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Acorde: unraveling functionally-interpretable networks of isoform co-usage from single cell data

View ORCID ProfileAngeles Arzalluz-Luque, Pedro Salguero, View ORCID ProfileSonia Tarazona, View ORCID ProfileAna Conesa
doi: https://doi.org/10.1101/2021.05.07.441841
Angeles Arzalluz-Luque
1Department of Applied Statistics, Operations Research and Quality, Universitat Politècnica de València, Valencia, Spain
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Pedro Salguero
1Department of Applied Statistics, Operations Research and Quality, Universitat Politècnica de València, Valencia, Spain
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Sonia Tarazona
1Department of Applied Statistics, Operations Research and Quality, Universitat Politècnica de València, Valencia, Spain
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  • For correspondence: sotacam@eio.upv aconesa@ufl.edu
Ana Conesa
2Microbiology and Cell Sciences Department, Institute for Food and Agricultural Research, University of Florida, Gainesville, Florida, United States
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  • For correspondence: sotacam@eio.upv aconesa@ufl.edu
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Abstract

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 09, 2021.
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Acorde: unraveling functionally-interpretable networks of isoform co-usage from single cell data
Angeles Arzalluz-Luque, Pedro Salguero, Sonia Tarazona, Ana Conesa
bioRxiv 2021.05.07.441841; doi: https://doi.org/10.1101/2021.05.07.441841
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Acorde: unraveling functionally-interpretable networks of isoform co-usage from single cell data
Angeles Arzalluz-Luque, Pedro Salguero, Sonia Tarazona, Ana Conesa
bioRxiv 2021.05.07.441841; doi: https://doi.org/10.1101/2021.05.07.441841

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