Few-shot learning creates predictive models of drug response that translate from high-throughput screens to individual patients.

Journal: Nature cancer
Published Date:

Abstract

Cell-line screens create expansive datasets for learning predictive markers of drug response, but these models do not readily translate to the clinic with its diverse contexts and limited data. In the present study, we apply a recently developed technique, few-shot machine learning, to train a versatile neural network model in cell lines that can be tuned to new contexts using few additional samples. The model quickly adapts when switching among different tissue types and in moving from cell-line models to clinical contexts, including patient-derived tumor cells and patient-derived xenografts. It can also be interpreted to identify the molecular features most important to a drug response, highlighting critical roles for and in the response to CDK inhibition and and in the response to ATM inhibition. The few-shot learning framework provides a bridge from the many samples surveyed in high-throughput screens (-of-many) to the distinctive contexts of individual patients (-of-one).

Authors

  • Jianzhu Ma
    Toyota Technological Institute at Chicago, 6045 S. Kenwood Ave. Chicago, Illinois 60637 USA.
  • Samson H Fong
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Yunan Luo
    School of Computational Science and Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
  • Christopher J Bakkenist
    Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • John Paul Shen
    Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Soufiane Mourragui
    Division of Molecular Carcinogenesis, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Lodewyk F A Wessels
    Division of Molecular Carcinogenesis, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
  • Marc Hafner
    Department of Bioinformatics and Computational Biology, Genentech, Inc., South San Francisco, CA, USA.
  • Roded Sharan
    Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.
  • Jian Peng
    Department of Computer Science, University of Illinois Urbana-Champaign, Urbana, IL, USA.
  • Trey Ideker