Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

According to the Data guidelines:

1. Scientific Value
   This paper offers value by curating a peer-reviewed dataset that benchmarks data quality in research pipelines. It supports reproducibility in data analysis workflows, aiding validation studies in computational biology. Even if the dataset is rather small, it can contribute to the bigger datasets (I believe?) or will be expanded in the future (will it?)
2. Consistency with Knowledge
   The work is consistent with established knowledge in data management and peer review standards, drawing on FAIR principles and current practices in dataset repositories like Zenodo or Figshare. Small dataset remains the issue. 
3. Weakpoint 1: Limited Multi-Omics Integration
   The dataset underrepresents multi-omics layers (e.g., genomics, proteomics), limiting relevance to personalized medicine, which is important now. Authors can improve theoretically by adding metadata annotations linking to public multi-omics resources (e.g., TCGA) and including correlation matrices in supplementary files, without new experiments, or more data about the families described, including clinical information. 
4. Weakpoint 2: Static Data Presentation
   Data lacks dynamic visualization or interactive formats, reducing utility for modern analyses. Improve by appending Jupyter notebooks with exploratory plots (e.g., dimensionality reduction) generated from the dataset, emphasizing theoretical scalability to longitudinal multi-omics studies.

After all, I'm not fully convinced why these families are so important? Why they differ and should be explored more? 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This study performed whole-genome sequencing on two unrelated high-risk breast cancer families and made the sequencing dataset publicly available. This dataset provides a importance resource for genetic studies of breast cancer and holds certain scientific value and application potential for further exploration of unexplained breast cancer cases.

1. Although multiple candidate genes and variants were identified, no functional validation was conducted. It is recommended that future studies validate the effects of these variants on breast cancer development through cell-based experiments or animal models to further confirm their pathogenicity.
2. The current sample size is relatively small, which may limit the generalizability and statistical power of the findings. It is recommended to expand the sample size by including more breast cancer families without known susceptibility gene mutations to improve the reliability and representativeness of the study.
3. Although the study mentions the potential impact of variants in non-coding regions on breast cancer risk, no in-depth analysis was performed. Future studies should strengthen the detection and analysis of non-coding variants to explore their regulatory mechanisms and biological functions.
4. Although the manuscript states that ethical approval and informed consent were obtained, it does not provide the name of the ethics committee or the approval number. It is recommended to include these details to comply with international publication standards.

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

1. The methods are not described in sufficient detail. The manuscript does not adequately explain the specific workflow used for variant calling, filtering, and annotation. The authors should provide the SNV/indel caller, filtering criteria, and sequencing quality control metrics for each sample.
2. The variant prioritization strategy requires further explanation.
3. The biological significance of some variants should be interpreted more cautiously. Variants annotated in ClinVar as pathogenic/likely pathogenic do not necessarily imply a direct association with breast cancer susceptibility, and overinterpretation should be avoided.
4. The sample size is very small, and the conclusions should therefore be more restrained.
5. The background of prior genetic testing is not sufficiently clear. The manuscript emphasizes that the participants had previously undergone multigene panel testing with negative results, but it does not specify which genes were included in the panel or what criteria were used for variant interpretation.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf