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Comment re: A Comparison of DNA Copy Number Profiling Platforms

Discovery and Translational Medicine, GlaxoSmithKline, King of Prussia, Pennsylvania

Bin Feng, Elena Ivanova, Ilana Perna and Alexei Protopopov

Center for Applied Cancer Science, the Belfer Institute for Innovative Cancer Science, Boston, Massachusetts

Cristina Nogueira

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts

Lynda Chin

Center for Applied Cancer Science, the Belfer Institute for Innovative Cancer Science, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts and Department of Dermatology, Harvard Medical School, Boston, Massachusetts

Katherine Nathanson

Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania

In Response:The letter from Coe and colleagues acknowledges the values of our systematic approach in comparing DNA copy number profiling platforms but disagrees with how resolution and coverage were defined in the study.

We agree with Coe and colleagues that no individual aspect of platform performance, such as resolution, can be measured as a single metric. The actual minimal alteration size that can be reliably detected by a platform depends upon multiple variables including local probe spacing, sequence complexity, and genome ploidy. In our case, the calculated effective resolution is a point estimate of the size of DNA alteration one could expect to detect under comparable conditions. The value of this calculation thus resides in the relationship between array density when controlling for array platform. In this case, we found a 4.5-fold increase in effective resolution with a similar fold increase in probe density for both the Affymetrix 100K/500K and Agilent 44K/185K platforms. The difference between our empirical estimate of 17.7 kb as the effective resolution of the Affymetrix 500K platform and the theoretical calculation reported by Coe and colleagues (1) may be due to fact that these studies emphasized 2-fold versus 1.5-fold alterations, respectively. We also agree with Coe and colleagues in that statistical or heuristic approaches to defining breakpoints are advantageous. As such, we used a segmentation-based approach (2) for the analyses of focal alterations in this study.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

References

1. Coe BP, Ylstra B, Carvalho B, Meijer GA, Macaulay C, Lam WL. Resolving the resolution of array CGH. Genomics 2007;89:647–53.[CrossRef][Medline]
2. Olshen AB, Venkatraman ES, Lucito R, Wigler M. Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics 2004;5:557–72.[Abstract]

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