Correcting the Mean-Variance Dependency for Differential Variability Testing Using Single-Cell RNA Sequencing Data.

Abstract:

:Cell-to-cell transcriptional variability in otherwise homogeneous cell populations plays an important role in tissue function and development. Single-cell RNA sequencing can characterize this variability in a transcriptome-wide manner. However, technical variation and the confounding between variability and mean expression estimates hinder meaningful comparison of expression variability between cell populations. To address this problem, we introduce an analysis approach that extends the BASiCS statistical framework to derive a residual measure of variability that is not confounded by mean expression. This includes a robust procedure for quantifying technical noise in experiments where technical spike-in molecules are not available. We illustrate how our method provides biological insight into the dynamics of cell-to-cell expression variability, highlighting a synchronization of biosynthetic machinery components in immune cells upon activation. In contrast to the uniform up-regulation of the biosynthetic machinery, CD4+ T cells show heterogeneous up-regulation of immune-related and lineage-defining genes during activation and differentiation.

journal_name

Cell Syst

journal_title

Cell systems

authors

Eling N,Richard AC,Richardson S,Marioni JC,Vallejos CA

doi

10.1016/j.cels.2018.06.011

subject

Has Abstract

pub_date

2018-09-26 00:00:00

pages

284-294.e12

issue

3

eissn

2405-4712

issn

2405-4720

pii

S2405-4712(18)30278-3

journal_volume

7

pub_type

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