DataSheet1_Agent-based models in cellular systems.pdf

This mini-review discusses agent-based models as modeling techniques for studying pattern formation of multi-cellular systems in biology. We introduce and compare different agent-based model frameworks with respect to spatial representation, microenvironment, intracellular and extracellular reactions, cellular properties, implementation, and practical use. The guiding criteria for the considered selection of agent-based model frameworks are that they are actively maintained, well documented, and provide a model development workflow.</p

Presentation_1_Comparative expression analysis in three Brassicaceae species revealed compensatory changes of the underlying gene regulatory network.pdf

Trichomes are regularly distributed on the leaves of Arabidopsis thaliana. The gene regulatory network underlying trichome patterning involves more than 15 genes. However, it is possible to explain patterning with only five components. This raises the questions about the function of the additional components and the identification of the core network. In this study, we compare the relative expression of all patterning genes in A. thaliana, A. alpina and C. hirsuta by qPCR analysis and use mathematical modelling to determine the relative importance of patterning genes. As the involved proteins exhibit evolutionary conserved differential complex formation, we reasoned that the genes belonging to the core network should exhibit similar expression ratios in different species. However, we find several striking differences of the relative expression levels. Our analysis of how the network can cope with such differences revealed relevant parameters that we use to predict the relevant molecular adaptations in the three species.</p

Extension of L1 signal beyond the first three cell layers.

<p>The white bar in the figures show the distance at which the concentration of the L1 signal drops to 10% of its initial concentration (A) CLV3 expression in wt. (B) CLV3 expression resulting from the extended L1 signal. the CLV3 mRNA expression extends to organizing center. This has never been observed experimentally in the wildtype SAM, hence the model predict that L1 signal is confined to the upper three cell layers. For examples of models out put in an uncropped template see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0147830#pone.0147830.s002" target="_blank">S2 Fig</a>.</p

Additional file 1 of Designing synthetic networks in silico: a generalised evolutionary algorithm approach

Supplementary Information. Contains: Implementation of EA algorithm; details regarding the simulations tests performed in the main text; mathematical descriptions of the scoring functions used in optimisation; multi-objective analysis of feed-forward loops; supplementary figures & tables. (PDF 614 kb

The effect of the <i>clv3</i> mutation on WUS expression.

<p>Green shows the extent of WUS expression in wildtype, and red shows WUS expression in the clv3 mutant. The expression zones are defined as cells that express WUS at the half maximum level of expression in the mutant or higher. In the mutant the concentration of WUS increases, this means the number of cells that express WUS at a high enough level to be considered within the expression zone, increases. For examples of models out put in an uncropped template see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0147830#pone.0147830.s002" target="_blank">S2 Fig</a>.</p

DataSheet_1_Quantitative analysis of MBW complex formation in the context of trichome patterning.pdf

Trichome patterning in Arabidopsis is regulated by R2R3MYB, bHLH and WDR (MBW) genes. These are considered to form a trimeric MBW protein complex that promotes trichome formation. The MBW proteins are engaged in a regulatory network to select trichome cells among epidermal cells through R3MYB proteins that can move between cells and repress the MBW complex by competitive binding with the R2R3MYB to the bHLHL protein. We use quantitative pull-down assays to determine the relative dissociation constants for the protein-protein interactions of the involved genes. We find similar binding strength between the trichome promoting genes and weaker binding of the R3MYB inhibitors. We used the dissociation constants to calculate the relative percentage of all possible complex combinations and found surprisingly low fractions of those complexes that are typically considered to be relevant for the regulation events. Finally, we predict an increased robustness in patterning as a consequence of higher ordered complexes mediated by GL3 dimerization.</p

Wildtype expression pattern of the molecules in the model.

<p>The relative levels in each figure are depicted by a color spectrum shown by the color bar in the figure. For examples of models out put in an uncropped template see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0147830#pone.0147830.s002" target="_blank">S2 Fig</a>.</p

CK lifetime as a function of <i>D</i>_<i>eff</i> and <i>n</i>₀.

<p>The average lifetime <i>τ</i> of CK in minutes in the meristem and the extension <i>n</i>₀ in cell layers of the CK synthesis zone consistent with the observation of a CK profile covering the upper 25 cell layers of the meristem. The colorbar shows the chosen value of the effective diffusion constant of CK in the meristemic tissue, ranging from 42<i>μm</i>² <i>s</i>⁻¹ to 241<i>μm</i>² <i>s</i>⁻¹ (see text).</p

Two coupled sub-networks and boundary information define WUS and CLV3 expression domains in the SAM.

<p><i>A</i> and <i>B</i> stand for type-b and type-A ARRs. <i>A</i>_<i>p</i> and <i>B</i>_<i>p</i> denote phosphorylated type-B and type-B ARRs. (A) The model can be divided into the CK signaling (blue) and WUS/CLV3 (green) sub-networks combined with boundary morphogens (L1 and CK). The former determines the position of the WUS domain via a self-organizing system while the latter specifies the CLV3 domain, taking the WUS domain as an input. The network consists of interactions and molecules that are based on published experimental data (black arrows and letters) and hypothetical interactions and molecules (red arrows and letters). Parts of the CK signaling sub-network correspond to the components of the (B) classical activator/inhibitor system; (C) the network component corresponding to the autocatalytic activator and (D) to the activation/inhibition interactions.</p

WUS and CLV3 expression patterns after <i>in silico</i> ablation.

<p>(A) and (C): the wildtype expression pattern of WUS and CLV3. (B) and (D): WUS and CLV3 expression patterns that form after ablation of the center of the SAM including the SCD and OC. For examples of models out put in an uncropped template see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0147830#pone.0147830.s002" target="_blank">S2 Fig</a>.</p