Visualizing structure and transitions in high-dimensional biological data

Nat Biotechnol. 2019 Dec;37(12):1482-1492. doi: 10.1038/s41587-019-0336-3. Epub 2019 Dec 3.

Abstract

The high-dimensional data created by high-throughput technologies require visualization tools that reveal data structure and patterns in an intuitive form. We present PHATE, a visualization method that captures both local and global nonlinear structure using an information-geometric distance between data points. We compare PHATE to other tools on a variety of artificial and biological datasets, and find that it consistently preserves a range of patterns in data, including continual progressions, branches and clusters, better than other tools. We define a manifold preservation metric, which we call denoised embedding manifold preservation (DEMaP), and show that PHATE produces lower-dimensional embeddings that are quantitatively better denoised as compared to existing visualization methods. An analysis of a newly generated single-cell RNA sequencing dataset on human germ-layer differentiation demonstrates how PHATE reveals unique biological insight into the main developmental branches, including identification of three previously undescribed subpopulations. We also show that PHATE is applicable to a wide variety of data types, including mass cytometry, single-cell RNA sequencing, Hi-C and gut microbiome data.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Animals
  • Big Data
  • Cell Differentiation
  • Cells, Cultured
  • Computer Simulation
  • Databases, Genetic
  • Gastrointestinal Microbiome
  • Genomics / methods*
  • High-Throughput Screening Assays / methods*
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Mice
  • Sequence Analysis, RNA
  • Single-Cell Analysis