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A case for the reuse and adaptation of mechanistic computational models to study transplant immunology.

ABSTRACT: Computational mechanistic models constitute powerful tools for summarizing our knowledge in quantitative terms, providing mechanistic understanding, and generating new hypotheses. The present review emphasizes the advantages of reusing publicly available computational models as a way to capitalize on existing knowledge, reduce the number of parameters that need to be adjusted to experimental data, and facilitate hypothesis generation. Finally, it includes a step-by-step example of the reuse and adaptation of an existing model of immune responses to tuberculosis, tumor growth, and blood pathogens, to study donor-specific antibody (DSA) responses. This review aims to illustrate the benefit of leveraging the currently available computational models in immunology to accelerate the study of alloimmune responses, and to encourage modelers to share their models to further advance our understanding of transplant immunology.

SUBMITTER: Fribourg M

PROVIDER: S-EPMC6984985 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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A case for the reuse and adaptation of mechanistic computational models to study transplant immunology.

Fribourg Miguel M

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20191023 2

Computational mechanistic models constitute powerful tools for summarizing our knowledge in quantitative terms, providing mechanistic understanding, and generating new hypotheses. The present review emphasizes the advantages of reusing publicly available computational models as a way to capitalize on existing knowledge, reduce the number of parameters that need to be adjusted to experimental data, and facilitate hypothesis generation. Finally, it includes a step-by-step example of the reuse and ...[more]

PMID: 31562790

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Project description:BackgroundLife-long immunosuppressive treatment after liver transplantation (LT) prevents graft rejection but predisposes the LT recipient to infections. Herpesvirus infections are associated with morbidity and mortality among LT recipients. Among those, especially cytomegalovirus (CMV) and varicella-zoster virus (VZV) pose challenges after LT. The aim of this study is to provide an in-depth characterization of the cellular immune response against CMV and VZV infections in LT recipients and identify potential risk factors for infection.MethodsThe Herpesvirus Infections in Solid Organ Transplant Recipients - Liver Transplant Study (HISTORY) consists of an epidemiological and immunological substudy. The epidemiological substudy is a retrospective observational cohort study that includes all patients who underwent LT in Denmark between 2010 and 2023 (N ≈ 500). Using data from nationwide hospital records and national health registries, the incidence of and clinical risk factors for CMV and VZV infections will be determined. The immunological substudy is an explorative prospective observational cohort study including patients enlisted for LT in Denmark during a 1.5-year period (N > 80). Participants will be followed with scheduled blood samples until 12 months after LT. CMV- and VZV-derived peptides will be predicted for their likelihood to be presented in participants based on their HLA type. Peptide-MHC complexes (pMHC) will be produced to isolate CMV- and VZV-specific T cells from peripheral blood mononuclear cells before and after CMV and VZV infection. Their frequency, T cell receptor sequences, and phenotypic characteristics will be examined, and in a subset of participants, CMV- and VZV-specific T cells will be expanded ex vivo.DiscussionThis study will provide novel insight into T cell immunity required for viral control of CMV and VZV and has the potential to develop a prediction model to identify LT recipients at high risk for infection based on a combination of clinical and immunological data. Furthermore, this study has the potential to provide proof-of-concept for adoptive T cell therapy against CMV and VZV. Combined, this study has the potential to reduce the burden and consequence of CMV and VZV infections and improve health and survival in LT recipients.Trial registrationClinicalTrials.gov (NCT05532540), registered 8 September 2022.

Dataset Information

A case for the reuse and adaptation of mechanistic computational models to study transplant immunology.

Publications

A case for the reuse and adaptation of mechanistic computational models to study transplant immunology.

Similar Datasets

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