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PharmacoDB: an integrative database for mining in vitro drug screening studies

Petr Smirnov, Victor Kofia, Alexander Maru, Mark Freeman, Chantal Ho, Nehme El-Hachem, George-Alexandru Adam, Wail Ba-alawi, Zhaleh Safikhani, Benjamin Haibe-Kains
doi: https://doi.org/10.1101/195149
Petr Smirnov
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
2Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
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Victor Kofia
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
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Alexander Maru
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
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Mark Freeman
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
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Chantal Ho
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
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Nehme El-Hachem
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
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George-Alexandru Adam
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
3Department of Computer Science, University of Toronto, Toronto, Ontario, Canada
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Wail Ba-alawi
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
2Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
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Zhaleh Safikhani
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
2Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
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Benjamin Haibe-Kains
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
2Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
3Department of Computer Science, University of Toronto, Toronto, Ontario, Canada
4Ontario Institute of Cancer Research, Toronto, Ontario, Canada
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ABSTRACT

Recent pharmacogenomic studies profiled large panels of cancer cell lines against hundreds of approved drugs and experimental chemical compounds. The overarching goal of these screens is to measure sensitivity of cell lines to chemical perturbation, correlate these measures to genomic features, and thereby develop novel predictors of drug response. However, leveraging this valuable data is challenging due to the lack of standards for annotating cell lines and chemical compounds, and quantifying drug response. Moreover, it has been recently shown that the complexity and complementarity of the experimental protocols used in the field result in high levels of technical and biological variation in the in vitro pharmacological profiles. There is therefore a need for new tools to facilitate rigorous comparison and integrative analysis of large-scale drug screening datasets. To address this issue, we have developed PharmacoDB (pharmacodb.pmgenomics.ca), a database integrating the largest pharmacogenomic studies published to date. Here, we describe how the curation of cell line and chemical compound identifiers maximizes the overlap between datasets and how users can leverage such data to compare and extract robust drug phenotypes. PharmacoDB provides a unique resource to mine a compendium of curated pharmacogenomic datasets that are otherwise disparate and difficult to integrate.

Key points

  • Curation of cell line and drug identifiers in the largest pharmacogenomic studies published to date

  • Uniform processing of drug sensitivity data to reduce heterogeneity across studies

  • Multiple drug response summary metrics enabling visual comparison and integrative analysis

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted September 27, 2017.
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PharmacoDB: an integrative database for mining in vitro drug screening studies
Petr Smirnov, Victor Kofia, Alexander Maru, Mark Freeman, Chantal Ho, Nehme El-Hachem, George-Alexandru Adam, Wail Ba-alawi, Zhaleh Safikhani, Benjamin Haibe-Kains
bioRxiv 195149; doi: https://doi.org/10.1101/195149
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PharmacoDB: an integrative database for mining in vitro drug screening studies
Petr Smirnov, Victor Kofia, Alexander Maru, Mark Freeman, Chantal Ho, Nehme El-Hachem, George-Alexandru Adam, Wail Ba-alawi, Zhaleh Safikhani, Benjamin Haibe-Kains
bioRxiv 195149; doi: https://doi.org/10.1101/195149

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