(T-047) FIVEDB as a tool for analysis of in vitro experimental data: cytokine production by primary cells and cell lines

Anna Kopeikina, MSc – researcher, InSysBio UK; Almina Polinova, MSc – researcher, InSysBio UK; Nail Gizzatkulov, n/a – programmer, InSysBio UK; Alexander Stepanov, MSc – researcher, InSysBio UK; Oleg Demin, PhD – researcher, InSysBio UK

Objectives: Mathematical biomodels include a lot of processes and regulatory interactions. Use of in vitro data for parameters estimation is important but time-consuming work for modelers. To facilitate searching and analysis of experimental data for model calibration we developed fIVEDB [1], which collects experimental data from literature, automatically converts them to unified units and calculates kinetic parameters describing cell death, proliferation, migration, differentiation, and secretion. Quantitative in vitro results are often obtained using immortalized cell lines because they are considered as good biological models and have some advantages: easy to use, last longer and provide a homogenous population of cells. But cell lines are genetically modified and that can alter physiological properties in case of extensive passaging. In our study we compared production of cytokines secreted by primary cells and immortalized cell lines to find out if cell lines data are suitable for model parameters estimation. Our results can help modelers choose appropriate experimental data for model calibration.

Methods: In vitro experimental data for fIVEDB are manually extracted from literature sources and translated into kinetic parameters (kbase, Emax, Imax, EC50, IC50 etc.) The parameter calculation based on equations for standard in vitro experiments developed by InSysBio [2]. For comparing of kinetic parameters for cell lines and primary cells cytokine production, we downloaded data for primary monocytes and monocytic cell lines: THP-1 and Mono-Mac-6. For each group of data for primary cells and cell lines, we performed statistical data processing using a one-sided Mann-Whitney test.

Results: A comparative analysis of pro-inflammatory cytokine production (TNFα, IL-6, IL-1β), anti-inflammatory (IL-8, IL-10), and chemokines CCL2, CCL3 was carried out between THP-1 cell line and primary monocytes obtained from healthy donors. No statistically significant differences were found in any comparison group, suggesting that THP-1 is a good alternative for modelers when the main data pool is lacking. The same analysis was performed for Mono-Mac-6, no significant differences were observed for this cell line compared to primary cells.

Conclusions: Using in vitro experimental data collected in fIVEDB we compared cytokine production by monocytic cell lines (THP-1, Mono-Mac-6) and corresponding primary cells. Performed analysis showed that there are no significant differences between calculated parameters for these cultures, so quantitative results obtained for studied cell lines (THP-1, Mono-Mac-6) can be used for estimation of biological model parameters in case of lack of primary cells data.

Citations: [1] fIVE Database. InSysBio. https://5db.insysbio.com/
[2] InSysBio Blog. InSysBio. https://insysbio.com/blog