Ciotlos, Mao, and colleagues describe the genome sequencing of BT-474, a human cell line model for hormone-dependent breast cancer. The authors tabulate a list of coding variants in some genes previously associated with cancer and assert (but don't actually show) that several anecdotal examples of known translocations are supported by these data. Major points These data may provide a useful resource for groups working with BT-474, but this manuscript barely describes the dataset beyond its most superficial aspects (e.g., file/diretctory structures). If there is some utility in generating cell line reference maps (and indeed there may be), an argument or a case study should be provided to illustrate how these data can be useful, for instance to relate the cell line's genotypes to known molecular or cellular phenotypes (e.g., drug sensitivity, hormone responsiveness, mutator status). Even a purely descriptive manuscript could provide a much richer analysis of the data -- for instance, instead of attributing the excess of homozygous variants as "almost certainly the result of loss of heterozygosity … across all chromosomes", the extent and locations of LOH should be cataloged and summarized. As the authors note, very few cell lines have been subjected to whole genome sequencing analysis. Among these, only a few have been sequenced in a haplotype-resolved manner as done here, and this work would be greatly strengthened by a description of that process and how the resulting phase information can be used (e.g., for structural variant discovery). Essentially no methodological detail is provided for bioinformatics analyses. Minor points The authors should include a detailed comparison to other published work characterizing this cell line through cytogenetic analysis (reference 2, Rondon-Logos et al) or targeted sequencing (Barretina et al, Nature, 2012). Translocations appear to be called much more frequently among the two LFR libraries versus the STD shotgun library. This discrepancy is not mentioned. Does this excess represent false positives on the part of LFR (e.g., chimeric reads resulting from whole-genome amplification) or lack of sensitivity in the STD libraries, or both? Also, the statement that many of the chromosomal translocation calls "are also in agreement with spectral karyotype (SKY) results" doesn't seem to be supported by any analysis in the manuscript. This assertion should be removed or supported. The authors state that the lower ratio of homozygous to heterozygous SNVs likely represents the effects of LOH. This should be explored, for instance by estimating the fraction of the genome impacted by LOH and simulating the effect upon this ratio using WGS variant callsets from healthy, anscestry-matched invididuals (e.g., CEU from 1000 Genoems) Codon numbering appears to be off by one for many of the variants listed in Table 2 (column "Protein Position").

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Ciotlos and colleagues' Data Note on sequencing of the BT-474 cell line is improved in its revised form and may provide a useful reference for groups using these cells. The added comparisons to other analyses of the same cell line provide essential benchmarks of the quality and limitations of these data, and the moderated tone of this revised text is more appropriate than the original. Minor points: (1) The added comparison of Complete Genomics translocation calls to those from two earlier RNA-seq studies is helpful, though it's unfortunate that the CG analysis was limited to interchromosomal translocations when it is apparent from previous reports that intrachromoosmal events are also frequent. Although translocation calling is challenging it is perhaps troubling that 2 of 5 validated events are missed (60% sensitivity) and the authors may wish to comment on whether these two are apparent in their raw alignments (for instance in individual LFR wells) and whether improved algorithms might pick them up. (2) "Circulos" should be "Circos"

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below. If your reply is yes to any, please give details below.

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I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.

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Authors' response to reviews: (http://www.gigasciencejournal.com/imedia/1128448963200686_comment.pdf)

The reviewed version of the manuscript can be seen here:

All revised versions are also available: