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RNA alternative splicing (AS) is a post-transcriptional step in the regulation of eukaryotic gene expression that relies on the fine synergy of multifactorial and cis-acting elements. Its abnormalities are very common in diseases, especially in cancer. However, the identification of novel alternative splicing requires the support of relevant databases and bioinformatic analysis.
Our in-house RNA sequencing data analysis platform is dedicated to unraveling the complex mechanisms of gene regulation and solving complex biological problems.
Alternative splicing is the process of generating different mRNA splice isoforms from one mRNA precursor by different splicing methods (choosing different combinations of splice sites), so that the final protein products will exhibit different or mutually antagonistic functional and structural properties, or will be expressed at different levels in the same cell, resulting in different phenotypes.
During alternative splicing events, exons can be selectively included or eliminated, while introns can be selectively retained or sheared. Alternative splicing is an important part of the regulation of gene expression in eukaryotes, and it plays an important role in cell differentiation, growth, and signal transduction.
Splicing of mRNA precursors (pre-mRNAs) allows a single gene to generate multiple transcripts and is a major contributor to maintaining proteome diversity. There is growing evidence that aberrant splicing is associated with multiple human cancers and contributes to tumorigenesis and tumor progression by producing aberrant proteins and genetic isoforms. Therefore, the discovery of new tumor-associated AS and the exploration of detailed mechanisms of dysregulated splicing will provide effective strategies for treating tumors by correcting alternative RNA splicing.
Main types of alternative splicing events (Rosenkranz R R E et al., 2022)
Alternative splicing analysis pipeline (Albert Lahat B.Sc. et al. 2016)
Table 1 Partial software and database list
Software or database | Principle | Differential Analysis | AS Type |
---|---|---|---|
rMATS | event-based | yes | 5 |
MAJIQ | event-based | yes | 5 |
LeafCutter | intron excision | yes | Unkown |
SUPPA2 | event-based | yes | 7 |
SplAdder | event-based | yes | 5 |
Whippet | event-based | yes | 9 |
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References