PT  - JOURNAL ARTICLE
AU  - Arzalluz-Luque, Angeles
AU  - Salguero, Pedro
AU  - Tarazona, Sonia
AU  - Conesa, Ana
TI  - <em>Acorde</em>: unraveling functionally-interpretable networks of isoform co-usage from single cell data
AID  - 10.1101/2021.05.07.441841
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.07.441841
4099  - http://biorxiv.org/content/early/2021/05/09/2021.05.07.441841.short
4100  - http://biorxiv.org/content/early/2021/05/09/2021.05.07.441841.full
AB  - Alternative splicing (AS) is a highly-regulated post-transcriptional mechanism known to modulate isoform expression within genes and contribute to cell-type identity. However, the extent to which alternative isoforms establish co-expression networks that may relevant in cellular function has not been explored yet. Here, we present acorde, a pipeline that successfully leverages bulk long reads and single-cell data to confidently detect alternative isoform co-expression relationships. To achieve this, we developed and validated percentile correlations, a novel approach that overcomes data sparsity and yields accurate co-expression estimates from single-cell data. Next, acorde uses correlations to cluster co-expressed isoforms into a network, unraveling cell type-specific alternative isoform usage patterns. By selecting same-gene isoforms between these clusters, we subsequently detect and characterize genes with co-differential isoform usage (coDIU) across neural cell types. Finally, we predict functional elements from long read-defined isoforms and provide insight into biological processes, motifs and domains potentially controlled by the coordination of post-transcriptional regulation.Competing Interest StatementThe authors have declared no competing interest.