Predicting the Evolution of Syntenies—An Algorithmic Review

Round 1

Reviewer 1 Report

The author presents a comprehensive review of approaches to reconstruct the evolution of genomes from the algorithmic perspective. As such, she mainly focuses on the combinatorial different formulations of the different problems proposed in the literature, while statistics-based ones are not generally mentioned (unless relevant for some specific problems). I find this choice perfectly fine given the target of the journal. 

I enjoyed reading the review, although I am familiar with only a part of the approaches described therein. I have no major concern, but I would suggest providing an introductory explanation of the concepts used in the paper for the CS readers that are not familiar with them. For example, the concept of Horizontal Gene Transfer (mentioned at page 1) cannot be considered already known by the general reader. For this reason, I would suggest to add some figures explaining the basic concepts and the basic definitions (for example, in Section 2). 

Furthermore, I would suggest adding a paragraph explaining the general structure of the review. 

Minor remarks: 

• Line 258, please add the relevant citation (Bulteau, L., Fertin, G., Rusu, I.: Sorting by transpositions is difficult. SIAM Journal on Discrete Mathematics 26(3), 1148–1180 (2012)) 
• Line 325, reconstruction -> reconstructed 
• Details of some references need to be double checked (for example ref 45, 51, 58, 110, 119, 126) 

Author Response

Thank you for your relevant comments that allowed me to improve the manuscript. In fact, there are a lot of biological concepts with which computer science readers may not be familiar. Therefore I have added more explanations, and one figure introducing the different evolutionary events, including horizontal gene transfers. I have also added a figure in Section 2, as suggested, on the different definitions of syntenies, and I have also added a figure in Section 5.1. better explaining the concept of reconciliation. I hope this will help the reader.

I have also added a paragraph explaining the structure of the review at the end of the introduction, added the reference for the NP-hardness result on sorting by transpositions, and corrected the references.

Reviewer 2 Report

The review submitted by N. El-Mabrouk describes a series of computational methods for characterizing homologous genomic regions.

Although I would have preferred a deeper discussion of some fundamental topics, for example, the definition of homology and its limitations, I think that the review is clear and agreeable and that it can be interesting for numerous readers in bioinformatics and evolution biology.

Author Response

Thank you for your kind comments.

I have added some clarification on orthology, paralogy, xenelogy, with the concepts illustrated on a figure. I have actually added three figured to clarify a number of concepts, including horizontal gene transfer.