Comprehensive Overview of Computational Tools for Alternative Splicing Analysis

Abstract

Alternative splicing (AS) is a fundamental mechanism that generates transcriptomic diversity by selectively including or excluding exons and introns from pre-mRNA transcripts, leading to the production of multiple protein isoforms from a single gene. This process plays a crucial role in cellular differentiation, tissue specificity, and response to environmental stimuli. Given that it enables organisms to adapt to varying conditions and maintain homeostasis, AS has become a pivotal area of study in molecular biology. The advancement of RNA-sequencing (RNA-seq) technologies has propelled the development of sophisticated tools designed to detect and analyze various AS events. These tools have become indispensable for researchers seeking to unravel the complexities of AS and its implications in health and disease. In this review, we delve into the prominent alternative splicing analysis tools rMATS, SUPPA2, LeafCutter, MISO, DEXSeq, MAJIQ, StringTie, and Cufflinks, discussing their strengths, limitations, and practical usability. Each of these tools offers unique functionalities tailored to different aspects of AS analysis, and their usefulness varies depending on computational requirements, ease of use, and the specificity of the AS events they detect. Through careful consideration of the functionalities and limitations of these tools, we offer insights into the biological contexts for which they might be best suited for AS analysis. This article is categorized under: RNA Methods > RNA Analyses In Vitro and In Silico RNA Processing > Splicing Regulation/Alternative Splicing.