###Anonymous Review 3 and Authors Response _**Impact: ** As far as I can judge the proposal is ambitious and aims at a fundamental question. _ _**Feasibility: ** See comments below re evaluation. _ _**Overall evaluation:** The proposal addresses a fascinating problem. It proposes a set of experiments (detecting glycoconjugate residues on cell surface) driven by theory and simulations. The modelling approach has interesting methodological component based on hidden-state models for spatial distribution._ _Two main concerns about components of the proposal that should be thought out more deeply._ _(1) It is not clear how the parameters of the models will be determined. Will they be learned/estimated from data? (how?) or estimated based on prior/other experiments? or searched for and then compared to collected data?_ **Response:** The preliminarily idea (which is in real work always subject to reevaluation and to change) is that the predictions on the parameters (e.g. the boundary conditions) will be given by a theoretical search in the frame of the mathematical part. Afterwards, during the sets of suggested experiments, the real values of parameters will be found inside the predicted intervals. _(2) Experimental validation. The results of Figure 3 are impressive. I am concerned about the lack of clear quantitative methodology to compare simulations results with the collected data._ **Response:** Correct. We are working on it. _ One issue for example is that in this setup, due to the large number of analyzed cells, the statistical problem of multiple comparisons is challenging, it may be easy to find patterns that "look similar" but are not discriminative enough about the model._ **Response:** In our theoretical mathematical part which was not presented in the proposal due to the limited size, we pay a lot of attention to this problem. Namely, we suggest to use a metric for the comparisons of two objects (organisms) by using Gromov-Hausdorff type distance.

###Anonymous Review 2 and Authors Response _ **Impact: ** If successful, the project would lead to better understanding of cell development and differentiation process, and potentially to the elucidation of new "laws" governing morphogenesis._ _**Feasibility: ** The study aims at collecting data that could help validate the mathematical model proposed by the authors. Collecting data in itself seems feasible. Designing specific experiments to test the model, such as specifying particular distributions of glycoconjugate residues on cell surfaces, looks more challenging._ _**Overall evaluation:** The project is interesting, but I found the preliminary results a bit weak to justify that the mathematical model worked out by the authors is likely to work._ **Response:** Our project consists of 3 parts ? a theoretical one (a set of ideas converted into mathematical formalization), modeling one and an experimental one (for which we are trying to find support). The modeling part, which we have included in the proposal, is based on the very simplified version of the theoretical part. We use it for better exploring our theoretical conjectures and as a possible proof-of-concept. We are planning to move towards a more complex and sophisticated model driven by the development of the theoretical part together with necessary experimental data.

Idea 5: Molecular code for geometry of morphogenesispage is loading…