The authors have responded to all of the questions and provided additional information and clarifications where necessary. The authors also performed new experiments to expand and strengthen the indicated sections, resolved any technical issues and modified the text according to the suggestions.

I do not have anything further to add apart from reporting some minor text errors I identified with a second read-through.

The following is a list of points I identified in the text that require editing: 1. Intro, page 2 at the end of the section where the authors list their goals "(v) allowing for efficient parallelizations over different platforms;" - I believe that sentence should followed by a '.'. 2. Similar to 1 in Materials and methods, first paragraph after "(v) cluster collection, visualization and annotation;" ; should be replaced with . 3. These repeats 4 times in the newly added text that follows a. After "specific tools; Firstly, from..." b. After "smaller than the entire input data; In the second step after..." c. After "maximization algorithm [28]; Thirdly after..". Perhaps a comma is also needed after "Thirdly"? d. After "missed in the initial clustering; Finally, ..." 4. In the workflow output paragraph: I believe ending the sentence after "soft partitions" and starting with a new sentence as "soft partitions. In the latter case, elements can belong..." makes the text easier to read. 5. A full stop is needed after subtitle " Orthology sequence extraction from long RNA locus" 6. Page 5, end of column 1 - "To draw a conclusion, however, an extensive SHAPE data would be needed...". Would "To draw a conclusion, however, an extensive SHAPE dataset would be needed.." or "To draw a conclusion, however, extensive SHAPE data would be needed..." be more appropriate here? 7. There is a full stop at the end of title "GraphClust is Scalable." Delete if not purposefully used there 8. Page 6, column 2, right before the FTL paragraph. "And compensatory mutated paired regions; Below we describe..." Replace ; with . 9. Page 7 - The first sentence of the newly added text requires a full stop.

I would encourage the authors to do another read-through of the manuscript in case I missed something.

I am also attaching a doc file, with my full responses (blue colour) to the author comments.

Declaration of competing interests Please complete a declaration of competing interests, considering the following questions: Have you in the past five years received reimbursements, fees, funding, or salary from an organisation that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? Do you hold any stocks or shares in an organisation that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? Do you hold or are you currently applying for any patents relating to the content of the manuscript? Have you received reimbursements, fees, funding, or salary from an organization that holds or has applied for patents relating to the content of the manuscript? Do you have any other financial competing interests? Do you have any non-financial competing interests in relation to this paper? If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If your reply is yes to any, please give details below.

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Authors' response to reviews:

We would like to thank the reviewers for their feedback and the constructive reviewing process.