Learning unsupervised feature representations for single cell microscopy images with paired cell inpainting

PLoS Comput Biol. 2019 Sep 3;15(9):e1007348. doi: 10.1371/journal.pcbi.1007348. eCollection 2019 Sep.

Abstract

Cellular microscopy images contain rich insights about biology. To extract this information, researchers use features, or measurements of the patterns of interest in the images. Here, we introduce a convolutional neural network (CNN) to automatically design features for fluorescence microscopy. We use a self-supervised method to learn feature representations of single cells in microscopy images without labelled training data. We train CNNs on a simple task that leverages the inherent structure of microscopy images and controls for variation in cell morphology and imaging: given one cell from an image, the CNN is asked to predict the fluorescence pattern in a second different cell from the same image. We show that our method learns high-quality features that describe protein expression patterns in single cells both yeast and human microscopy datasets. Moreover, we demonstrate that our features are useful for exploratory biological analysis, by capturing high-resolution cellular components in a proteome-wide cluster analysis of human proteins, and by quantifying multi-localized proteins and single-cell variability. We believe paired cell inpainting is a generalizable method to obtain feature representations of single cells in multichannel microscopy images.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Computational Biology
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Microscopy / methods*
  • Neural Networks, Computer
  • Single-Cell Analysis / methods*
  • Unsupervised Machine Learning*
  • Yeasts / cytology

Grants and funding

This work was conducted on a GPU generously provided by Nvidia through their academic seeding grant. This work was funded by the National Science and Engineering Research Council (Pre-Doctoral Award), Canada Research Chairs (Tier II Chair), and the Canadian Foundation for Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.