Holistic View on the Structure of Immune Response: Petri Net Model

Round 1

Reviewer 1 Report

The authors establish a model of the lymph node based on Petri net formalism with asynchronous firing rule. The model was validated and used in in silico knockout analysis. One of the main problems of the manuscript is that the reasons for the establishment of the proposed model are not appropriately justified. I give more detailed comments below. 

 

1) Please discuss the benefits of your approach in comparison to alternative lymph node modelling approaches. These approaches are mentioned in the paper, however, you should emphasise the rationale behind constructing and applying a Petri net model. More precisely, why should a researcher or a clinician choose your model instead of other state-of-the-art models reported in the literature. Why is your model better than its alternatives? In which scenarios does your model prevail and in which scenarios does your model fail.

 

2) The established model should be compared to other existing models, also on specific analyses, such as in silico knockout analysis as reported in the paper. 

 

3) Please discuss possible (clinical) applications of the proposed model.

 

4) Please discuss the possibilities to personalise the model to a specific individual, to a specific condition and/or to a specific disease.

 

5) Certain biological applications of Petri net modelling are mentioned. However, additional applications of Petri net modelling and their extensions in the context of biomedical research should be discussed. For example, Petri nets have been extended with fuzzy logic approaches in the context of gene regulatory network modelling (https://doi.org/10.3233/FI-2018-1675), they have been combined with ODEs to model signalling networks (https://www.nature.com/articles/s41598-022-04849-0), etc.

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Dear authors

Title: Petri net model of the lymph node

The paper is interesting but few comments are presented to improve the paper as:

1. The title must be improved

2. English needs carefully attention 

3. Abstract should be written in such a way that can present the clear picture of the work.

4. The current abstract can be used as an organization of the paper

5. Introduction needs to improve also and provide clear meanings of the work

6. After the result headings, some detail of the work must be provided

7. Improve the conclusions

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

In this work the authors addressed the immune response of the lymphatic system. They introduced a Petri net model and analyzed it according to its invariant properties, applying, for example, transition invariants, manatee invariants and in silico knockout. The topic is of interest and the paper is well written, but some points need to be improved:

 

The Discussion chapter is largely a repetition of the description of the research carried out. It should be more of a critical assessment of the results obtained in the research carried out by other authors.

 

The paper lacks reference to previous work on using Petri nets for modeling similar systems, and inflammatory systems in specific.

 

It is hard to evaluate the novelty of the findings and conclusions. The conclusions should be better explained and elaborated. The results should be put in context with what has been published previously.

 

As far as the model evaluation is concerned. Additional to the formal evaluation for model consistency (e.g. CTI validation) an evaluation of the model to comply with biological knowledge is also needed. How can we know that the constructed model represents correctly the known biology?

 

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The authors have addressed my concerns in their revision.

Reviewer 2 Report

Accepted in present form