Generation of digital patients for the simulation of tuberculosis with UISS-TB.


Journal

BMC bioinformatics
ISSN: 1471-2105
Titre abrégé: BMC Bioinformatics
Pays: England
ID NLM: 100965194

Informations de publication

Date de publication:
14 Dec 2020
Historique:
received: 16 09 2020
accepted: 22 09 2020
entrez: 14 12 2020
pubmed: 15 12 2020
medline: 5 1 2021
Statut: epublish

Résumé

The STriTuVaD project, funded by Horizon 2020, aims to test through a Phase IIb clinical trial one of the most advanced therapeutic vaccines against tuberculosis. As part of this initiative, we have developed a strategy for generating in silico patients consistent with target population characteristics, which can then be used in combination with in vivo data on an augmented clinical trial. One of the most challenging tasks for using virtual patients is developing a methodology to reproduce biological diversity of the target population, ie, providing an appropriate strategy for generating libraries of digital patients. This has been achieved through the creation of the initial immune system repertoire in a stochastic way, and through the identification of a vector of features that combines both biological and pathophysiological parameters that personalise the digital patient to reproduce the physiology and the pathophysiology of the subject. We propose a sequential approach to sampling from the joint features population distribution in order to create a cohort of virtual patients with some specific characteristics, resembling the recruitment process for the target clinical trial, which then can be used for augmenting the information from the physical the trial to help reduce its size and duration.

Sections du résumé

BACKGROUND BACKGROUND
The STriTuVaD project, funded by Horizon 2020, aims to test through a Phase IIb clinical trial one of the most advanced therapeutic vaccines against tuberculosis. As part of this initiative, we have developed a strategy for generating in silico patients consistent with target population characteristics, which can then be used in combination with in vivo data on an augmented clinical trial.
RESULTS RESULTS
One of the most challenging tasks for using virtual patients is developing a methodology to reproduce biological diversity of the target population, ie, providing an appropriate strategy for generating libraries of digital patients. This has been achieved through the creation of the initial immune system repertoire in a stochastic way, and through the identification of a vector of features that combines both biological and pathophysiological parameters that personalise the digital patient to reproduce the physiology and the pathophysiology of the subject.
CONCLUSIONS CONCLUSIONS
We propose a sequential approach to sampling from the joint features population distribution in order to create a cohort of virtual patients with some specific characteristics, resembling the recruitment process for the target clinical trial, which then can be used for augmenting the information from the physical the trial to help reduce its size and duration.

Identifiants

pubmed: 33308156
doi: 10.1186/s12859-020-03776-z
pii: 10.1186/s12859-020-03776-z
pmc: PMC7733699
doi:

Substances chimiques

Antibodies, Bacterial 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

449

Subventions

Organisme : H2020 European Research Council
ID : 777123

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Auteurs

Miguel A Juárez (MA)

School of Mathematics and Statistics, University of Sheffield, Sheffield, S3 7RH, UK. m.juarez@sheffield.ac.uk.

Marzio Pennisi (M)

Computer Science Institute, DiSIT, University of Eastern Piedmont, Alessandria, Italy.

Giulia Russo (G)

Department of Drug Sciences, University of Catania, Catania, Italy.

Dimitrios Kiagias (D)

School of Mathematics and Statistics, University of Sheffield, Sheffield, S3 7RH, UK.

Cristina Curreli (C)

Department of Industrial Engineering, University of Bologna, Bologna, Italy.

Marco Viceconti (M)

Department of Industrial Engineering, University of Bologna, Bologna, Italy.

Francesco Pappalardo (F)

Department of Drug Sciences, University of Catania, Catania, Italy.

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Classifications MeSH