Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Analyzing the association of SCNA boundaries with replication timing

Nature Biotechnology volume 30, pages 1045–1046 (2012)Cite this article

Subjects

De and Michor respond

Our paper1 analyzed DNA replication timing patterns at the two boundaries of somatic copy-number alterations (SCNAs) in a large number of cancer samples and reported that, in general, these boundaries tend to be replicated at the same time during cell division. We found that the observed frequency of such events is significantly higher than the pattern expected by chance, based upon two independent statistical strategies: Fisher's test and a permutation analysis. Bilke and Ginden2 now highlight the fact that although individual replication timing domains are typically short, the human genome contains many higher-order replication timing structures, wherein long stretches of early- or late-replicating domains are interrupted only briefly by short regions with different replication timing. They argue that ignoring such structures would lead to an overestimation of the association between replication timing and SCNA boundaries, and therefore they prefer permutation analyses to Fisher's test. Nevertheless, when Bilke and Ginden2 repeat our analyses, they reproduce the published results and confirm the q value of <1 × 10−5 that we reported1. They caution, however, that the statistical significance of the permutation analysis could be driven by the large size of the data set and might decrease when unknown biases are taken into account (for example, permutation across chromosomes instead of within chromosomes).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The distribution of observed/expected values obtained using a simple permutation approach for SCNAs grouped according to their size, with permutation performed within chromosomes.
Figure 2: Comparison of the enrichment using Fisher's test and permutation test for SCNAs of length > 5 Mb.
Figure 3: The distribution of observed/expected values obtained using a simple permutation approach for SCNAs grouped according to their size, with permutation performed across chromosomes.

References

  1. De, S. & Michor, F. Nat. Biotechnol 29, 1103–1108 (2011).

    Article  CAS  Google Scholar 

  2. Bilke, S. & Gindin, Y. Nat. Biotechnol. 30, 1043–1045 (2012).

    Article  CAS  Google Scholar 

  3. Beroukhim, R. et al. Nature 463, 899–905 (2010).

    Article  CAS  Google Scholar 

  4. Hastings, P.J., Lupski, J.R., Rosenberg, S.M. & Ira, G. Nat. Rev. Genet. 10, 551–564 (2009).

    Article  CAS  Google Scholar 

  5. Misteli, T. & Soutoglou, E. Nat. Rev. Mol. Cell Biol. 10, 243–254 (2009).

    Article  CAS  Google Scholar 

  6. Zhang, Y. et al. Cell 148, 908–921 (2012).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    Subhajyoti De & Franziska Michor

  2. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA

    Subhajyoti De & Franziska Michor

Authors
  1. Subhajyoti De
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Franziska Michor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Franziska Michor.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De, S., Michor, F. Analyzing the association of SCNA boundaries with replication timing. Nat Biotechnol 30, 1045–1046 (2012). https://doi.org/10.1038/nbt.2414

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt.2414

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer