A geometric approach to characterize the functional identity of single cells

Nat Commun. 2018 Apr 17;9(1):1516. doi: 10.1038/s41467-018-03933-2.

Abstract

Single-cell transcriptomic data has the potential to radically redefine our view of cell-type identity. Cells that were previously believed to be homogeneous are now clearly distinguishable in terms of their expression phenotype. Methods for automatically characterizing the functional identity of cells, and their associated properties, can be used to uncover processes involved in lineage differentiation as well as sub-typing cancer cells. They can also be used to suggest personalized therapies based on molecular signatures associated with pathology. We develop a new method, called ACTION, to infer the functional identity of cells from their transcriptional profile, classify them based on their dominant function, and reconstruct regulatory networks that are responsible for mediating their identity. Using ACTION, we identify novel Melanoma subtypes with differential survival rates and therapeutic responses, for which we provide biomarkers along with their underlying regulatory networks.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Cell Differentiation / genetics*
  • Cell Line, Tumor
  • Datasets as Topic
  • Gene Expression Profiling / methods*
  • Gene Regulatory Networks / physiology
  • Humans
  • Melanoma / genetics
  • Melanoma / therapy
  • Mice
  • Models, Genetic*
  • Phenotype
  • Single-Cell Analysis / methods*
  • Survival Rate
  • Transcriptome / physiology*
  • Treatment Outcome
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers, Tumor