Exploiting single-cell RNA sequencing data to link alternative splicing and cancer heterogeneity: A computational approach.
Int J Biochem Cell Biol
; 108: 51-60, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30633986
ABSTRACT
Cell heterogeneity studies using single-cell sequencing are gaining great significance in the era of personalized medicine. In particular, characterization of tumor heterogeneity is an emergent issue to improve clinical oncology, since both inter- and intra-tumor level heterogeneity influence the utility and application of molecular classifications through specific biomarkers. Majority of studies have exploited gene expression to discriminate cell types. However, to provide a more nuanced view of the underlying differences, isoform expression and alternative splicing events have to be analyzed in detail. In this study, we utilize publicly available single cell and bulk RNA sequencing datasets of breast cancer cells from primary tumors and immortalized cell lines. Breast cancer is very heterogeneous with well defined molecular subtypes and was therefore chosen for this study. RNA-seq data were explored in terms of genes, isoforms abundance and splicing events. The study was conducted from an average based approach (gene level expression) to detailed and deeper ones (isoforms abundance/splicing events) to perform a comparative analysis, and, thus, highlight the importance of the splicing machinery in defining the tumor heterogeneity. Moreover, here we demonstrate how the investigation of gene isoforms expression can help to identify the appropriate in vitro models. We furthermore extracted marker isoforms, and alternatively spliced genes between and within the different single cell populations to improve the classification of the breast cancer subtypes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Análise de Sequência de RNA
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Processamento Alternativo
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Biologia Computacional
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Análise de Célula Única
Limite:
Humans
Idioma:
En
Revista:
Int J Biochem Cell Biol
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália