No Cell Left behind: Automated, Stochastic, Physics-Based Tracking of Every Cell in a Dense, Growing Colony

Round 1

Reviewer 1 Report

This work proposes Cell Universe, which is a proof-of-concept algorithm for building a physics-based simulation model (called the "universe") of all the members of a colony of cells. The aim of the approach is to segment the cells and track their motion also in noisy scenarios.

The manuscript is overall interesting, but the novelty needs to be pointed out.
Moreover, careful proofreading would be beneficial.

My main concerns are listed in what follows.

1) Abstract: Some headings are missing and all of them have to be. Please check other articles recently published on Applied Sciences.
Moreover, conclusive remarks and take-home messages are missing.

2) Keywords: more specific keywords should be added.

3) Figure 2: the caption should be extended to better explain the graphical representation.

4) Considering nature-inspired image processing, such as watershed, please discuss this relevant review paper:
Rundo, L., Militello, C., Vitabile, S., Russo, G., Sala, E., & Gilardi, M. C. (2020). A Survey on Nature-Inspired Medical Image Analysis: A Step Further in Biomedical Data Integration. Fundamenta Informaticae, 171(1-4), 345-365. DOI: 10.3233/FI-2020-1887

5) Concerning watershed-based approaches, please consider introducing this work:
Gamarra, M., Zurek, E., Escalante, H. J., Hurtado, L., & San-Juan-Vergara, H. (2019). Split and merge watershed: A two-step method for cell segmentation in fluorescence microscopy images. Biomedical Signal Processing and Control, 53, 101575. DOI: 10.1016/j.bspc.2019.101575

6) The generation of the synthetic samples has to be better explained.

7) Did the Authors perform a systematic study (e.g., sensitivity analysis) at various levels of noise?

8) Section 5: conclusive remarks need to be extended and clarified, as well as a feasible plan for future work should be provided (along with the described technical details).

9) The English language needs to be revised. For instance, the use of abbreviated forms (for instance, "can't") has to be avoided.

Author Response

See attached

Author Response File: Author Response.pdf

Reviewer 2 Report

I really appreciate this work. The paper is well written and clear, results interesting and very relevant to the field.

I am eager to see a publicly available version of the code.

Major:

The authors must add in table 1 the processing time.

Minor:

Could the authors add a second example dataset to the paper, using a movie of adherent mammalian cells?

Author Response

See attached.

Author Response File: Author Response.pdf