PONE-D-21-03311

Placental DNA methylation changes and the early prediction of autism in full-term newborns

PLOS ONE

Dear Dr. Radhakrishna,

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Abhishek Kumar, Ph.D.

Academic Editor

PLOS ONE

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Additional Editor Comments (if provided):

Firstly, I am sorry that for delays but it was required for reviewing process.

Please provide answers to question raised by the reviewer. I want to add a few points for the improvement of this manuscript.

a) Please provide a pipeline figure for methods followed in this study.

b) Provide details of the pathway data in the result section and roles of these four pathways in autism.

Looking forward for these changes.

Sincerely

Dr. Abhishek Kumar

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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

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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: Current Manuscript describes the use of placental DNA methylation alterations and the early prediction of autism in full-term newborns. Autism spectrum disorder (ASD) have been previously linked with abnormal brain development and epigenetic dysfunctions during early development stages. The authors hypothesized if placental DNA methylation changes could be used as a prediction tools to elucidate the early pathogenesis of ASD. They performed genome-wide methylation analysis of 14 patients and 10 controls using placental tissue followed Ingenuity Pathway Analysis, six Artificial Intelligence (AI) algorithms including Deep Learning (DL) to investigate the predictive accuracy of CpG markers for autism detection. They identified important biological pathways and genes involved early fetal neurodevelopmental process that influence later cognition and social behavior. Overall, this is an excellent study that provides important insights about the biological pathways involved in ASD. The authors should address the following minor concerns in order to improve the quality of their manuscript.

1. The authors performed genome-wide methylation analysis using 14 patients and 10 controls. The gender of these individuals is not clear. The authors should clearly specify this in the table and methods section.

2. There are few incomplete statements in the manuscript. Line 239, they stated “Further functional studies are required to explore its role in ASD”. What do you mean by further functional analysis here? Little more clarity would be helpful.

3. The authors should consider including few statements in the discussion section if the biological pathways identified in this study are druggable.

4. There are multiple typos, grammatical and syntax errors that the authors should correct.

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Reviewer #1: No

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Placental DNA methylation changes and the early prediction of autism in full-term newborns

PONE-D-21-03311R1

Dear Dr. Radhakrishna,

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,

Abhishek Kumar, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

We are glad to inform that this manuscript is accepted for publication.

Reviewers' comments: