Prediction of potent shRNAs with a sequential classification algorithm.

Journal: Nature biotechnology
Published Date: Apr 1, 2017

Abstract

We present SplashRNA, a sequential classifier to predict potent microRNA-based short hairpin RNAs (shRNAs). Trained on published and novel data sets, SplashRNA outperforms previous algorithms and reliably predicts the most efficient shRNAs for a given gene. Combined with an optimized miR-E backbone, >90% of high-scoring SplashRNA predictions trigger >85% protein knockdown when expressed from a single genomic integration. SplashRNA can significantly improve the accuracy of loss-of-function genetics studies and facilitates the generation of compact shRNA libraries.

Authors

  • Raphael Pelossof
    Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Lauren Fairchild
    Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Chun-Hao Huang
    Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Christian Widmer
    Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Vipin T Sreedharan
    Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Nishi Sinha
    Mirimus Inc., Woodbury, New York, USA.
  • Dan-Yu Lai
    Mirimus Inc., Woodbury, New York, USA.
  • Yuanzhe Guan
    Mirimus Inc., Woodbury, New York, USA.
  • Prem K Premsrirut
    Mirimus Inc., Woodbury, New York, USA.
  • Darjus F Tschaharganeh
    Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Thomas Hoffmann
    Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
  • Vishal Thapar
    Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Qing Xiang
    RNAi Core, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Ralph J Garippa
    RNAi Core, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Gunnar Rätsch
    Memorial Sloan-Kettering Cancer Center, New York City, New York, United States of America.
  • Johannes Zuber
    Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
  • Scott W Lowe
    Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Christina S Leslie
    Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Christof Fellmann
    Mirimus Inc., Woodbury, New York, USA.

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