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SCAPE: a mixture model revealing single-cell polyadenylation diversity and cellular dynamics during cell
Ran Zhou1, Xia Xiao1, Ping He1
1Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Nucleic Acids Research
|March 15, 2022
Summary
This study introduces SCAPE, a Bayesian method for identifying and quantifying polyadenylation (pA) sites in single cells. SCAPE reveals novel pA sites and their dynamic regulation, offering insights into cellular diversity and function.
Area of Science:
- Molecular Biology
- Genomics
- Bioinformatics
Background:
- Alternative polyadenylation (APA) generates transcript diversity, impacting crucial biological processes like cell differentiation and cancer.
- Understanding APA at the single-cell level is essential for deciphering cellular heterogeneity and function.
Purpose of the Study:
- To develop a novel Bayesian method, SCAPE, for de novo identification and quantification of polyadenylation (pA) sites at the single-cell level.
- To explore the role of APA isoforms in tissue-specific regulation, miRNA binding, and cellular dynamics during differentiation.
Main Methods:
- Development of SCAPE, a Bayesian approach utilizing insert size information for single-cell polyadenylation site analysis.
- Application of SCAPE to analyze polyadenylation sites across 36 mouse organs.
Main Results:
- Identification of 31,558 polyadenylation sites, with 43.8% being novel.
- Demonstration that APA isoforms are regulated in tissue-, cell type-, and tumor-specific manners, independent of gene expression levels.
- Observation of dynamic, genome-wide changes in APA usage during erythropoiesis and induced pluripotent stem cell (iPSC) differentiation.
Conclusions:
- SCAPE provides an accurate and robust method for single-cell polyadenylation site analysis.
- APA isoforms offer an additional layer of regulatory information for cell clustering and understanding cellular dynamics.
- APA plays a significant role in the functional flexibility and diversity of single cells in both health and disease.
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