acorde unravels functionally interpretable networks of isoform co-usage from single cell data.

acorde unravels functionally interpretable networks of isoform co-usage from single cell data.
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DOI:
10.1038/s41467-022-29497-w
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发表时间:
2022-04-05
影响因子:
16.6
通讯作者:
Conesa A
Conesa A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Arzalluz-Luque A;Salguero P;Tarazona S;Conesa A

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选择性剪接(AS)是一种高度调节的转录后机制,已知其调节基因内的异构体表达并有助于细胞类型的同一性。然而,在何种程度上替代异构体建立共表达网络,可能是相关的细胞功能尚未探索。在这里,我们介绍了acorde,一个成功利用批量长读段和单细胞数据来自信地检测替代同种型共表达关系的管道。为了实现这一目标,我们开发并验证了百分位相关性,这是一种创新的方法,可以克服数据稀疏性,并从单细胞数据中获得准确的共表达估计。接下来,acorde使用相关性将共同表达的异构体聚类到一个网络中,解开细胞类型特定的替代异构体使用模式。通过在这些簇之间选择相同的基因亚型,我们随后检测和表征跨细胞类型的具有共差异亚型使用(coDIU)的基因。最后,我们预测功能元件从长读定义的异构体,并提供深入了解生物过程,图案,和域可能控制的协调转录后调控。acorde的代码可在https://github.com/ConesaLab/acorde上获得。选择性剪接(AS)是一种高度调节的转录后机制,已知其调节基因内的异构体表达并有助于细胞类型的同一性。在这里,作者介绍了acorde,这是一个成功利用大量长读段和单细胞数据来自信地检测替代同种型共表达关系的管道。
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 be 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 develop and validate percentile correlations, an innovative 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 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. The code for acorde is available at https://github.com/ConesaLab/acorde. Alternative splicing (AS) is a highly-regulated post-transcriptional mechanism known to modulate isoform expression within genes and contribute to cell-type identity. Here, the authors present acorde, a pipeline that successfully leverages bulk long reads and single-cell data to confidently detect alternative isoform co-expression relationships.
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