Additional file 7 of SBMLmod: a Python-based web application and web service for efficient data integration and model simulation

S7 — TCGA sample IDs. List of TCGA sample IDs used to calculate the results presented in Fig. 2 c and d. (TXT 76 kb

Additional file 1 of SBMLmod: a Python-based web application and web service for efficient data integration and model simulation

S1 — documentation. Documentation of the usage and file formats of SBMLmod. Also available at http://sbmlmod.uit.no . (PDF 49 kb

Model scheme.

<p>a, proliferation; b, extension with second cell state species; c, complete final model (upper part: P-C-S transitions; lower part: stress induction and cell response function F).</p

Relative number MRC-5 fibroblast cells positive for cellular markers after irradiation by the doses 0, 0.5 and 20 Gy.

<p>MRC-5. a, DNA damage marker γH2AX; b, cell cycle arrest marker p21; c, cycle arrest marker p16; d, senescence marker SA-β-Gal. The experimental error in such experiments is less than ±5%.</p

Values of the parameter f₁ in the model extension.

<p>f₁ values for model extension with cell cycle arrest species. Same experimental data as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042150#pone-0042150-t001" target="_blank">Table 1</a>. For all simulations parameter r  =  r_max is set to 0.70 determined for HeLa cell growth rate and parameter f₂ to 1.</p

Fit of Eq. 1 to constant growth for HeLa (own data: green squares, fit: blue line) and rat fibroblast cells (data: blue circles [<b>53</b>], fit: red dashed line).

<p>See also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042150#pone-0042150-t001" target="_blank">Table 1</a>.</p

Simulation of MRC-5 fibroblast data.

<p>a, experimental data (circled) were fitted by model Eq. 3a–d using Eq. 4 as an expression for monotonically increasing stress γ; b, the fraction of proliferating cells P, cells showing a cell cycle arrest or a senescent phenotype (C+S) and solely the fraction of senescent cells S are shown together with the appearance of biomarkers. Biomarker values (p16, p21, SA-β-Gal and SAHF) were measured by immune-fluorescence as number of positive cells <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042150#pone.0042150-Klement1" target="_blank">[49]</a>.</p

PD curves of human fibroblasts.

<p>Model fitting of different radiation doses and experimentally derived PDs. The data were fitted using the same parameter set for all radiation doses (differing only in the applied amount of irradiation time) applying the model described by Eq. 3a–d: a, MRC-5 fibroblast, different radiation doses 0, 0.5 and 20 Gy; b, WI-38 fibroblast, radiation doses 0, 2 and 15 Gy.</p

Simulation of WI-38 fibroblast data.

<p>a, Experimental growth data (circled) were fitted by model Eq. 3a–d using Eq. 4 as an expression for monotonically increasing stress γ; b, the fraction of proliferating cells P, cells showing a cell cycle arrest or a senescent phenotype (C+S) and solely the fraction of senescent cells S are shown together with the appearance of biomarkers. Biomarker values (p16, p21, SA-β-Gal and SAHF) were measured by immune-fluorescence as number of positive cells <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042150#pone.0042150-Klement1" target="_blank">[49]</a>.</p

Constant growth, model parameter r fitted to experimental data.

<p>Experimental data from the literature (rodent species <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042150#pone.0042150-Seluanov1" target="_blank">[53]</a>) and our own data (HeLa cells).</p