PONE-D-22-12933A novel pathogenesis concept of biliary atresia approached by combined molecular strategiesPLOS ONE Dear Dr. Sangkhathat,

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is a nice study describing novel pathogenetic concept of biliary atresia by combined molecular strategies

The method section is ok

Results are also ok

Discussion is adequate

I have no further suggestions

Reviewer #2: As shown in Table 2, of the 75 enrolled cases, twenty-two cases with genetic variants which were related to cholestatic disorders were identified.

It may be an important finding to identify the variants in the related cholestatic jaundice genes in biliary atresia frequently. On the other hand, it is important to show the diagnosis of biliary atresia is correctly made in the subject cases. The authors should show that the genetic abnormality overlaps in the biliary atresia cases after other cholestatic diseases were correctly differentiated.

Based on this point of view, the authors should present the anatomical pattern of biliary atresia studied in these cases, referring to the following article. (1: Anatomical patterns of biliary atresia including hepatic radicles at the porta hepatis influence short- and long-term prognoses. Pancreat Sci. 2021 Nov;28(11):931-941., 2: The anatomic pattern of biliary atresia identified at the time of Kasai hepatoportoenterostomy and early postoperative clearance of

Jaundice are significant predictors of transplant-free survival. Ann Surg. 2011 Oct; 254(4): 577-585.)

In addition, the authors can demonstrate that you have correctly diagnosed cholestatic diseases when the authors show the signs of Alagille syndrome and the findings of liver biopsy.

In addition, the authors conducted a multivariate analysis, including the day of surgery and variant status. Since it has been shown that the anatomical pattern of biliary atresia also has a significant impact on prognosis, we believe that a multivariate analysis, including these factors, would provide important insights.

Reviewer #3: NONE

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Sujit Mohanty

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A novel pathogenesis concept of biliary atresia approached by combined molecular strategies

PONE-D-22-12933R1

Dear Dr. Sangkhathat,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Gregory Tiao, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Well written paper suggesting novel perspective concept in the pathogenesis of BA by exploring genetic variations and biostatistical appraisal

I have no further suggestions

Reviewer #2: Thank you for responding to my comments.

The author replied properly.

The manuscript is well refined and I do not have further comments.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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