Exploring single-cell data with deep multitasking neural networks.

Journal: Nature methods
PMID:

Abstract

It is currently challenging to analyze single-cell data consisting of many cells and samples, and to address variations arising from batch effects and different sample preparations. For this purpose, we present SAUCIE, a deep neural network that combines parallelization and scalability offered by neural networks, with the deep representation of data that can be learned by them to perform many single-cell data analysis tasks. Our regularizations (penalties) render features learned in hidden layers of the neural network interpretable. On large, multi-patient datasets, SAUCIE's various hidden layers contain denoised and batch-corrected data, a low-dimensional visualization and unsupervised clustering, as well as other information that can be used to explore the data. We analyze a 180-sample dataset consisting of 11 million T cells from dengue patients in India, measured with mass cytometry. SAUCIE can batch correct and identify cluster-based signatures of acute dengue infection and create a patient manifold, stratifying immune response to dengue.

Authors

  • Matthew Amodio
    Department of Computer Science, Yale University, New Haven, CT, USA.
  • David van Dijk
    Department of Internal Medicine, Yale University, New Haven, CT, USA; Department of Computer Science, Yale University, New Haven, CT, USA.
  • Krishnan Srinivasan
    Department of Computer Science, Yale University, New Haven, CT, USA.
  • William S Chen
    School of Medicine, Yale University, New Haven, CT, USA.
  • Hussein Mohsen
    Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.
  • Kevin R Moon
    Department of Mathematics and Statistics, Utah State University, Logan, UT, USA.
  • Allison Campbell
    School of Medicine, Yale University, New Haven, CT, USA.
  • Yujiao Zhao
    Department of Rheumatology, Yale University, New Haven, CT, USA.
  • Xiaomei Wang
    The Department of Mechanical Engineering, The University of Hong Kong, Pokfulam, Hong Kong.
  • Manjunatha Venkataswamy
    Department of Neurovirology, NIMHANS, Bangalore, India.
  • Anita Desai
    Department of Neurovirology, NIMHANS, Bangalore, India.
  • V Ravi
    Department of Neurovirology, NIMHANS, Bangalore, India.
  • Priti Kumar
    Department of Microbial Pathogenesis, Yale University, New Haven, CT, USA.
  • Ruth Montgomery
    Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
  • Guy Wolf
    Department of Mathematics and Statistics, Université de Montréal, Montréal, Quebec, Canada.
  • Smita Krishnaswamy
    Department of Computer Science, Yale University, New Haven, CT, USA. smita.krishnaswamy@yale.edu.