Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):202-7. doi: 10.1073/pnas.1321405111. Epub 2013 Dec 16.

Automatic Classification of Cellular Expression by Nonlinear Stochastic Embedding (ACCENSE).

Author information

1
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.

Abstract

Mass cytometry enables an unprecedented number of parameters to be measured in individual cells at a high throughput, but the large dimensionality of the resulting data severely limits approaches relying on manual "gating." Clustering cells based on phenotypic similarity comes at a loss of single-cell resolution and often the number of subpopulations is unknown a priori. Here we describe ACCENSE, a tool that combines nonlinear dimensionality reduction with density-based partitioning, and displays multivariate cellular phenotypes on a 2D plot. We apply ACCENSE to 35-parameter mass cytometry data from CD8(+) T cells derived from specific pathogen-free and germ-free mice, and stratify cells into phenotypic subpopulations. Our results show significant heterogeneity within the known CD8(+) T-cell subpopulations, and of particular note is that we find a large novel subpopulation in both specific pathogen-free and germ-free mice that has not been described previously. This subpopulation possesses a phenotypic signature that is distinct from conventional naive and memory subpopulations when analyzed by ACCENSE, but is not distinguishable on a biaxial plot of standard markers. We are able to automatically identify cellular subpopulations based on all proteins analyzed, thus aiding the full utilization of powerful new single-cell technologies such as mass cytometry.

KEYWORDS:

CyTOF; FACS; class discovery; immunophenotyping; machine learning

PMID:
24344260
PMCID:
PMC3890841
DOI:
10.1073/pnas.1321405111
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center