• Andrea Omicini
    Andrea Omicini, 18/06/2012 20:09

    Dear Prof. Omicini: 

    Re: tracking number JOS-12-0002: article title "A Biochemically-inspired Coordination-based Model for Simulating Intracellular Signalling Pathways" 

    I can now come back to you with a decision about the article you submitted to Journal of Simulation. 

    We think this a very promising article, and would like to invite you to revise and resubmit the article, taking into account the reviewers' comments below. Your paper will be sent for re-review with the same reviewers, and we will then make a final decision. 

    The reviewers' comments were: 

    Referee #1 (Comments for the Author): 

    The authors present a self-organizing system based on biochemical tuple spaces (BTS-SOC) and apply this approach for the simulation of complex interaction patterns of intracellular signaling pathways.
    There are a large number of intracellular signalling pathways responsible for transmitting information within the cell. They fall into two main categories. The majority respond to external stimuli arriving at the cell surface, usually in the form of a chemical signal (neurotransmitter, hormone or growth factor), which is received by receptors at the cell periphery that function as molecular antennae embedded in the plasma membrane. The other categories are the pathways that are activated by signals generated from within the cell. There are a number of metabolic messengers that act from within the cell to initiate a variety of signalling pathways.
    This paper is very interesting because it is not limited only to propose a model for simulating intracellular signaling pathways but is applied to a case study. This allows us to appreciate the important nuances of the approach taken to model different interaction situations as situatedness, adaptivity, locality and topology.
    The paper is well-written and describes in great detail the model in the formalism BTS-SOC. 

    Referee #2 (Comments for the Author): 

    The authors describe the usage of a tuple-based interaction framework for simulating biochemical intracellular signalling pathways. The BTS-SOC seems to be perfectly adapted to the application, so this could have been a really interesting contribution. Unfortunately, the paper is not written in a good way, major rewriting is necessary as especially the organization of the paper should be improved. 

    An initial criticism concerns the relevance of the agent metaphor for the given system. Why there is an agent metaphor necessary? what is the advantage of using agents here? The BTS-SOC framework is based on /implemented with TuCSon which is general beyond agent systems. Also, the treatment of agent-based simulation tools as related works is quite shallow and does not really fit to the rest of the paper. This also shows that there is no inherent reason for calling the work "agent-based". The authors state that sophisticated design of behavioural rules in the environment is missing in "traditional ABM" - whatever they mean with "traditional". But in that generality, this is definitely wrong. To me it does not become clear what sophisticated behavioural rules should be necessary for the given application domain? 

    Maybe it would be easier to argue about this if the overall structure and presentation would be better. After an introduction that relates BTS-SOC to TuCSon and tuple centres, the authors describe on a too abstract way properties of BTS-SOC and how concepts in BTS-SOC correspond to the basic infrastructure. The problem is that the authors do not give information about the basic infrastructure. Without knowing about their coordination concepts, this part is not understandable. For example, what does "publish" mean in this context? So here the paper is clearly not self-contained - which might be acceptable for a conference contribution, but not for a general journal on modeling and simulation. I do not believe that the standard reader of this journal is familiar with Linda-based coordination frameworks as they are suggested for agent-oriented software development. So at least a short characterization of ReSpecT would be necessary. And, in section II, much more (also more formal
    details on the overall system must be given. It remains unclear which parts of the overall infrastructure are new, which ones are just re-naming and which elements are taken from the original interaction frameworks. It also remains unclear how, how much and when reactants are transfered from one compartment to their neighbourhood compartments. What exactly is the role of the rates? How are the temporal dynamics simulated precisely? Initially, the authors mention distributedness of such a system? where do I see this ? 

    Without such a clear introduction to BTS-SOC, the case study also does not become clear. What is part of the case study? What elements are part of the general framework? For example the idea of having the concentration as tuple value is probably belonging to BTS-SOC in general and should be clearly introduced before the case study. How does the Gillespie Algorithm work (case study or framework?)? One or two sentences would be sufficient to characterize. Section III starts with general information on protein pathways that I simply did not understand and for which I'm not sure whether this description is giving information that I need in the case study later on.
    The description of the case study is mixed with information about user interaction and unreadable screenshots. This must be separated: First the specialized framework with everything that is provided by the framework (including a description of its basics), the model of the signalling pathway case study with results also showing the validity of the simulated concentrations in the different compartments including its temporal dynamics. This is completely missing, but is essential for a case study. It would be so easy to display how concentrations change over time in each department, instead of that the authors give text in screenshots? What calibration is necessary in the case study? Is this supported by the framework? Validation? If there is space left then, the authors may indicate that they created a new user interface and describe the features. Mixing the screenshots with a vague description of what user interactions are possible does not show anything about the appropriat
    of the paradigm for the modelling problem. It does not become clear whether the authors had to implement the user interface for the case study or whether it is given by the overall BTS-SOC framework. If it is specific for the case study, how does the BTS-SOC framework support the development of specific user interfaces? 

    all error graphics unreadable!
    Table 4 could be given in a much more readable form. 


    Please make the necessary changes etc. as directed and resubmit BY 1st SEPTEMBER 2012 via the online submission system using the link below. Please add a detailed description of how you have addressed the referees' comments. This will be vital in assessing the next stage decision on your article. 


    If only minor changes are needed the revised article will be checked by the Editorial office and a decision made on whether to accept it for publication. Should significant changes be requested the manuscript may go back out for further review. 

    Thank you once again for your contribution to Journal of Simulation. 

    With kind regards,
    Sarah Parry
    Editorial Assistant
    Journal of the Operational Research Society

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