Statistics or biology: the zero-inflation controversy about scRNA-seq data

Researchers view vast zeros in single-cell RNA-seq data differently: some regard zeros as biological signals representing no or low gene expression, while others regard zeros as missing data to be corrected. To help address the controversy, here we discuss the sources of biological and non-biological zeros; introduce five mechanisms of adding non-biological zeros in computational benchmarking; evaluate the impacts of non-biological zeros on data analysis; benchmark three input data types: observed counts, imputed counts, and binarized counts; discuss the open questions regarding non-biological zeros; and advocate the importance of transparent analysis.

• NS
  National Science Foundation

  Awards: 2113754, 1846216, DMS-2113754
• AP
  Alfred P. Sloan Foundation
• WM
  W. M. Keck Foundation
• NI
  National Institutes of Health

  Awards: R01GM120507, R35GM140888
• DF
  Directorate for Biological Sciences

  Award: 1846216
• DF
  Directorate for Mathematical and Physical Sciences

  Award: 2113754
• JA
  Johnson and Johnson

  Award: WiSTEM2D Award
• NI
  National Institute of General Medical Sciences

  Awards: R35GM140888, R01GM120507
• DG
  David Geffen School of Medicine, University of California, Los Angeles