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 Systjournal_title
Cell systemsauthors
Eling N,Richard AC,Richardson S,Marioni JC,Vallejos CAdoi
10.1016/j.cels.2018.06.011subject
Has Abstractpub_date
2018-09-26 00:00:00pages
284-294.e12issue
3eissn
2405-4712issn
2405-4720pii
S2405-4712(18)30278-3journal_volume
7pub_type
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