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Unified approach for in vitro data based parameters estimation
EP37246
Poster Title: Unified approach for in vitro data based parameters estimation
Submitted on 12 May 2021
Author(s): Veronika Musatova, Oleg Demin, Svetlana Rubina
Affiliations: InSysBio LLC, Moscow
This poster was presented at ACoP11
Poster Views: 185
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Poster Information
Abstract: Objectives:
The main aim of this study is to develop a unified approach to parameters estimation from the in vitro data and its
implementation in an upgrade of the Immune Response Template (IRT) - platform describing the interaction of
different types of immune cells, cytokines and facilitating the development new immunotherapies and their
combinations.
Methods:
Immune Response Template (IRT) is QSP platform of the immune system and a tool for the development of QSP
and mechanistic models related to immune response. The core of IRT is an ordinary differential equations-based
model, which includes a description of immune cells cycle processes, cytokines secretion and surface molecules
interaction. Model parameters may be assessed from the in vitro data, obtained in experiments with typical design
for cells survival, proliferation, migration or secretion studies. We developed 6 mathematical models describing
typical in vitro experiments to derive formulas allowing direct parameters calculation from the in vitro data
assessing apoptosis, proliferation, migration, differentiation and cytokine synthesis by immune cells.
Results:
Typical in vitro experiments were modeled, and processes were described using a mathematical approach to account
for multiple cytokines regulatory impact on cell processes [1]. Derived formulas allow direct calculation of
parameters from the in vitro data, resulting in a reduction of a model development time. The example of parameter
calculation is shown on the figure 1. Developed formulas were used in parameter identification for IRT version 3
and 3.1, allowing the calculation of nearly 950 parameters directly from the in vitro data without additional models
development and fitting.
Summary: An approach to processes description, accounting multiple regulators impact [1], together with developed
derivations for typical in vitro experiments studying cell proliferation apoptosis, migration and cytokines secretion
allowed the significant increase of identified parameters number in the IRT platform version 3.1 as compared to the
IRT version 2.1
References: 1. Mechanistic approach to describe multiple effects of regulatory molecules on cell dynamics process in
immune response. Oleg Demin, Evgeny Metelkin, Galina Lebedeva, Sergey Smirnov, ACoP7, Bellevue,
WA, US.
2. Dieu-Nosjean MC, Massacrier C, Homey B, et al. Macrophage inflammatory protein 3alpha is expressed at
inflamed epithelial surfaces and is the most potent chemokine known in attracting Langerhans cell
precursors. J Exp Med. 2000;192(5):705‐718. doi:10.1084/jem.192.5.705
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