Скачать или смотреть Franz Arnold Ake: SCALPEL, a pipeline for quantification of isoform at single-cell resolution

Franz Arnold Ake - PHD Student at IDIBELL

Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that that affects more than 70% of human genes. mRNA isoforms generated though APA have distinct 3ʹ ends, which can affect mRNA regulation as well as the resulting proteins. APA is well known to be regulated during cell differentiation and it is a major source of gene regulation in the brain. Yet, it is not known till which extend APA contributes to the transcriptomic variability across individual cell populations. The rapid development of 3’tag-based single-cell RNA sequencing (scRNAseq) has enabled the study of gene expression and the implementation of methods for describing isoform usage at single cell resolution. Yet, most of these methods have low sensitivity when quantifying isoforms at the single-cell level. Here we present SCALPEL, a Nextflow based tool to quantify and characterize isoform differential usage at the single-cell level. Benchmark analysis shows that SCALPEL outperforms current published tools in the identification of genes expressing multiple isoforms and detecting changes in isoform usage. We used SCALPEL to study the changes in isoform usage during the differentiation of human induced pluripotent stem cells (iPSCs) to neural progenitor cells (NPCs). The results from our analysis show clear changes in 3’end usage between iPSCs and NPCs. We aim to use SCALPEL to investigate the role of APA during neural differentiation and how these changes are altered in neurodegenerative diseases.

Nextflow Summit Boston 2025
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