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Drug response consistency in CCLE and CGP

Nature volume 540, pages E9–E10 (2016)Cite this article

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arising from B. Haibe-Kains et al. Nature 504, 389–393 (2013); 10.1038/nature12831

The Cancer Cell Line Encyclopedia1 (CCLE) and Cancer Genome Project2 (CGP) are two independent large-scale efforts to characterize genomes, mRNA expression, and anti-cancer drug dose–responses across cell lines, providing a public resource relating cellular biochemical context to drug sensitivity. A recent study3 analysed correlations between reported dose–response metrics and found inconsistency between CCLE and CGP, thus questioning the validity of not only these, but also other current and future costly large-scale studies. Here, we examine two metrics of drug responsiveness (slope and area under the curve) that we derive from the original CCLE and CGP data, and find reasonable and statistically significant consistency. Our results revive confidence that the CCLE and CGP drug dose–response data are of sufficient quality for meaningful analyses. There is a Reply to this Comment by Safikhani, Z. et al. Nature 540, http://dx.doi.org/10.1038/nature20581 (2016).

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Figure 1: Consistency between pharmacological data in CCLE and CGP.

Change history

  • 19 July 2017

    The link to the Reply (nature20581) was corrected.

References

  1. Barretina, J. et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603–607 (2012)

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  2. Garnett, M. J. et al. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 483, 570–575 (2012)

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  3. Haibe-Kains, B. et al. Inconsistency in large pharmacogenomic studies. Nature 504, 389–393 (2013)

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Authors and Affiliations

  1. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA

    Mehdi Bouhaddou, Matthew S. DiStefano, Eric A. Riesel, Emilce Carrasco, Hadassa Y. Holzapfel, DeAnalisa C. Jones, Gregory R. Smith, Alan D. Stern, Sulaiman S. Somani, T. Victoria Thompson & Marc R. Birtwistle

  2. DToXS LINCS Center, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA

    Marc R. Birtwistle

  3. Systems Biology Center New York, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA

    Marc R. Birtwistle

Authors
  1. Mehdi Bouhaddou
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  2. Matthew S. DiStefano
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  3. Eric A. Riesel
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  4. Emilce Carrasco
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  5. Hadassa Y. Holzapfel
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  6. DeAnalisa C. Jones
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  7. Gregory R. Smith
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  8. Alan D. Stern
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  9. Sulaiman S. Somani
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  10. T. Victoria Thompson
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  11. Marc R. Birtwistle
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Corresponding author

Correspondence to Marc R. Birtwistle.

Extended data figures and tables

Extended Data Figure 1 Examples of typical sensitive versus insensitive dose–response curves.

This document was given to manual curators as example dose–response curves. These idealized data represent various dose–response curves one might encounter in CCLE and/or CGP and indicate how they should be classified.

Extended Data Figure 2 Examples of what the manual curators received.

This is one page, as an example, from the data given to manual curators, which they were instructed to rate as either sensitive or insensitive.

Supplementary information

Supplementary Information

This file contains Supplementary Methods and Supplementary Data. Each data page depicts a different cancer cell line, the name of which is given at the top of each page. On each page, all of the drugs that were tested by both CCLE and CGP are displayed. Drug dose is on the x-axis and percent cell viability is on the y-axis. Blue corresponds to CCLE and red to CGP. Stars indicate the shared dose range between the two studies. The red and blue numbers in the bottom left corner of each subplot are the means across all manual curator ratings for CGP and CCLE, respectively. 1= unanimous sensitivity; 2=unanimous insensitivity. (PDF 13108 kb)

Supplementary Data 1

Discrepantly classified dose response curves. Dose response curves from drug/ cell line pairs that were discrepant in terms of sensitivity classification. Only data in shared dose range is shown. Red dots are CGP, blue are CCLE. (PDF 1474 kb)

Supplementary Data 2

This zipped file contains Supplementary Data - see -read me’ file for details. (ZIP 464 kb)

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Bouhaddou, M., DiStefano, M., Riesel, E. et al. Drug response consistency in CCLE and CGP. Nature 540, E9–E10 (2016). https://doi.org/10.1038/nature20580

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