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Response to Reviewers#

When revising a manuscript based on peer review, a well-structured response document is essential. It shows that you've addressed the feedback thoughtfully and improved the manuscript accordingly.

Tips for Writing#

  • Be clear, respectful, and constructive.
  • Acknowledge valid criticisms, and explain your rationale when you disagree.
  • Reference exact changes made in the revised manuscript.

Format#

  • Reviewer comments: Use black text to quote reviewer feedback.
  • Your responses: Use blue text to clearly separate your reply.
  • Number or bullet each comment for clarity.
  • Refer to line numbers, sections, or figures in your revised manuscript wherever relevant.

Example Structure#

Reviwer comments are in plain text, responses are bold and italicized

Short Example

Reviewer 1
The introduction is vague about the specific hypothesis being tested.

Thank you for the feedback. We revised the second paragraph of the Introduction to clearly state the hypothesis: "We hypothesized that [...]." (Lines 45–50)

Long Example

Reviewer 2

This is a well written manuscript presenting artificial intelligence approaches to define bimodal gene expression as a tool to determine drug sensitivity in cancer.

The premise of the work is that bimodal gene assessment would be a superior predictor of drug sensitivity. This work could deeply influence drug development and enhance the preclinical target validation in a comprehensive and robust way.

The authors present extensive data demonstrating the role of AI in assessing bimodal gene expression as a comprehensive biomarker strategy.

There are many interesting findings in this manuscript, but there are several areas of uncertainty and statements that should be addressed to place these findings in context of current and past clinical drug development and its relevance.

We thank the reviewer for her/his positive assessment of our manuscript. We have added our response to each comment below.

Introduction:

1) The introduction is somewhat unclear, are the authors focusing on gene expression as predictive markers of drug sensitivity assessment tools or prognostic markers as some of the examples that listed may suggest?

The focus of the manuscript is on genes with bimodal expression as candidate predictive biomarkers of drug sensitivity. The examples showcase the usefulness of bimodal genes in various biomarker settings as a motivation for their relevance. We have enhanced the relevant Introduction section to remove any confusion.

Revised manuscript - Section:

For example, estrogen receptor (ESR1) bimodal expression defines two biological states within breast cancer patients. These states have been used to stratify breast cancer patients into the clinically-relevant subtypes (ER+/-) and derive treatment decisions. Another example in cancer genomics is the use of 73 bimodal genes within ovarian cancer to define molecular subtypes with distinct survival rate 12. We also have shown that epithelial-to-mesenchymal transition (EMT) related genes were found to be bimodal pan-cancer and predictive of response to statin class of drugs 13.

📌 Use both the cover letter and the response to reviewers to frame your manuscript in the best light and demonstrate professionalism throughout the review process.