Discriminative feature of cells characterizes cell populations of interest by a small subset of genes

PLoS Comput Biol. 2021 Nov 19;17(11):e1009579. doi: 10.1371/journal.pcbi.1009579. eCollection 2021 Nov.

Abstract

Organisms are composed of various cell types with specific states. To obtain a comprehensive understanding of the functions of organs and tissues, cell types have been classified and defined by identifying specific marker genes. Statistical tests are critical for identifying marker genes, which often involve evaluating differences in the mean expression levels of genes. Differentially expressed gene (DEG)-based analysis has been the most frequently used method of this kind. However, in association with increases in sample size such as in single-cell analysis, DEG-based analysis has faced difficulties associated with the inflation of P-values. Here, we propose the concept of discriminative feature of cells (DFC), an alternative to using DEG-based approaches. We implemented DFC using logistic regression with an adaptive LASSO penalty to perform binary classification for discriminating a population of interest and variable selection to obtain a small subset of defining genes. We demonstrated that DFC prioritized gene pairs with non-independent expression using artificial data and that DFC enabled characterization of the muscle satellite/progenitor cell population. The results revealed that DFC well captured cell-type-specific markers, specific gene expression patterns, and subcategories of this cell population. DFC may complement DEG-based methods for interpreting large data sets. DEG-based analysis uses lists of genes with differences in expression between groups, while DFC, which can be termed a discriminative approach, has potential applications in the task of cell characterization. Upon recent advances in the high-throughput analysis of single cells, methods of cell characterization such as scRNA-seq can be effectively subjected to the discriminative methods.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cluster Analysis
  • Computer Simulation
  • Gene Expression*
  • Genetic Markers
  • Humans
  • Logistic Models

Substances

  • Genetic Markers

Grants and funding

This work was supported by Core research for evolutional science and technology (JPMJCR16G1 to Y.O. https://www.jst.go.jp/kisoken/crest/en/index.html), Precursory Research for Embryonic Science and Technology (JPMJPR2026 to K.M. https://www.jst.go.jp/kisoken/presto/en/index.html) and Japan society for the promotion of science (JP18H04802, JP18H05527, JP19H05244, JP20H00456, JP20H04846, JP20K21398, and JP21H00232 to Y.O.; JP19H04970, JP19H03158, JP20H05393 and JP21H05755 to K.M. https://www.jsps.go.jp/english/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.