Isoform-level gene expression patterns in single-cell RNA-sequencing data

Trung Nghia Vu, Quin F Wills, Krishna R Kalari, Nifang Niu, Liewei Wang, Yudi Pawitan, Mattias Rantalainen, Janet Kelso
<span title="2018-02-27">2018</span> <i title="Oxford University Press (OUP)"> <a target="_blank" rel="noopener" href="" style="color: black;">Bioinformatics</a> </i> &nbsp;
Motivation: RNA sequencing of single cells enables characterization of transcriptional heterogeneity in seemingly homogeneous cell populations. Single-cell sequencing has been applied in a wide range of researches fields. However, few studies have focus on characterization of isoformlevel expression patterns at the single-cell level. In this study, we propose and apply a novel method, ISOform-Patterns (ISOP), based on mixture modeling, to characterize the expression patterns of isoform pairs
more &raquo; ... m the same gene in single-cell isoform-level expression data. Results: We define six principal patterns of isoform expression relationships and describe a method for differential-pattern analysis. We demonstrate ISOP through analysis of single-cell RNA-sequencing data from a breast cancer cell line, with replication in three independent datasets. We assigned the pattern types to each of 16 562 isoform-pairs from 4929 genes. Among those, 26% of the discovered patterns were significant (P<0.05), while remaining patterns are possibly effects of transcriptional bursting, dropout and stochastic biological heterogeneity. Furthermore, 32% of genes discovered through differentialpattern analysis were not detected by differential-expression analysis. Finally, the effects of drop-out events and expression levels of isoforms on ISOP's performances were investigated through simulated datasets. To conclude, ISOP provides a novel approach for characterization of isoform-level preference, commitment and heterogeneity in single-cell RNA-sequencing data.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.1093/bioinformatics/bty100</a> <a target="_blank" rel="external noopener" href="">pmid:29490015</a> <a target="_blank" rel="external noopener" href="">pmcid:PMC6041805</a> <a target="_blank" rel="external noopener" href="">fatcat:67pqyb35cbbnnjl3hhg6xjyx4u</a> </span>
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