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Journal Articles Communications Biology Year : 2020

Controlling technical variation amongst 6693 patient microarrays of the randomized MINDACT trial

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Anke Witteveen
  • Function : Author
Inès Beumer
  • Function : Author
Leonie Delahaye
  • Function : Author
Diederik Wehkamp
  • Function : Author
Jeroen van den Akker
  • Function : Author
Mireille Snel
  • Function : Author
Bob Chan
  • Function : Author
Arno Floore
  • Function : Author
Niels Bakx
  • Function : Author
Guido Brink
  • Function : Author
Coralie Poncet
  • Function : Author
Jan Bogaerts
  • Function : Author
Mauro Delorenzi
  • Function : Author
Martine Piccart
  • Function : Author
Emiel Rutgers
  • Function : Author
Fatima Cardoso
  • Function : Author
Terence Speed
  • Function : Author
Laura van ’t Veer
  • Function : Author
Annuska Glas
  • Function : Author

Abstract

Gene expression data obtained in large studies hold great promises for discovering disease signatures or subtypes through data analysis. It is also prone to technical variation, whose removal is essential to avoid spurious discoveries. Because this variation is not always known and can be confounded with biological signals, its removal is a challenging task. Here we provide a step-wise procedure and comprehensive analysis of the MINDACT microarray dataset. The MINDACT trial enrolled 6693 breast cancer patients and prospectively validated the gene expression signature MammaPrint for outcome prediction. The study also yielded a full-transcriptome microarray for each tumor. We show for the first time in such a large dataset how technical variation can be removed while retaining expected biological signals. Because of its unprecedented size, we hope the resulting adjusted dataset will be an invaluable tool to discover or test gene expression signatures and to advance our understanding of breast cancer.
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Dates and versions

hal-02990043 , version 1 (05-11-2020)

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Laurent Jacob, Anke Witteveen, Inès Beumer, Leonie Delahaye, Diederik Wehkamp, et al.. Controlling technical variation amongst 6693 patient microarrays of the randomized MINDACT trial. Communications Biology, 2020, 3, ⟨10.1038/s42003-020-1111-1⟩. ⟨hal-02990043⟩
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