propose some initial use cases that could serve as “proof of concept” regarding the utility of immune digital technology, focusing on diseases with a very different immune response across spatial and temporal scales (minutes, days, months, years). Lastly, we discuss the use of digital twins in drug discovery and point out emerging challenges that the scientific community needs to collectively overcome to make immune digital twins a reality.

Details

Title
Immune digital twins for complex human pathologies: applications, limitations, and challenges
Author
Niarakis, Anna 1   VIAFID ORCID Logo  ; Laubenbacher, Reinhard 2   VIAFID ORCID Logo  ; An, Gary 3 ; Ilan, Yaron 4   VIAFID ORCID Logo  ; Fisher, Jasmin 5 ; Flobak, Åsmund 6 ; Reiche, Kristin 7 ; Rodríguez Martínez, María 8 ; Geris, Liesbet 9   VIAFID ORCID Logo  ; Ladeira, Luiz 10 ; Veschini, Lorenzo 11 ; Blinov, Michael L. 12   VIAFID ORCID Logo  ; Messina, Francesco 13 ; Fonseca, Luis L. 2   VIAFID ORCID Logo  ; Ferreira, Sandra 14 ; Montagud, Arnau 15 ; Noël, Vincent 16   VIAFID ORCID Logo  ; Marku, Malvina 17 ; Tsirvouli, Eirini 18 ; Torres, Marcella M. 19 ; Harris, Leonard A. 20   VIAFID ORCID Logo  ; Sego, T. J. 2 ; Cockrell, Chase 3   VIAFID ORCID Logo  ; Shick, Amanda E. 21 ; Balci, Hasan 22 ; Salazar, Albin 23 ; Rian, Kinza 24 ; Hemedan, Ahmed Abdelmonem 25   VIAFID ORCID Logo  ; Esteban-Medina, Marina 26 ; Staumont, Bernard 10 ; Hernandez-Vargas, Esteban 27 ; Martis B, Shiny 28 ; Madrid-Valiente, Alejandro 29 ; Karampelesis, Panagiotis 30 ; Sordo Vieira, Luis 2 ; Harlapur, Pradyumna 31   VIAFID ORCID Logo  ; Kulesza, Alexander 28 ; Nikaein, Niloofar 32 ; Garira, Winston 33 ; Malik Sheriff, Rahuman S. 34   VIAFID ORCID Logo  ; Thakar, Juilee 35   VIAFID ORCID Logo  ; Tran, Van Du T. 36   VIAFID ORCID Logo  ; Carbonell-Caballero, Jose 29 ; Safaei, Soroush 37 ; Valencia, Alfonso 38   VIAFID ORCID Logo  ; Zinovyev, Andrei 39 ; Glazier, James A. 40 

1  CNRS, Molecular, Cellular and Developmental Biology Unit (MCD), Centre de Biologie Integrative (CBI), University of Toulouse, UPS, Toulouse, France (GRID:grid.4444.0) (ISNI:0000 0001 2112 9282); Saclay-île de France, Lifeware Group, Inria, Palaiseau, France (GRID:grid.5328.c) (ISNI:0000 0001 2186 3954) 
2  University of Florida, Department of Medicine, Gainesville, USA (GRID:grid.15276.37) (ISNI:0000 0004 1936 8091) 
3  University of Vermont Larner College of Medicine, Department of Surgery, Vermont, USA (GRID:grid.59062.38) (ISNI:0000 0004 1936 7689) 
4  Hadassah Medical Center, Faculty of Medicine Hebrew University, Jerusalem, Israel (GRID:grid.17788.31) (ISNI:0000 0001 2221 2926) 
5  72 Huntley Street, UCL Cancer Institute, University College London, Paul O’Gorman Building, London, UK (GRID:grid.83440.3b) (ISNI:0000 0001 2190 1201) 
6  Norwegian University of Science and Technology, Department of Clinical and Molecular Medicine, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); St Olav’s University Hospital, The Cancer Clinic, Trondheim, Norway (GRID:grid.52522.32) (ISNI:0000 0004 0627 3560); SINTEF Industry, Department of Biotechnology and Nanomedicine, Trondheim, Norway (GRID:grid.52522.32) 
7  Fraunhofer Institute for Cell Therapy and Immunology, Department of Diagnostics, Leipzig, Germany (GRID:grid.418008.5) (ISNI:0000 0004 0494 3022); University of Leipzig, Institute of Clinical Immunology, Medical Faculty, University Hospital, Leipzig, Germany (GRID:grid.9647.c) (ISNI:0000 0004 7669 9786); Center for Scalable Data Analytics and Artificial Intelligence (ScaDS.AI), Dresden/Leipzig, Germany (GRID:grid.9647.c) 
8  Yale School of Medicine, Department of Biomedical Informatics & Data Science, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710) 
9  KU Leuven, Prometheus Division of Skeletal Tissue Engineering, Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884); KU Leuven, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884); University of Liège, Biomechanics Research Unit, GIGA Molecular and Computational Biology, Liège, Belgium (GRID:grid.4861.b) (ISNI:0000 0001 0805 7253) 
10  University of Liège, Biomechanics Research Unit, GIGA Molecular and Computational Biology, Liège, Belgium (GRID:grid.4861.b) (ISNI:0000 0001 0805 7253) 
11  King’s College London, Faculty of Dentistry Oral & Craniofacial Sciences, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764); Bloomington, Biocomplexity Institute and Department of Intelligent Systems Engineering, Indiana University, Indiana, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X) 
12  UConn Health, Center for Cell Analysis and Modeling, Farmington, USA (GRID:grid.208078.5) (ISNI:0000 0004 1937 0394) 
13  National Institute for Infectious Diseases ‘Lazzaro Spallanzani’ - I.R.C.C.S., Department of Epidemiology, Preclinical Research and Advanced Diagnostic, Rome, Italy (GRID:grid.419423.9) (ISNI:0000 0004 1760 4142) 
14  University of Beira Interior, Mathematics Department and Center of Mathematics, Covilhã, Portugal (GRID:grid.7427.6) (ISNI:0000 0001 2220 7094) 
15  Barcelona Supercomputing Center (BSC), Barcelone, Spain (GRID:grid.10097.3f) (ISNI:0000 0004 0387 1602); CSIC-UV, Institute for Integrative Systems Biology (I2SysBio), Valencia, Spain (GRID:grid.507638.f) 
16  Université PSL, Institut Curie, Paris, France (GRID:grid.440907.e) (ISNI:0000 0004 1784 3645); U900, INSERM, Paris, France (GRID:grid.7429.8) (ISNI:0000 0001 2186 6389); Université PSL, Mines ParisTech, Paris, France (GRID:grid.440907.e) (ISNI:0000 0004 1784 3645) 
17  Centre de Recherches en Cancérologie de Toulouse, Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul Sabatier, Toulouse, France (GRID:grid.468186.5) 
18  Norwegian University of Science and Technology, Department of Clinical and Molecular Medicine, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); Norwegian University of Science and Technology, Department of Biology, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393) 
19  University of Richmond, Department of Mathematics and Statistics, Richmond, USA (GRID:grid.267065.0) (ISNI:0000 0000 9609 8938) 
20  University of Arkansas, Department of Biomedical Engineering, Fayetteville, USA (GRID:grid.411017.2) (ISNI:0000 0001 2151 0999); University of Arkansas, Interdisciplinary Graduate Program in Cell and Molecular Biology, Fayetteville, USA (GRID:grid.411017.2) (ISNI:0000 0001 2151 0999); University of Arkansas for Medical Sciences, Cancer Biology Program, Winthrop P. Rockefeller Cancer Institute, Little Rock, USA (GRID:grid.241054.6) (ISNI:0000 0004 4687 1637) 
21  University of Florida, Department of Mechanical and Aerospace Engineering, Gainesville, USA (GRID:grid.15276.37) (ISNI:0000 0004 1936 8091) 
22  Maastricht University, Maastricht Centre for Systems Biology (MaCSBio), Maastricht, The Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099) 
23  INRIA Paris/CNRS/École Normale Supérieure/PSL Research University, Paris, France (GRID:grid.440907.e) (ISNI:0000 0004 1784 3645) 
24  Andalusian Public Foundation Progress and Health-FPS, Andalusian Platform for Computational Medicine, Seville, Spain (GRID:grid.440907.e) 
25  Luxembourg University, Bioinformatics Core Unit, Luxembourg Centre of Systems Biomedicine LCSB, Esch-sur-Alzette, Luxembourg (GRID:grid.16008.3f) (ISNI:0000 0001 2295 9843) 
26  Andalusian Public Foundation Progress and Health-FPS, Andalusian Platform for Computational Medicine, Seville, Spain (GRID:grid.16008.3f) 
27  University of Idaho, Department of Mathematics and Statistical Science, Moscow, USA (GRID:grid.266456.5) (ISNI:0000 0001 2284 9900) 
28  Novadiscovery, Lyon, France (GRID:grid.520209.c) (ISNI:0000 0004 5998 8789) 
29  Barcelona Supercomputing Center (BSC), Barcelone, Spain (GRID:grid.10097.3f) (ISNI:0000 0004 0387 1602) 
30  University of Patras, Department of Electrical and Computer Engineering, Patras, Greece (GRID:grid.11047.33) (ISNI:0000 0004 0576 5395) 
31  Indian Institute of Science, Department of Bioengineering, Bengaluru, India (GRID:grid.464869.1) (ISNI:0000 0000 9288 3664) 
32  Örebro University, School of Medical Sciences, Faculty of Medicine and Health, Örebro, Sweden (GRID:grid.15895.30) (ISNI:0000 0001 0738 8966); Örebro University, X‐HiDE - Exploring Inflammation in Health and Disease Consortium, Örebro, Sweden (GRID:grid.15895.30) (ISNI:0000 0001 0738 8966) 
33  Multiscale Mathematical Modelling of Living Systems program (M3-LSP), Kimberley, South Africa (GRID:grid.15895.30); Sol Plaatje University, Department of Mathematical Sciences, Kimberley, South Africa (GRID:grid.449297.5) (ISNI:0000 0004 5987 0051); Private Bag X5008, Kimberley, South Africa (GRID:grid.449297.5) 
34  Hinxton, European Bioinformatics Institute, European Molecular Biology Laboratory (EMBL-EBI), Cambridge, UK (GRID:grid.225360.0) (ISNI:0000 0000 9709 7726); Imperial College London, Department of Surgery and Cancer, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
35  University of Rochester Medical Center, Department of Microbiology & Immunology and Department of Biostatistics & Computational Biology, Rochester, USA (GRID:grid.412750.5) (ISNI:0000 0004 1936 9166) 
36  SIB Swiss Institute of Bioinformatics, Vital-IT Group, Lausanne, Switzerland (GRID:grid.419765.8) (ISNI:0000 0001 2223 3006) 
37  Ghent University, Institute of Biomedical Engineering and Technology, Gent, Belgium (GRID:grid.5342.0) (ISNI:0000 0001 2069 7798); University of Auckland, Auckland Bioengineering Institute, Auckland, New Zealand (GRID:grid.9654.e) (ISNI:0000 0004 0372 3343) 
38  Barcelona Supercomputing Center (BSC), Barcelone, Spain (GRID:grid.10097.3f) (ISNI:0000 0004 0387 1602); 23 Passeig Lluís Companys, ICREA, Barcelona, Spain (GRID:grid.425902.8) (ISNI:0000 0000 9601 989X) 
39  Evotec, In silico R&D, Toulouse, France (GRID:grid.425902.8) 
40  Bloomington, Biocomplexity Institute and Department of Intelligent Systems Engineering, Indiana University, Indiana, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X) 
Pages
141
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20567189
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41540-024-00450-5
ProQuest document ID
3134413147
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.