PONE-D-23-21475Exploring NCATS In-House Biomedical Data for Evidence-based Drug RepurposingPLOS ONE

Dear Dr. Zhu,

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==============================This is timely and important manuscript.  Please address the reviews comments.

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Reviewers' comments:

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Reviewer #1: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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5. Review Comments to the Author

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Reviewer #1: The authors provide methods and supporting data illustrating how large and diverse data sets can be connected and queried with deep learning and related computational tools to generate hypotheses about compound bioactivities that may be useful in novel drug discovery. The manuscript is organized and concise and the use of three examples provides good support for the utility of the approach. The work should be of interest to those considering how to make use of large volumes of publicly available data to understand bioactivity of small molecules. Some editing of grammar and increased clarity of statements would be beneficial. It may also be useful for a moderate amount of additional explanations for much of the jargon used in the paper be provided as this may be unfamiliar to many readers. Finally, it would be useful to include a brief discussion of whether the assays used in the analysis were designed to focus on a single molecular mechanism (and, hence, expect higher chemical similarity among active chemicals) or more phenotypic assays containing multiple potential molecular targets (with more chemical diversity expected).

P 2: “pathophysiology-related”

P 3: “Data from Tox21 for toxicology applications has been systematically preprocessed and quality control conducted (QC) [8-10],”

P4: IDG manages two resources including the Target Central Resource Database (TCRD)

collating manage heterogeneous gene/protein datasets and Pharos providing interfaces to access

data from TCRD.[14]

p 4: Meanwhile, the advanced computational techniques, like machine learning and

deep learning has been actively applied to learn patterns in biomedical data related to drugs and

then link them up to the potential of treating alternative diseases.[24-26]”

p 20: “In this study, we demonstrated the use of NCATS in-house biomedical data for supporting drug repurposing.” This may be an overly strong statement. I don’t think drug repurposing was actually shown; but, rather that the approach generates relevant hypotheses.

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Reviewer #1: No

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Exploring NCATS In-House Biomedical Data for Evidence-based Drug Repurposing

PONE-D-23-21475R1

Dear Dr. Zhu,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Robyn L Tanguay, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for completely addressing the reviewer comments and for the grammatical edits of your manuscript.

Reviewers' comments: