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bioRxiv · 10.1101/2021.12.14.472573

Shared regulation and functional relevance of local gene co-expression revealed by single cell analysis

Ribeiro, D. M.·Ziyani, C.·Delaneau, O.
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Abstract

Most human genes are co-expressed with a nearby gene. Yet, previous studies only reported this extensive local gene co-expression using bulk RNA-seq. Here, we leverage single cell datasets in >85 individuals to identify gene co-expression across cells, unbiased by cell type heterogeneity and benefiting from the co-occurrence of transcription events in single cells. We discover thousands of co-expressed genes in two cell types and (i) compare single cell to bulk RNA-seq in identifying local gene co-expression, (ii) show that many co-expressed genes - but not the majority - are composed of functionally-related genes and (iii) provide evidence that these genes are transcribed synchronously and their co-expression is maintained up to the protein level. Finally, we identify gene-enhancer associations using multimodal single cell data, which reveal that >95% of co-expressed gene pairs share regulatory elements. Our in-depth view of local gene co-expression and regulatory element co-activity advances our understanding of the shared regulatory architecture between genes.

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Ribeiro, D. M., Ziyani, C., Delaneau, O.. 2021-12-16. Shared regulation and functional relevance of local gene co-expression revealed by single cell analysis. https://doi.org/10.1101/2021.12.14.472573

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