scAPA atlas

  Alternative polyadenylation is emerging as an important mechanism in the post-transcriptional regulation of gene expression across eukaryotic species. Recent studies have shown that APA plays key roles in diverse biological process, such as cell differentiation and cell proliferation. Notably, APA often occurs in a tissue-specific and cell-type-specific manner. The scAPAatlas is designed to explore cell-type-specific APA events across different cell types in human and mouse.

In scAPAatlas, it includes:

  • The taxonomy of cell types in different tissues;
  • The APA landscape of different cell types;
  • Cell-type-specific APA events in different tissues;
  • APA events correlated with gene expression level;
  • miRNAs binding on 3'UTR altered by cell-type-specific APA events;
  • RBPs binding on 3'UTR altered by cell-type-specific APA events.






Taxonomy
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Landscape
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Specific APA
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Expression Correlation
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miRNA & RBP-APA
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Tips: Please wait for loading, and then select the Species/Tissue/Cell Type and click the "Submit" button.



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Tips: Please wait for loading , and then select the Species and click the "Submit" button.



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Users could click the 'More' link to open a modal window incorporating the summary statistics of each module. The information of different species could be viewed by selecting human or mouse for species.

  • Taxonomy: The number of single cell per tissue.
  • Landscape: The number of identified APA events per tissue.
  • Specific APA: The number of identified cell-type-specific APA events per tissue.
  • Expression Correlation: The distribution of positively and negatively correlated genes.
  • miRNA & RBP-APA: The number of miRNAs and RBPs identified in miRNA-APA and RBP-APA modules.

Taxonomy



By selecting species and tissue, users could get a glimpse of the cell taxonomy of a certain tissue. Users not only could select the 't-SNE' panel to view the cell-type clustering of single cells, but also could select the 'Marker Gene' panel to visualize the expression of representative marker genes by dot-plot heatmaps where the color intensity represents the average level of expression and the size of dot represents the percentage of cells within each cell-type-cluster expressing the marker gene. In addition, users could select 'Summary' panel to obtain the number of single cells per cell type in the scRNA-seq dataset.

Landscape



By selecting species, entering gene symbol and selecting tissue, users could explore the APA landscape of a certain gene of different cell types within tissue or across tissues. This section provides a tabular view of of APA events. It includes:

  • Gene Symbol: Gene name of the APA event.
  • APA: The polyA site ID of the APA event, termed by Ensembl ID and the order.
  • APA Position: Genomic coordinate of the polyA site.
  • Plot: Clicking the 'Plot' button to visualize the relative usage of the polyA site (PAU) for a APA event in different cell types.

Specific APA



Users could browse, search or visualize by selecting Species/Tissue/Cell type. Besides, users could enter a gene symbol to query cell-type-specific APA patterns for a specific gene. This section provides a tabular view of of cell-type-specific APA events. It includes:

  • Cell Type: Cell type of the cell-type-specific APA event.
  • Gene Symbol: Gene name of the cell-type-specific APA event.
  • Gene Position: Genomic coordinate of the gene.
  • Specific APA: The polyA site ID of the cell-type-specific APA event, termed by Ensembl ID and the order.
  • Specific APA Position: Genomic coordinate of the polyA site.
  • PAU: The relative usage of the polyA site.
  • Difference of PAU: The difference between the largest PAU and second largest PAU across all cell types of the tissue.
  • Q-value: The FDR adjusted p-value of differential PAU across different cell types.
  • JBrowse: Clicking the 'Display' button to open a modal window implemented with a genome browser. The genome coverage tracks of different cell types are displayed with genome annotation and polyA sites annotated in scAPAatlas.

Expression Correlation



Users could browse or search APA events significantly correlated the corresponding gene expression level by selecting Species or entering gene symbol. This section provides a tabular view of of APA events correlated with gene expression level. It includes:

  • Gene Symbol: Gene name of the APA event.
  • APA: The polyA site ID of the APA event, termed by Ensembl ID and the order.
  • APA postion: Genomic coordinate of the polyA site.
  • Rs: The Spearman correlation coefficient between PAU and gene expression level.
  • P-value: The p-value of the correlation test.
  • Plot: Clicking the 'Plot' button to visualize the correlation between PAU and gene expression level.

miRNA-APA



Users could browse, search or visualize potential miRNA-binding sites on alternative regions regulated by cell-type-specific APA events in this module via selecting Species/Tissue/Cell Type and entering a gene symbol. In addition to the information of cell-type-specific APA events introduced above, the tabular view of miRNA-biding sites includes:

  • miRNA: The name of miRNA that binds on the alternative regions regulated by cell-type-specific APA events. Clicking the miRNA name will open a webpage from miRBase, incoporating the miRNA sequence, related scientific literature and word cloud representing the biological functions of the miRNA.
  • miRNA Binding Sites: Genomic coordiantes of miRNA-binding sites.
  • Score: Context++ score percentile estimated using TargetScan. A high score shows the binding site is more favorable than most other sites of this miRNA.
  • JBrowse: Clicking the 'Display' button to open a modal window implemented with a genome browser. The miRNA-binding sites are added as a genome track to visualize the crosstalk between miRNAs and cell-type-specific APA events.

RBP-APA



Users could browse, search or visualize potential RBP-binding sites on alternative regions regulated by cell-type-specific APA events in this module via selecting Species/Tissue/Cell Type and entering a gene symbol. In addition to the information of cell-type-specific APA events introduced above, the tabular view of RBP-biding sites includes:

  • RBP: The name of RBP that binds on the alternative regions regualted by cell-type-specific APA events. Clicking the RBP name will open a webpage from CISBP-RNA introducing the RBP.
  • RBP Binding Sites: Genomic coordinates of RBP-binding sites.
  • eCLIP Support: The RBP-binding sites are label with 0 or 1 for whether eCLIP-seq peaks are overlapped. This column is restricted to human data as eCLIP-seq data is only available for human in ENCODE project.
  • JBrowse: Clicking the 'Display' button to open a modal window implemented with a genome browser. The RBP-binding sites are added as a genome track to visualize the crosstalk between RBPs and cell-type-specific APA events.




About

What is scAPAatlas

Alternative polyadenylation (APA) has been widely recognized as an important mechanism in posttranscriptional regulation. Increasing studies have revealed the role of APA in several biological processes, such as cell differentiation, stress responses and proliferation. APA often occurs in a tissue-specific manner as documented in previous studies. Furthermore, recent studies have detailed the existence of cell-type-specific APA preference within the same tissue. Thus, exploration of APA at cell-type level could expand our understanding of APA, such as in cell identity determination.

To leverage the wealth of accumulated scRNA-seq, we collected and processed about 150TB 10X Genomics scRNA-seq data from 24 human and 25 mouse normal tissues, including 299 human cell types and 286 mouse cell types. We utilized the scAPA method to identify polyA sites and quantitatively infer APA at cell-type level. Thus, we could profile the APA landscape and identify cell-type-specific APA events for each cell type in a certain tissue. We also examined the correlations between APA and the corresponding gene expression level to explore the effects of polyA site choice on gene expression. In addition, the potential binding information of microRNAs (miRNAs) and RNA-binding proteins (RBPs) on alternative regions regulated by cell-type-specific APA events has been estimated. Integrating all these results, scAPAatlas is a comprehensive resource designed for users to explore APA at cell-type level and elucidate biological functions of APA.

In scAPAatlas, users can:

Get a glimpse of the taxonomy of cell types in different tissues
Explore the APA landscape of different cell types within tissue or across tissues
Browse, search or visualize cell-type-specific APA events in different tissues
Browse, search or visualize APA events correlated with gene expression level
Browse, search or visualize miRNA-binding sites to explore crosstalk between miRNA and APA events
Browse, search or visualize RBP-binding sites to explore crosstalk between RBP and APA events
Download all the tables and figures.

The pipeline of database construction

The data resources used in scAPAatlas

Acknowledgements

The scAPAatlas was construted using R package shiny-server. R packages shinydashboard, shinythemes, dashboardthemes, shinyBS, shinyjs, shinybusy were used in interactive interface design. The R package DT which provides an R interface to the JavaScript library DataTables were applied to display tables. The R package JBrowseR were used to display genomic data.

How to cite

scAPAatlas: An atlas of alternative polyadenylation across cell types in human and mouse

Xiaoxiao Yang, Yang Tong, Gerui Liu, Jiapei Yuan, Yang Yang (2021). Nucleic Acids Res., gkab917




Contact Information

Yang Yang (Corresponding Author)

Email: yy(AT)tmu.edu.cn

 

Xiaoxiao Yang (First Author)

Email:Yangxx(AT)tmu.edu.cn

Yang Tong (First Author)

Email:Tyang(AT)tmu.edu.cn

 

Affilation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University

Address: 22 Qixiangtai Road, Heping District, Tianjin 300070, China

Any comments or suggestion are welcome to improve scAPAatlas.

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