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Updated: Jan 9, 2026

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations

Published on: October 25, 2018

Determining gene specificity from multivariate single-cell RNA sequencing data.

Nikhila P Swarna¹, A Sina Booeshaghi², Elisabeth Rebboah^3,4

¹Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.

Biorxiv : the Preprint Server for Biology

|December 3, 2025

Summary

This summary is machine-generated.

We developed ember, a novel method for identifying gene specificity in single-cell genomics. Ember reveals complex gene expression patterns across mouse tissues and human cells, highlighting context-dependent gene function.

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Published on: March 23, 2022

Area of Science:

Genomics
Computational Biology
Bioinformatics

Background:

Identifying genes specific to biological categories or experimental conditions is crucial in single-cell genomics.
Existing methods for gene specificity analysis lack a standardized axiomatic approach.

Purpose of the Study:

To develop a robust and axiomatic method for measuring gene specificity.
To apply this method to uncover novel gene expression patterns in mouse and human datasets.

Main Methods:

Developed ember (Entropy Metrics for Biological ExploRation), an axiomatic approach for gene specificity measurement.
Applied ember to single-cell RNA sequencing data from eight mouse tissues and founder strains.
Utilized unsupervised learning on entropy metrics to identify specialized genes.
Extended ember analysis to a human peripheral blood mononuclear cell (PBMC) dataset.

Main Results:

Ember is the only method satisfying four key properties for gene specificity.
Mouse gene specificity is often unintuitive, with context-dependent housekeeping genes and strain-driven cell type switching.
Uncovered shared genes specific to male gonads and kidneys, and stage-specific kidney genes.
Human PBMC variation is concentrated in classical monocytes, with sex, age, and ancestry-specific genes identified.

Conclusions:

Ember provides a powerful, axiomatic tool for gene specificity analysis in single-cell genomics.
The study reveals complex and context-dependent gene expression patterns in mice and humans.
Findings offer insights into genetic variation and provide a roadmap for future research using the murine model.